Difference in mortality risk predicted by leukocyte and lymphocyte levels in COVID-19 patients infected with the Wild-type, Delta, and Omicron strains.

This study aimed to investigate the changing trends, level differences, and prognostic performance of the leukocyte and lymphocyte levels of patients infected with the Wild strains, Delta strains and Omicron strains to provide a reference for prognostic assessment. In the current study, we conducted a retrospective cross-sectional study to evaluate the changing trends, level differences, and prognostic performance of leukocyte and lymphocyte of different strains at admission and discharge may already exist in patients with coronavirus disease-2019 (COVID-19) infected with the Wild type, Delta, and Omicron strains. A retrospective cross-sectional study was conducted. We recruited and screened the 243 cases infected with the Wild-type strains in Wuhan, the 629 cases infected with the Delta and 116 cases infected strains with the Omicron strains in Xi'an. The leukocyte and lymphocyte levels were compared the cohort of Wild-type infection with the cohort of Delta and the Omicron. The changes in the levels of leukocytes and lymphocytes exhibit a completely opposite trend in patients with COVID-19 infected with the different strains. The lymphocyte level at admission and discharge in patients with COVID-19 infected with Omicron strains (area under curve [AUC] receiver operating characteristic curve [ROC] 72.8-90.2%, 82.8-97.2%) presented better performance compared patients with COVID-19 infected with Wild type strains (AUC ROC 60.9-80.7%, 82.3-97.2%) and Delta strains (AUC ROC 56.1-84.7%, 40.3-93.3%). Kaplan-Meier curves showed that the leukocyte levels above newly established cutoff values and the lymphocyte levels below newly established cutoff values had a significantly higher risk of in-hospital mortality in COVID-19 patients with Wild-type and Omicron strains (P < .01). The levels of leukocyte and lymphocyte at admission and discharge in patients with COVID-19 infected with the Wild type, Delta, and Omicron strains may be differences among strains, which indicates different death risks. Our research may help clinicians identify patients with a poor prognosis for severe acute respiratory syndrome coronavirus 2 infection.

Polymerized carbon dots with high electrochemiluminescence efficiency and long wavelength ECL emission for ultrasensitive detection of MicroRNA-222.

Herein, a new electrochemiluminescence (ECL) biosensor was constructed with highly efficient polymerized carbon dots (PCDs) as ECL emitter and the improved localized catalytic hairpin assembly (L-CHA) as signal amplifier for ultrasensitive detection of microRNA-222 (miRNA-222). Impressively, compared to the traditional carbon dots with inefficient blue region ECL emission, PCDs with N, O co-dope and large conjugated π-system showed high electrical conductivity, narrow band gap and strong radiative transition, which could exhibit high ECL efficiency to improve the sensitivity of detection and long wavelength ECL emission to achieve deep tissue penetration for reducing biological damage. Furthermore, the trace target miRNA-222 could be efficiently converted into large amounts of output DNA labelled with the quencher dopamine (S-DA) through the L-CHA reaction to significantly enhance the target amplification efficiency for further improving the sensitivity of detection. Thus, the ECL biosensor could achieve the ultrasensitive detection of miRNA-222 from 100 aM to 100 pM with the detection limit of 76 aM. Therefore, this work proposed a novel CDs with high ECL efficiency and long wavelength ECL emission, which not only was used to build an ultrasensitive biosensor for biomolecules detection in clinical diagnosis, but also served as a potential emitter for ECL bioimaging.

Phoenixin 20 ameliorates pulmonary arterial hypertension via inhibiting inflammation and oxidative stress.

Pulmonary arterial hypertension (PAH) is a severe pathophysiological syndrome resulting in heart failure, which is found to be induced by pulmonary vascular remodeling mediated by oxidative stress (OS) and inflammation. Phoenixin-20 (PNX-20) is a reproductive peptide first discovered in mice with potential suppressive properties against OS and inflammatory response. Our study will explore the possible therapeutic functions of PHN-20 against PAH for future clinical application. Rats were treated with normal saline, PHN-20 (100 ng/g body weight daily), hypoxia, hypoxia+PHN-20 (100 ng/g body weight daily), respectively. A signally elevated RVSP, mPAP, RV/LV + S, and W%, increased secretion of cytokines, enhanced malondialdehyde (MDA) level, repressed superoxide dismutase (SOD) activity, and activated NLRP3 signaling were observed in hypoxia-stimulated rats, which were notably reversed by PHN-20 administration. Pulmonary microvascular endothelial cells (PMECs) were treated with hypoxia with or without PHN-20 (10 and 20 nM). Marked elevation of inflammatory cytokine secretion, increased MDA level, repressed SOD activity, and activated NLRP3 signaling were observed in hypoxia-stimulated PMECs, accompanied by a downregulation of SIRT1. Furthermore, the repressive effect of PHN-20 on the domains-containing protein 3 (NLRP3) pathway in hypoxia-stimulated PMECs was abrogated by sirtuin1 (SIRT1) knockdown. Collectively, PHN-20 alleviated PAH via inhibiting OS and inflammation by mediating the transcriptional function of SIRT1.

Renewable Electrochemiluminescence Biosensor Based on Eu-MOGs as a Highly Efficient Emitter and a DNAzyme-Mediated Dual-drive DNA Walker as a Signal Amplifier for Ultrasensitive Detection of miRNA-222.

Herein, novel europium metal-organic gels (Eu-MOGs) with excellent cathode electrochemiluminescence (ECL) emission are first used to construct biosensors for the ultrasensitive detection of miRNA-222. Impressively, N and O elements of organic ligand 2,2':6,2″-terpyridine 4,4',4″-tricarboxylic acid (H3-tctpy) can perfectly coordinate with Eu3+ to form Eu-MOGs, which not only reduce nonradiative transition caused by the intramolecular free rotation of phenyl rings in other MOGs to enhance the ECL signal with extraordinary ECL efficiency as high as 37.2% (vs the [Ru(bpy)3]2+/S2O82- ECL system) but also reinforce ligand-to-metal charge transfer (LMCT) by the strong affinity between Eu3+ and N and O elements to greatly improve the stability of ECL signals. Besides, an improved nucleic acid cascade amplification reaction is developed to greatly raise the conversion efficiency from target miRNA-222 to a DNAzyme-mediated dual-drive DNA walker as output DNA, which can simultaneously shear the specific recognition sites from two directions. In that way, the proposed biosensor can further enhance the detection sensitivity of miRNA-222 with a linear range of 10 aM-1 nM and a detection limit (LOD) of 8.5 aM, which can also achieve an accurate response in cancer cell lysates of MHCC-97L and HeLa. Additionally, the biosensor can be self-regenerated by the folding/unfolding of related triplets with pH changes to simplify experimental operations and reduce the cost. Hence, this work proposed novel MOGs with stable and intense ECL signals for the construction of a renewable ECL biosensor, supplying a reliable detection method in biomarker analysis and disease diagnosis.

Dynamic surface reconstruction of individual gold nanoclusters by using a co-reactant enables color-tunable electrochemiluminescence.

Here we report for the first time the phenomenon of continuously color-tunable electrochemiluminescence (ECL) from individual gold nanoclusters (Au NCs) confined in a porous hydrogel matrix by adjusting the concentration of the co-reactant. Specifically, the hydrogel-confined Au NCs exhibