Search

Objective: To investigate the safety and efficacy of the combination of radiofrequency ablation (RFA) and vertebroplasty versus single vertebroplasty in treating spinal metastases. Materials and methods: The data of 35 patients with vertebral neoplastic lesions who received RFA combined with vertebroplasty (group A, 15 patients with 17 lesions) or single vertebroplasty (group B, 20 patients with 24 lesions) from March 2016 to June 2019 were retrospectively compared. The data of patients' Visual Analogue Scale (VAS) scores prior to the treatments, 1 week, 1 month, 3 months, and 6 months after the treatments, injected cement volume, ratios of cement leakage were compared between the two groups. Results: All procedures were successfully done without severe complications. The VAS scores in group A were decreased more rapidly 1 week after the treatments and remained more stable at 6 months than that in group B (P < 0.05). The cement injected in group A (5.95 ± 1.45 mL, range 4–9.5 mL) was significantly more than that in group B (4.09 ± 0.55 mL, range 3.1–5.5 mL) (P < 0.05). The ratio of vascular cement leakage in group A was significantly lower than that in group B (P < 0.05), while no statistical difference was found in the non-vascular cement leakage (P > 0.05). Conclusions: Our study shows that the combination of RFA and vertebroplasty has a better analgesic effect with more injected cement and lower rates of venous cement leakage than single vertebroplasty. [ABSTRACT FROM AUTHOR]

Lead zirconate titanate (PZT) films have been deposited on Ti–Pt/Ti/SiO 2 /Si(100) alloy substrates by sol-gel process. The purpose of the present study was to examine the Ti content in the Ti–Pt alloy layers-dependent preferred orientation and electrical behaviors of PZT films. X-ray diffraction (XRD) shows that Ti–Pt alloy electrodes induces texture transition from (100) to (111), and the maximum peak of (100) and minimum peak of (111) are obtained in the sample on Ti–Pt alloy layer with a sputtering power of 12.5 W/150 W. The film deposited on Ti–Pt alloy layer with a sputtering power of 12.5 W/150 W exhibits a reduced oxygen vacancies concentration, which results in a maximum ε of 1224.25, an enhanced 2 P r of 40.5 μC/cm2, and a relative decreased 2 E c of 108 kV/cm. Therefore, it can be concluded that the Ti–Pt alloy layers with an appropriate Ti content play a very critical role for the preferred orientation, microstructure, and improved electrical properties of the PZT films. [ABSTRACT FROM AUTHOR]

The base sequence of nucleic acid encodes structural and functional properties into the biopolymer. Structural information includes the formation of duplexes, G-quadruplexes, i-motif, and cooperatively stabilized assemblies. Functional information encoded in the base sequence involves the strand-displacement process, the recognition properties by aptamers, and the catalytic functions of DNAzymes. This Review addresses the implementation of the information encoded in nucleic acids to develop DNA switches. A DNA switch is a supramolecular nucleic acid assembly that undergoes cyclic, switchable, transitions between two distinct states in the presence of appropriate triggers and counter triggers, such as pH value, metal ions/ligands, photonic and electrical stimuli. Applications of switchable DNA systems to tailor switchable DNA hydrogels, for the controlled drug-release and for the activation of switchable enzyme cascades, are described, and future perspectives of the systems are addressed. [ABSTRACT FROM AUTHOR]

Die Basensequenz der Nukleinsäuren verschlüsselt strukturelle und funktionelle Eigenschaften in einem Biopolymer. Strukturelle Informationen beinhalten die Bildung von Duplexen, G ‐ Quadruplexen, i ‐ Motiven und kooperativ stabilisierten Anordnungen. Funktionelle Informationen betreffen z. B. den Prozess der Strangverdrängung, Erkennungseigenschaften von Aptameren und die katalytische Funktion von DNAzymen. Dieser Aufsatz befasst sich mit der Implementierung der in Nukleinsäuren kodierten Informationen zur Entwicklung von DNA ‐ Schaltern. Ein DNA ‐ Schalter ist eine supramolekulare Nukleinsäureanordnung, die in Gegenwart geeigneter Auslöser und Gegenauslöser wie pH, Metallionen/Liganden, photonischen und elektrischen Stimuli zyklische, schaltbare Übergänge zwischen zwei Zuständen eingeht. Anwendungen von schaltbaren DNA ‐ Systemen umfassen maßgeschneiderte DNA ‐ Hydrogele für die kontrollierte Wirkstofffreisetzung und die Aktivierung schaltbarer Enzymkaskaden. Intelligente DNA: Die reizgesteuerte, reversible Rekonfiguration von i ‐ Motiven, G ‐ Quadruplexen und Duplex ‐ DNA ‐ Strukturen oder von DNA ‐ Bausteinen wie Pinzetten, Nanofedern und Walkern ist die Grundlage für die Entwicklung schaltbarer DNA ‐ Nanostrukturen mit Auslösern wie pH ‐ Wert, Metallionen oder elektrochemischen Signalen. Potenzielle Anwendungen von DNA ‐ Schaltern umfassen die kontrollierte Wirkstoff ‐ Freisetzung, das Öffnen/Schließen von Poren und schaltbare Katalyse. [ABSTRACT FROM AUTHOR]

Mimicking cellular transformations and signal transduction pathways by means of biocatalytic cascades proceeding in organized media is a scientific challenge. We describe two DNA machines that enable the 'ON/OFF' switchable activation and deactivation of three-component biocatalytic cascades. One system consists of a reconfigurable DNA tweezers-type structure, whereas in the second system the catalytic cascade proceeds on a switchable DNA clamp scaffold. The three-component catalytic cascades consist of β-galactosidase (β-Gal), glucose oxidase (GOx), and the K+-ion-stabilized hemin-G-quadruplex horseradish peroxidase (HRP)-mimicking DNAzyme. The hemin-G-quadruplex-bridged closed structure of the tweezers or clamp allows the biocatalytic cascades to operate (switched 'ON′′), whereas separation of the hemin-G-quadruplex by means of 18-crown-6-ether opens the tweezers/clamp structures, thus blocking the catalytic cascade (switched 'OFF'). This study is complemented by two-component, switchable biocatalytic cascades composed of GOx and hemin-G-quadruplex assembled on hairpin-bridged DNA tweezers or clamp nanostructures. [ABSTRACT FROM AUTHOR]

The K+-induced formation of G-quadruplexes provides a versatile motif to lock or unlock substrates trapped in the pores of mesoporous SiO2 nanoparticles, MP-SiO2 NPs. In one system, the substrate is locked in the MP-SiO2 NPs by K+-ion-stabilized G-quadruplex units, and the pores are unlocked by the elimination of K+ ions using Kryptofix [2.2.2] (KP) or 18-crown-6-ether (CE) from the G-quadruplexes. In the second system, the substrate is locked in the pores by means of K+-stabilized aptameric G-quadruplex/thrombin units. Unlocking of the pores is triggered by the dissociation of the aptamer/thrombin complexes through the KP- or CE-mediated elimination of the stabilizing K+ ions. In the third system, duplex DNA units lock the pores of MP-SiO2 NPs, and the release of the entrapped substrate is stimulated by the K+-ion-induced dissociation of the duplex caps through the formation of the K+-stabilized G-quadruplexes. The latter system is further implemented to release the anti-cancer drug, doxorubicin, in the presence of K+ ions, from the MP-SiO2 NPs. Preliminary intracellular experiments reveal that doxorubicin-loaded MP-SiO2 NPs lead to effective death of breast cancer cells. [ABSTRACT FROM AUTHOR]

The information encoded in the base sequence of DNA provides substantial structural and functional information for the instructive self-assembly of one-dimensional (1D) functional DNA nanostructures. The hybridization chain reaction (HCR) and the formation of HCR-stimulated DNAzyme nanochains are presented, as a means to develop amplified DNA sensors and aptasensors. Similarly, the rolling circle amplification (RCA) process is implemented to generate 1D DNA nanochains consisting of constant repeat units being implemented for the amplified sensing (using DNAzymes as repeat units) and for the switchable control of electron transfer at electrodes. 1D DNA nanostructures are used as templates for the programmed positioning of enzymes that enable the activation of enzyme cascades and the biocatalytic growth of metallic nanowires. The future perspectives of the self-assembly mechanisms are discussed. [ABSTRACT FROM AUTHOR]

Radiofrequency ablation (RFA) is a common minimally invasive treatment for hepatocellular carcinoma (HCC). Incomplete RFA (iRFA) due to the sub-lethal heat shock challenge of some cell populations leads to the generation of transformed survivor cells with enhanced chemoresistance. However, the underlying mechanism of iRFA on HCCs chemoresistance remains unknown. In the present study, we investigated the effect of iRFA on HCCs sensitivity to cisplatin. Cells treated with the sub-lethal heat shock challenge were used to mimic iRFA treatment in vitro. An orthotopic implantation HCC model was established and also performed iRFA treatment. Flow cytometry, transwell assay, and cell counting kit-8 assay were used to determine the effect of iRFA treatment on cisplatin-induced HCC cell apoptosis, invasion, and cell viability. ELISA and Western blot were used to detect the effect of iRFA treatment on cisplatin-induced HCC cell pyroptosis. We found that iRFA treatment increased the HCC cell proliferation and invasion ability, and inhibited cisplatin-induced pyroptosis. Further experiments showed that iRFA treatment induced upregulation of HSP70, which inhibited the cisplatin-induced NLRP3 inflammasome activation, leading to inhibition of pyroptosis. HSP70 knockdown or NLRP3 overexpression could reverse the effect of iRFA treatment in vitro. In vivo , HSP70 knockdown reversed the chemosensitivity of HCC to cisplatin, which was decreased by iRFA. In conclusion, we demonstrated that iRFA induced drug resistance by HSP70-mediated inhibition of cell pyroptosis in HCC. • iRFA treatment inhibited cisplatin-induced pyroptosis of HCC cells. • Heat shock protein 70 was involved in the suppression of NLRP3 activation. • iRFA treatment decreased the cisplatin sensitivity of HCC through regulating HSP70. [ABSTRACT FROM AUTHOR]

The Cu2+-dependent ligation DNAzyme is implemented as a biocatalyst for the colorimetric or chemiluminescence detection of Cu2+ ions, Hg2+ ions, or cocaine. These sensing platforms are based on the structural tailoring of the sequence of the Cu2+-dependent ligation DNAzyme for specific analytes. The tethering of a subunit of the hemin/G-quadruplex DNAzyme to the ligation DNAzyme sequence, and the incorporation of an imidazole-functionalized nucleic-acid sequence, which acts as a co-substrate for the ligation DNAzyme that is tethered to the complementary hemin/G-quadruplex subunit. In the presence of different analytes, Cu2+ ions, Hg2+ ions, or cocaine, the pretailored Cu2+-dependent ligation DNAzyme sequence stimulates the respective ligation process by combining the imidazole-functionalized co-substrate with the ligation DNAzyme sequence. These reactions lead to the self-assembly of stable hemin/G-quadruplex DNAzyme nanostructures that enable the colorimetric analysis of the substrate through the DNAzyme-catalyzed oxidation of 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid), ABTS2−, by H2O2 into the colored product ABTS.−, or the chemiluminescence detection of the substrate through the DNAzyme-catalyzed oxidation of luminol by H2O2. The detection limits for the sensing of Cu2+ ions, Hg2+ ions, and cocaine correspond to 1 n M, 10 n M and 2.5 μ M, respectively. These different sensing platforms also reveal impressive selectivities. [ABSTRACT FROM AUTHOR]

Abstract: The present paper is the first report on an enzymatic logic gates system based on oxygen-controlled biofuel cell (BFC). By accepting dual gas-input signals and resulting in the maximum power output changes of the compartmentless BFC with bioanode/biocathode-immobilized enzymes, such system permits AND and XNOR Boolean logic gates readily achieved, reset and interconverted into each other in “one pot”. On the basis of the built-in Boolean XNOR logic, the proof-of-concept oxygen-controlled biocomputing system with miniature BFC operating in serum enabled us to construct a potential self-powered and implantable medical system with the diagnosis aim, which could intellectually make logic decisions that whether the dissolved oxygen content in body fluid is within normal limits or not. [Copyright &y& Elsevier]

Abstract: A method to fabricate AuAg bimetallic nanoparticles film by H2O2-mediated reduction of silver was reported. Gold nanoparticles (Au NPs) were first adsorbed onto the surface of a self-assembled 2-aminoethanethiol monolayer-modified gold film or 3-aminopropyltriethoxysilane (APTES) monolayer-modified quartz slide. Upon further treatment of this modified film with the solution containing silver nitrate (AgNO3) and H2O2, silver was deposited on the surface of Au NPs. The size of the AuAg bimetallic particles could be readily tuned by manipulating the concentration of H2O2. Surface plasmon resonance (SPR) was used to investigate the process, the deposition of silver on Au NPs modified gold film resulted in an obvious decrease of depth in the SPR reflectance intensity and minimum angle curves (SPR R-θ curves), which may be utilized for the quantitative SPR detection of the analyte, H2O2. Combination of the biocatalytic reaction that could yield H2O2 by using the enzyme, glucose oxidase, with the deposition of silver may enable the design of a glucose biosensor by SPR technique. Furthermore, we evaluated the AuAg bimetallic nanoparticles film for their ability to be an effective substrate for surface-enhanced Raman scattering (SERS). [Copyright &y& Elsevier]

Abstract: Poxviruses currently are known to disrupt Jak-STAT signal transduction induced by interferon (IFN) through two distinct mechanisms: (1) secreted poxviral IFN decoy receptors that prevent the initiation of IFN signaling from type I or II receptors at the cell surface; and (2) poxviral phosphatase that dephosphorylates STAT1 intracellularly. Here, we report a novel mechanism by which poxviruses can inhibit Jak-STAT signaling in response to type I IFN. Myxoma virus (MV) is a highly species-restricted member of the poxvirus family that infects only rabbits under the natural setting. Interestingly, primary human fibroblasts support a permissive MV infection that is only partially sensitive to the antiviral state induced by type I IFN. In this study we show that when type I IFN is added to primary human fibroblasts following MV infection, the tyrosine phosphorylation of the Janus kinase Tyk2 is specifically blocked, thereby preventing the subsequent activation of downstream STAT1 and STAT2. In stark contrast, type II IFN-induced activation of Jak1, Jak2 and STAT1 remains largely unaffected in MV-infected human fibroblasts. Unlike the de-activation of STAT1 by the poxvirus phosphatase, which is delivered into the cell by the input virions, the Tyk2 inhibition by MV infection requires new viral gene expression. Thus, our study documents a previously unrecognized immune evasion mechanism exploited by a poxvirus to selectively disrupt the type I IFN-Jak-STAT signaling cascade. [Copyright &y& Elsevier]

Abstract: In this paper, a simple, label-free and regenerative method was proposed to study the interaction between aptamer and small molecule by using methylene blue (MB+) as an electrochemical indicator. A thiolated capture probe containing twelve bases was firstly self-assembled on gold electrode by gold–sulfur affinity. Aptamer probe containing thirty two bases, which was designed to hybridize with capture DNA sequence and specifically recognize adenosine, was then immobilized on the electrode surface by hybridization reaction. MB+ was abundantly adsorbed on the aptamer probe by the specific interaction between MB+ and guanine base in aptamer probe. MB+-anchored aptamer probe can be forced to dissociate from the sensing interface after adenosine triggered structure switching of the aptamer. The peak current of MB+ linearly decreased with the concentration of adenosine over a range of 2×10−8–2×10−6 M with a detection limit of 1×10−8 M. In addition, we examined the selectivity of this electrochemical biosensor for cytidine, uridine and guanosine that belonged to the nucleosides family and possessed a similar structure with adenosine. The peak current of MB+ slightly decreased even then 1mM cytidine, uridine or guanosine was added to reaction cell for 2h, which confirmed this biosensor had a good selectivity for adenosine. After each of detection, the electrode was immersed into aptamer solution for regeneration. The recovery of the electrochemical signal of MB+ indicated the sensor surface of electrode was successfully regenerated. [Copyright &y& Elsevier]

Abstract: This paper reports the study of protein conformational change by Au nanoparticles (AuNPs)-amplified surface plasmon resonance (SPR) spectroscopy. Taking cytochrome c (Cyt c) as an example, this paper gives a detailed description of the construction of metal–protein–metal sandwich nanostructure consisting of an Au film underlayer, a cytochrome c intermediate layer and an AuNPs upper layer. The incorporation of AuNPs into SPR biosensing results in increased SPR sensitivity to protein conformational change as demonstrated by acid denaturation of Cyt c. It suggests the conformational change of surface-confined Cyt c leads to the distance and electromagnetic coupling variations of Au film–AuNPs. The constructed Au film–Cyt c–AuNPs sandwich is stable to repeat acid treatment using solutions in the pH range of 2.0–10.0 and yields reproducible measurements. With high sensitivity and stability, nanoparticle-amplified SPR spectroscopy can be used as a supplement method to protein conformational study. It has potential for developing novel sensors and/or switching devices in response to protein conformational change. [Copyright &y& Elsevier]

Abstract: In this work, we illustrate a simple chelation-based strategy to trigger DNA release from DNA-incorporated multilayer films, which were fabricated through the layer-by-layer (LbL) assembly of DNA and inorganic zirconium (IV) ion (Zr4+). After being incubated in several kinds of chelator solutions, the DNA multilayer films disassembled and released the incorporated DNA. This was most probably due to the cleavage of coordination/electrostatic interactions between Zr4+ and phosphate groups of DNA. Surface plasmon resonance (SPR), UV–vis spectrometry and atomic force microscopy (AFM) were used to characterize the assembly and the disassembly of the films. By incorporating plasmid DNA (pDNA) into this controllable disassembly system, the multilayer films sustained the consecutive DNA release. The released pDNA retained its integrity and transcriptional activity, and also expressed enhanced green fluorescent protein (EGFP) after being transfected into HEK 293 cells. Besides the simplicity and cost efficiency of this method, the most advantage of this route was that the release of DNA from the films could be modulated by various external conditions, such as the chelator and ionic strength. The Zr4+/DNA multilayer films with the ability to precisely control the release rate of DNA might serve as an alternative localized gene delivery system in the perspective of biomedical applications. [Copyright &y& Elsevier]

Abstract: A one-compartment glucose/O2 biofuel cell based on an electrostatic layer-by-layer (LbL) technique on three-dimensional ordered macroporous (3DOM) gold electrode was described. A 3DOM gold electrode was synthesized electrochemically by an inverted colloidal crystal template technique. Then the macroporous gold electrodes were functionalized with Au nanoparticles (AuNPs) and enzyme, glucose dehydrogenase (GDH) or laccase. The (AuNPs/GDH) n multilayer modified macroporous gold electrode showed excellent bioelectrocatalytic activity towards glucose. The direct electroreduction towards oxygen was realized at (AuNPs/laccase) n films on 3DOM gold electrodes. The maximum power density of the cell with the macroporous film as matrix was 178μWcm−2 at 226mV, which was 16 times larger than that of the biofuel cell with the flat electrode under the same condition. The proposed method is simple and would be applicable to enhance the power output of miniaturized biofuel cell. [Copyright &y& Elsevier]

Abstract: We described the use of silica nanoparticles as building blocks for the immobilization of electrogenerated chemiluminescence (ECL) reagent Ru(bpy)3 2+ and the fabrication of layer-by-layer assembly film by alternating the deposition of the Ru(bpy)3 2+-doped silica nanoparticles and Au nanoparticles. UV–vis absorption spectroscopy, scanning electron microscopy (SEM), cyclic voltammetry and ECL were used to characterize the uniform growth of the multilayer film. Since Ru(bpy)3 2+ could still maintain its ECL property when doped into the silica nanoparticles, the as-prepared multilayer film could be used as an effective ECL sensor, and the sensor showed high sensitivity and good stability. [Copyright &y& Elsevier]

Abstract: In this paper, electrochemical surface plasmon resonance (SPR) method was first used to detect enzymatic reaction in bilayer lipid membrane (BLM) based on immobilizing horseradish peroxidase (HRP) in the BLMs supported by the redox polyaniline (PAn) film. By SPR kinetic curve in situ monitoring the redox transformation of PAn film resulted from the reaction between HRP and PAn, the enzymatic reaction of HRP with H2O2 was successfully analyzed by electrochemical SPR spectroscopy. The results show that this BLM supported on PAn film cannot only preserve the bioactivity of HRP immobilized in the membrane, but also provide a channel for the transfer of electrons between HRP and PAn on electrode surface. These characteristics enabled the development of SPR biosensor for sensitively detecting H2O2. H2O2 has been detected by electrochemical SPR spectroscopy in the concentration range of 5×10−5 M to 2×10−3 M. After each of detections, the SPR sensor surface was completely regenerated by electrochemically reducing the oxidized PAn to its reduced state. This method provides a novel route for enhancing the detection of small ligand of enzymatic reaction in BLM by electrochemical SPR spectroscopy. [Copyright &y& Elsevier]

Abstract: Through electrostatic layer-by-layer (LbL) assembly, negatively charged calf thymus double stranded DNA (CTds-DNA), and positively charged Zr4+ ions were alternately deposited on gold substrate modified with chemisorbed cysteamine. Thus-prepared three-dimensional DNA networks were characterized by surface plasmon resonance (SPR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and infrared reflection–absorption spectroscopy (IR-RAS). SPR spectroscopy indicates that the effective thickness of DNA monolayer in the (DNA/Zr4+)1 bilayer was 1.5±0.1nm, which corresponds to the surface coverage of 79% of its full packed monolayer. At the same time, a linear increase of film thickness with increasing number of layers was also confirmed by SPR characterizations. The data of XPS and IR-RAS show that Zr4+ ions interact with both the phosphate groups and nitrogenous bases of DNA and load into the framework of DNA. Furthermore, the interactions between this composite film and heme protein cytochrome c (Cyt c) were investigated by SPR spectroscopy and electrochemistry. Compared with the adsorption of Cyt c on DNA monolayer, this composite multilayer film can obviously enhance the amount of immobilized Cyt c confirmed by SPR reflectivity-incident angle (R-θ) curves. Cyclic voltammetry (CV) indicates the Cyt c adsorbed on the composite film is electroactive, and the enhancement of peak current in CV indirectly verifies the increase of the amount of immobilized Cyt c. [Copyright &y& Elsevier]

Abstract: Gold nanoparticles were deposited onto 2-mercaptoethylamine (MEA)-assembled planar gold thin film to construct gold nanoparticles modified electrode by virtue of a solution-based self-assembly strategy. Subsequently, 3-mercaptopropionic acid (MPA)-bridged copper hexacyanoferrate (CuHCF) multilayers were constructed on the as-prepared gold nanoparticles modified electrode. The resulted multilayer nanostructures were investigated by electrochemical surface plasmon resonance (EC-SPR) and atomic force microscopy (AFM) with primary emphasis upon the effect of the gold nanoparticles on the MPA/CuHCF multilayers growth and their surface morphology. Compared with the multilayer system on a planar gold electrode, the different electrochemical and optical properties might result from higher curvature effect and extraordinary surface-to-volume ratio characteristic of gold nanoparticles and the nanoparticle-selective growth of CuHCF. A dendrimer-like assembly process was proposed to explain the experiment results. This new motif of multilayer on the gold nanoparticles modified electrode was different from that of on a planar gold electrode, indicating a potential application of EC-SPR technique in the study of nanocomposite materials. [Copyright &y& Elsevier]

Abstract: Small molecules are difficult to detect by conventional surface plasmon resonance (SPR) spectroscopy due to the fact that the changes in the refractive index resulted from the binding process of small biomolecules are quite small. Here, we report a simple and effective method to detect small biomolecule using SPR spectroscopy and electrochemistry by catalyzed deposition of metal ions on SPR gold film. As an example, the ascorbic acid-mediated deposition of Ag on gold film was monitored by in situ SPR spectrum. The deposition of Ag atom on gold film resulted in an obvious decrease of depth in SPR angular scan curves of reflectance intensity and minimum reflectivity angle. The depth change of the SPR reflectance intensity and minimum reflectivity angle curves mainly relied on the amount of Ag atom deposited on gold film that can be controlled by the concentration of ascorbic acid. By monitoring the deposition of Ag atom on gold film, ascorbic acid was detected in the concentration range of 2×10−5 M to 1× 10−3 M. After each of detections, the SPR sensor surface was completely regenerated by a potential step that stripped off the Ag atom. Furthermore, the regeneration process of the sensor surface provides the feasibility for detecting the concentration of ascorbic acid by electrochemical method. [Copyright &y& Elsevier]

Myxoma virus, a member of the poxvirus family, causes lethal infection only in rabbits, but the mechanism underlying the strict myxoma virus species barrier is not known. Here we show that myxoma virus infection of primary mouse embryo fibroblasts elicited extracellular signal-regulated kinase (Erk) signaling, which was integrated to interferon regulatory factor 3 activation and type I interferon induction. We further show that Erk inactivation or disruption of interferon signaling mediated by the transcription factor STAT1 broke the cellular blockade to myxoma virus multiplication. Moreover, STAT1 deficiency rendered mice highly susceptible to lethal myxoma virus infection. Thus, the Erk-interferon-STAT1 signaling cascade elicited by myxoma virus in nonpermissive primary mouse embryo fibroblasts mediates an innate cellular barrier to poxvirus infection. [ABSTRACT FROM AUTHOR]

Synthetic biochemical circuits (e.g., DNA circuits) remain at the forefront of intracellular biosensing tasks yet are hindered by the undesired off‐site activation and the accompanying signal leakage. Herein, the study attempts to overcome this limitation by developing a simple‐yet‐powerful endogenous glutathione (GSH)‐regulating tactic that permits robust and distinguishable on‐site microRNA (miRNA) imaging under disturbed redox homeostasis. Specifically, a hierarchically activated catalytic DNA (HAD) circuit is fabricated by grafting the disulfide linkage within entropy‐driven DNA circuitry (EDC) reactants. It is exemplified that this HAD system promises the spatiotemporally selective microRNA‐21 (miR‐21) imaging in living cells and the robust differentiation of tumor cells from normal cells. The correlationship between GSH and miRNA is extensively explored in live cells, and can substantially expand the toolbox of DNA circuits for profiling intracellular biochemical processes. [ABSTRACT FROM AUTHOR]

The precise regulation of cellular behaviors within a confined, crowded intracellular environment is highly amenable in diagnostics and therapeutics. While synthetic circuitry system through a concatenated chemical reaction network has rarely been reported to mimic dynamic self‐assembly system. Herein, a catalytic self‐defined circuit (CSC) for the hierarchically concatenated assembly of DNA domino nanostructures is engineered. By incorporating pre‐sealed symmetrical fragments into the preying hairpin reactants, the CSC system allows the hierarchical DNA self‐assembly via a microRNA (miRNA)‐powered self‐sorting catalytic hybridization reaction. With minimal strand complexity, this self‐sustainable CSC system streamlined the circuit component and achieved localization‐intensified cascaded signal amplification. Profiting from the self‐adaptively concatenated hybridization reaction, a reliable and robust method has been achieved for discriminating carcinoma tissues from the corresponding para‐carcinoma tissues. The CSC‐sustained self‐assembly strategy provides a comprehensive and smart toolbox for organizing various hierarchical DNA nanostructures, which may facilitate more insights for clinical diagnosis and therapeutic assessment. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A label‐free deoxyribozyme (DNAzyme) biosensor for m6A demethylase activity detection is developed. When demethylase FTO (Fat mass and obesity‐associated protein), an important m6A demethylase of ALKBH demethylase family is present, the m6A 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. [ABSTRACT FROM AUTHOR]

The platelet isoform of phosphofructokinase (PFKP) is a rate-limiting enzyme involved in glycolysis that serves an important role in various types of cancer. The aim of the present study was to explore the specific regulatory relationship between PFKP and non-small cell lung cancer (NSCLC) progression. PFKP expression in NSCLC tissues and corresponding adjacent tissues was detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical analysis. PFKP expression in human bronchial epithelial cells (16HBE) and NSCLC cells (H1299, H23 and A549) was also detected using RT-qPCR. Cell proliferation was detected by Cell Counting Kit-8 and colony formation assays. Transwell invasion and wound healing assays, and flow cytometry were used to detect cell invasion, migration and apoptosis, respectively. The expression levels of glycolysis-associated enzymes (hexokinase-2, lactate dehydrogenase A and glucose transporter-1), epithelial-mesenchymal transition-related proteins (N-cadherin, vimentin and E-cadherin) and apoptosis-related proteins (caspase-3 and B-cell lymphoma-2) were detected by western blotting. Glucose uptake, lactate production and the adenosine trisphosphate/adenosine diphosphate ratio were measured using the corresponding kits. The results of the present study demonstrated that PFKP expression was upregulated in NSCLC tissues and cells, and PFKP expression was related to lymph node metastasis and histological grade. In addition, overexpression of PFKP inhibited cell apoptosis, and promoted proliferation, migration, invasion and glycolysis of H1299 cells, whereas knockdown of PFKP had the opposite effects. In conclusion, PFKP inhibited cell apoptosis, and promoted proliferation, migration, invasion and glycolysis of NSCLC cells; these findings may lay the foundation for novel treatments of NSCLC. [ABSTRACT FROM AUTHOR]

A versatile approach for the fine control of DNA-based hierarchical assembly via dual stimuli and two assembly strategies is developed. Moreover, with a reasonable design of functional thrombin aptamer structures on the formed DNA nanoassembly, it can achieve precise regulation of thrombin activity. [ABSTRACT FROM AUTHOR]

Nucleic acids in biofluids are emerging biomarkers for the molecular diagnostics of diseases, but their clinical use has been hindered by the lack of sensitive detection assays. Herein, we report the development of a sensitive nucleic acid detection assay named SPOT (sensitive loop‐initiated DNAzyme biosensor for nucleic acid detection) by rationally designing a catalytic DNAzyme of endonuclease capability into a unified one‐stranded allosteric biosensor. SPOT is activated once a nucleic acid target of a specific sequence binds to its allosteric module to enable continuous cleavage of molecular reporters. SPOT provides a highly robust platform for sensitive, convenient and cost‐effective detection of low‐abundance nucleic acids. For clinical validation, we demonstrated that SPOT could detect serum miRNAs for the diagnostics of breast cancer, gastric cancer and prostate cancer. Furthermore, SPOT exhibits potent detection performance over SARS‐CoV‐2 RNA from clinical swabs with high sensitivity and specificity. Finally, SPOT is compatible with point‐of‐care testing modalities such as lateral flow assays. Hence, we envision that SPOT may serve as a robust assay for the sensitive detection of a variety of nucleic acid targets enabling molecular diagnostics in clinics. [ABSTRACT FROM AUTHOR]

Nucleic acids in biofluids are emerging biomarkers for the molecular diagnostics of diseases, but their clinical use has been hindered by the lack of sensitive detection assays. Herein, we report the development of a sensitive nucleic acid detection assay named SPOT (sensitive loop‐initiated DNAzyme biosensor for nucleic acid detection) by rationally designing a catalytic DNAzyme of endonuclease capability into a unified one‐stranded allosteric biosensor. SPOT is activated once a nucleic acid target of a specific sequence binds to its allosteric module to enable continuous cleavage of molecular reporters. SPOT provides a highly robust platform for sensitive, convenient and cost‐effective detection of low‐abundance nucleic acids. For clinical validation, we demonstrated that SPOT could detect serum miRNAs for the diagnostics of breast cancer, gastric cancer and prostate cancer. Furthermore, SPOT exhibits potent detection performance over SARS‐CoV‐2 RNA from clinical swabs with high sensitivity and specificity. Finally, SPOT is compatible with point‐of‐care testing modalities such as lateral flow assays. Hence, we envision that SPOT may serve as a robust assay for the sensitive detection of a variety of nucleic acid targets enabling molecular diagnostics in clinics. [ABSTRACT FROM AUTHOR]

Background: Lipid pathways play a crucial role in psoriatic arthritis development, and some lipid-lowering drugs are believed to have therapeutic benefits due to their anti-inflammatory properties. Traditional observational studies face issues with confounding factors, complicating the interpretation of causality. This study seeks to determine the genetic link between these medications and the risk of psoriatic arthritis. Methods: This drug target study utilized the Mendelian randomization strategy. We harnessed high-quality data from population-level genome-wide association studies sourced from the UK Biobank and FinnGen databases. The inverse variance-weighted method, complemented by robust pleiotropy methods, was employed. We examined the causal relationships between three lipid-lowering agents and psoriatic arthritis to unveil the underlying mechanisms. Results: A significant association was observed between genetically represented proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition and a decreased risk of psoriatic arthritis (odds ratio [OR]: 0.51; 95% CI 0.14–0.88; P < 0.01). This association was further corroborated in an independent dataset (OR 0.60; 95% CI 0.25–0.94; P = 0.03). Sensitivity analyses affirmed the absence of statistical evidence for pleiotropic or genetic confounding biases. However, no substantial associations were identified for either 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors or Niemann–Pick C1-like 1 inhibitors. Conclusions: This Mendelian randomization analysis underscores the pivotal role of PCSK9 in the etiology of psoriatic arthritis. Inhibition of PCSK9 is associated with reduced psoriatic arthritis risk, highlighting the potential therapeutic benefits of existing PCSK9 inhibitors. [ABSTRACT FROM AUTHOR]

The progression of osteoarthritis (OA) requires the involvement of inflammation, in which chondrocyte damage plays a significant role. Hydroxysafflor yellow A (HSYA), the main active component in the medical and edible dual‐purpose plant safflower, has previously shown anti‐inflammatory effects in various diseases. However, the specific impact of HSYA on OA remains unclear. Here, we investigate the potential role and underlying mechanism of HSYA in chondrocyte damage during the progression of OA. The viability of C28/I2 and iCell‐0092a chondrocytes was measured by CCK8 assay at different concentrations (2.5, 10, 40, and 160 μM). The gene expression of the extracellular matrix was revealed by q‐PCR 24 h after IL‐1β treatment. ROS production and levels of pro‐inflammatory cytokines in C28/I2 cells treated with HSYA were measured by immunoflurescence stating and q‐PCR. The impact of HSYA on the extracellular matrix and inflammation in IL‐1β‐induced OA were detected by western blot, q‐PCR, and immunofluorescence staining. We assessed the effect of HSYA and NF‐κB signaling pathway‐related genes by bioinformatics analysis and conducted molecular docking to assess the interaction of HSYA with a combined protein residue molecule ligand. Western blot was employed to investigate NF‐κB transcription factors in chondrocyte metabolism. HSYA was found to reduce excessive ROS production induced by IL‐1β stimuli, inhibit the expression of matrix metalloproteinase 13, interleukin 6, and tumor necrosis factor‐α, and increase the expression of Type II collagen and SRY‐box transcription factor 9 (p <.05). Mechanistically, HSYA interacted with nuclear factor κB, inhibiting the nuclear translocation and phosphorylation level of NF‐κB p65, and decreasing the phosphorylation and degradation of IκBα (p <.05). In conclusion, HSYA ameliorates inflammation and cartilage damage in OA by inhibiting the NF‐κB pathway, suggesting its potential application as a therapeutic agent for OA treatment. [ABSTRACT FROM AUTHOR]

Non‐invasive cell regulation represents a promising approach for on‐site cell modulation, but is confronted with inaccuracy or poor cell selectivity. Herein, by virtue of the interfacial‐activated concatenate DNA circuit, an activated recombination‐to‐modulation (ARM) machinery is developed to achieve accurate membrane imaging and effective cell modulation. Bioorthogonal signal transduction through the catalytic hairpin assembly circuit can continuously regenerate triggers for activating the subsequent circuit, with no activator consumption and occupation. The ARM strategy utilizes the amplified hybridization chain reaction to sensitively rearrange membrane receptors for blocking the related signaling pathways and indirectly modulating cell behaviors. Based on these two membrane receptor inputs, the controllably‐activated ARM strategy enables the identification of target cells among similar interfering cells with high accuracy and sensitivity. This machinery has demonstrated good performance in the efficient inhibition of tumor metastasis via the disruption of HGF/c‐Met‐signaling pathway. The modular‐designed ARM machinery provides a general platform for non‐invasive and specific cell modulation, suggesting a broad opportunity for advanced exploration of cellular metabolism behaviors. [ABSTRACT FROM AUTHOR]

The isothermal enzyme‐free nucleic acid amplification method plays an indispensable role in biosensing by virtue of its simple, robust, and highly efficient properties without the assistance of temperature cycling or/and enzymatic biocatalysis. Up to now, enzyme‐free nucleic acid amplification has been extensively utilized for biological assays and has achieved the highly sensitive detection of various biological targets, including DNAs, RNAs, small molecules, proteins, and even cells. In this Review, the mechanisms of entropy‐driven reaction, hybridization chain reaction, catalytic hairpin assembly and DNAzyme are concisely described and their recent application as biosensors is comprehensively summarized. Furthermore, the current problems and the developments of these DNA circuits are also discussed. [ABSTRACT FROM AUTHOR]

Synthetic catalytic DNA circuits have been recognized as a promising signal amplification toolbox for sensitive intracellular imaging, yet their selectivity and efficiency are always constrained by uncontrolled off‐site signal leakage and inefficient on‐site circuitry activation. Thus, the endogenously controllable on‐site exposure/activation of DNA circuits is highly desirable for achieving the selective imaging of live cells. Herein, an endogenously activated DNAzyme strategy was facilely integrated with a catalytic DNA circuit for guiding the selective and efficient microRNA imaging in vivo. To prevent the off‐site activation, the circuitry constitute was initially caged without sensing functions, which could be selectively liberated by DNAzyme amplifier to guarantee the high‐contrast microRNA imaging in target cells. This intelligent on‐site modulation strategy can tremendously expand these molecularly engineered circuits in biological systems. [ABSTRACT FROM AUTHOR]

Synthetic catalytic DNA circuits have been recognized as a promising signal amplification toolbox for sensitive intracellular imaging, yet their selectivity and efficiency are always constrained by uncontrolled off‐site signal leakage and inefficient on‐site circuitry activation. Thus, the endogenously controllable on‐site exposure/activation of DNA circuits is highly desirable for achieving the selective imaging of live cells. Herein, an endogenously activated DNAzyme strategy was facilely integrated with a catalytic DNA circuit for guiding the selective and efficient microRNA imaging in vivo. To prevent the off‐site activation, the circuitry constitute was initially caged without sensing functions, which could be selectively liberated by DNAzyme amplifier to guarantee the high‐contrast microRNA imaging in target cells. This intelligent on‐site modulation strategy can tremendously expand these molecularly engineered circuits in biological systems. [ABSTRACT FROM AUTHOR]

Chemiluminescence resonance energy transfer (CRET)-based assays have shown great potential in biosensing due to their negligible background autofluorescence, yet are still limited by their low sensitivity and short half-life luminescence. Herein, a multistage CRET-based DNA circuit was constructed with amplified luminescence signals for accurate miRNA detection and fixed reactive oxygen species (ROS) signals for cell imaging. The DNA circuit is designed through an ingenious programmable catalytic hairpin assembly (CHA), hybridization chain reaction (HCR), and the use of DNAzyme to realize target-triggered precise regulation of distance between the donor and acceptor for CRET-mediated excitation of photosensitizers. In detail, the analyte catalyzes the hybridization of CHA reactants, which leads to the assembly of multiple HCR-mediated DNAzyme nanowires. Subsequently, DNAzymes catalyze the oxidation of luminol by H2O2, and the adjacent photosensitizer chlorin e6 (Ce6) anchored on the DNA nanostructure is stimulated by the CRET process, resulting in the amplified long-wavelength luminescence and the generation of single oxygen signals through further energy transfer to oxygen. The biomarker miRNA can be detected with great sensitivity by integrating the recognition module into a universal platform. Furthermore, the DNA circuit enables CRET-mediated intracellular miRNA imaging, by detecting singlet oxygen signals through a ROS probe. The significant amplification effect is attributed to the robust multiple recognition of the target and the guaranteed transduction of the CRET signal through programmable engineering of DNA nanostructures. The CRET-based DNA circuit achieves amplified long-wavelength luminescence for accurate miRNA detection with low background and ROS-mediated signal fixation for cell imaging, making it a promising candidate for early diagnosis and theranostics. [ABSTRACT FROM AUTHOR]

Laser‐free photodynamic therapy (PDT) is a promising noninvasive therapeutic modality for deep‐seated tumor, yet is constrained by low efficiency due to the limited stimulation strategies. Herein, a novel miRNA‐responsive laser‐free PDT was developed through metal‐organic frameworks (MOFs)‐mediated chemiluminescence resonance energy transfer (CRET) nanoplatform. The photosensitizer chlorin e6 (Ce6)‐loaded MOFs were functionalized with hairpin nucleic acids for sensitive responsiveness of tumor biomarker miRNA through catalytic hairpin assembly (CHA), which enabled the amplified assembly of horseradish peroxidase (HRP)‐mimicking hemin/G‐quadruplex DNAzyme on MOFs. Simultaneously, the on‐MOF assembled DNAzymes efficiently catalyzed chemiluminescence reaction to stimulate adjacent Ce6 in the presence of luminol and H2O2, thus allowing the CRET‐mediated Ce6 luminescence and reactive oxygen species (ROS) generation for self‐illuminating PDT. The CRET nanoplatform achieved significant malignant cell apoptosis and tumor inhibition effects without external laser irradiation. It is envisioned that the miRNA‐amplified CRET nanoplatform might be a selective and highly efficient antitumor nanomedicine for precise theranostic. [ABSTRACT FROM AUTHOR]

DNAzymes are synthetic deoxynucleotide oligomers with catalytic properties selected through in vitro systematic evolution of ligands by exponential enrichment (SELEX) technique. RNA‐cleaving DNAzymes have attracted increasing attentions in bioanalysis and biomedical applications due to their simple synthesis and modification, stable structure, and high catalytic activity. Especially, their different modes of activity regulation enable their extensive theranostic development. This review introduces the in vitro selection of DNAzymes and some typical ones, followed by the description of various stimuli‐responsive regulation strategies on DNAzyme activity, including metal ion cofactors, small molecules, protease, light, and heat. Then the recent advances of DNAzyme‐based biosensors, therapeutic applications, cell‐cell interaction regulation, and logic operation are summarized. At last, the current challenges and possible development of DNAzyme‐based biosensors are discussed. [ABSTRACT FROM AUTHOR]

On page 5662, I. Willner and team show how K+‐ion‐stabilized G‐quadruplexes act as locks for the entrapment of substrates in mesoporous silica nanoparticles. The pores are unlocked by the Kryptofi × [2.2.2] (KP) through the removal of the K+ ions. Also, programmed duplex structures lock the anticancer drug doxorubicin in mesoporous silica nanoparticles. The pores are unlocked by the separation of the duplex through the formation of a G‐quadruplex. [ABSTRACT FROM AUTHOR]

Pb(Nd x Zr 0.52 Ti 0.48 )O 3 (PNZT) (x = 0%, 1%, 2%, 3%, 4%, 5%) thin films were prepared by sol-gel process to investigate the effects of neodymium substitution on crystalline orientation, microstructure and electric properties of lead zirconate titanate (PZT) films. X-ray diffraction (XRD) and scanning electron microscope (SEM) analysis showed that PNZT films with Nd doping concentration below 3% exhibited dense perovskite structure with (100) preferred orientation. The average grain size of PNZT films decreased as the Nd substitution increased. The maximum dielectric constant, remnant polarization and minimum coercive field were obtained in 2% Nd-doped PZT films. Fatigue resistance was also improved significantly with 2% Nd dopant. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

It is meaningful to automatically learn the valuable features from the raw vibration data and provide accurate fault diagnosis results. In this paper, an enhancement deep feature fusion method is developed for rotating machinery fault diagnosis. Firstly, a new deep auto-encoder is constructed with denoising auto-encoder (DAE) and contractive auto-encoder (CAE) for the enhancement of feature learning ability. Secondly, locality preserving projection (LPP) is adopted to fuse the deep features to further improve the quality of the learned features. Finally, the fusion deep features are fed into softmax to train the intelligent diagnosis model. The developed method is applied to the fault diagnosis of rotor and bearing. The results confirm that the proposed method is more effective and robust compared with the existing methods. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Programmable DNA materials hold great potential in biochemical and biomedical researches, yet the complicated synthesis, and the low stability and targeting efficacy in complex biological milieu limit their clinical translations. Here we show a one‐pot assembly of DNA‐protein superstructures as drug vehicles with specifically high affinity and stability for targeted therapy. This is achieved by biomimetic assembly of programmable polymer DNA wire into densely packed DNA nanosphere with an alkaline protein, protamine. Multivalent DNA nanostructures encoded with different types and densities of aptamers exhibit high affinity to targeted cells through polyvalent interaction. Our results show high cancer cell selectivity, reduced side effect, excellent therapeutic efficacy, and sensitive tumor imaging in both subcutaneous and orthotopic non‐small‐cell lung cancer murine models. This biomimetic assembly approach provides practical DNA nanomaterials for further clinical trials and may advance oligonucleotide drug delivery. [ABSTRACT FROM AUTHOR]

Programmable DNA materials hold great potential in biochemical and biomedical researches, yet the complicated synthesis, and the low stability and targeting efficacy in complex biological milieu limit their clinical translations. Here we show a one‐pot assembly of DNA‐protein superstructures as drug vehicles with specifically high affinity and stability for targeted therapy. This is achieved by biomimetic assembly of programmable polymer DNA wire into densely packed DNA nanosphere with an alkaline protein, protamine. Multivalent DNA nanostructures encoded with different types and densities of aptamers exhibit high affinity to targeted cells through polyvalent interaction. Our results show high cancer cell selectivity, reduced side effect, excellent therapeutic efficacy, and sensitive tumor imaging in both subcutaneous and orthotopic non‐small‐cell lung cancer murine models. This biomimetic assembly approach provides practical DNA nanomaterials for further clinical trials and may advance oligonucleotide drug delivery. [ABSTRACT FROM AUTHOR]

Lowly expressed analyte in complex cytoplasmic milieu necessitates the development of non‐enzymatic autocatalytic DNA circuits with high amplification and anti‐interference performance. Herein, we engineered a versatile and robust stimuli‐responsive autocatalytic hybridization assembly (AHA) circuit for high‐performance in vivo bioanalysis. Under a moderately confined condition, the initiator motivated the autonomous and cooperative cross‐activation of cascade hybridization reaction and catalytic DNA assembly for generating an exponentially amplified readout without the parasite steric hindrance and random diffusion side effects. The AHA circuit was systematically investigated by a series of experimental studies and theoretical simulations. The successively guaranteed target recognition and synergistically accelerated signal‐amplification enabled the sensitive and selective detection of analyte, and realized the robust miRNA imaging in living cells and mice. This autocatalytic DNA circuit could substantially expand the toolbox for accurate diagnosis and programmable therapeutics. [ABSTRACT FROM AUTHOR]

Lowly expressed analyte in complex cytoplasmic milieu necessitates the development of non‐enzymatic autocatalytic DNA circuits with high amplification and anti‐interference performance. Herein, we engineered a versatile and robust stimuli‐responsive autocatalytic hybridization assembly (AHA) circuit for high‐performance in vivo bioanalysis. Under a moderately confined condition, the initiator motivated the autonomous and cooperative cross‐activation of cascade hybridization reaction and catalytic DNA assembly for generating an exponentially amplified readout without the parasite steric hindrance and random diffusion side effects. The AHA circuit was systematically investigated by a series of experimental studies and theoretical simulations. The successively guaranteed target recognition and synergistically accelerated signal‐amplification enabled the sensitive and selective detection of analyte, and realized the robust miRNA imaging in living cells and mice. This autocatalytic DNA circuit could substantially expand the toolbox for accurate diagnosis and programmable therapeutics. [ABSTRACT FROM AUTHOR]

The direct visualization of vaccine fate is important to investigate its immunoactivation process to elucidate the detailed molecular reaction process at single‐molecular level. Yet, visualization of the spatiotemporal trafficking of vaccines remains poorly explored. Here, we show that quantum dot (QD) nanomaterials allow for monitoring vaccine dynamics and for amplified immune response. Synthetic QDs enable efficient conjugation of antigen and adjuvants to target tissues and cells, and non‐invasive imaging the trafficking dynamics to lymph nodes and cellular compartments. The nanoparticle vaccine elicits potent immune responses and anti‐tumor efficacy alone or in combination with programmed cell death protein 1 blockade. The synthetic QDs showed high fluorescence quantum yield and superior photostability, and the reliable and long‐term spatiotemporal tracking of vaccine dynamics was realized for the first time by using the synthetic QDs, providing a powerful strategy for studying immune response and evaluating vaccine efficacy. [ABSTRACT FROM AUTHOR]

The direct visualization of vaccine fate is important to investigate its immunoactivation process to elucidate the detailed molecular reaction process at single‐molecular level. Yet, visualization of the spatiotemporal trafficking of vaccines remains poorly explored. Here, we show that quantum dot (QD) nanomaterials allow for monitoring vaccine dynamics and for amplified immune response. Synthetic QDs enable efficient conjugation of antigen and adjuvants to target tissues and cells, and non‐invasive imaging the trafficking dynamics to lymph nodes and cellular compartments. The nanoparticle vaccine elicits potent immune responses and anti‐tumor efficacy alone or in combination with programmed cell death protein 1 blockade. The synthetic QDs showed high fluorescence quantum yield and superior photostability, and the reliable and long‐term spatiotemporal tracking of vaccine dynamics was realized for the first time by using the synthetic QDs, providing a powerful strategy for studying immune response and evaluating vaccine efficacy. [ABSTRACT FROM AUTHOR]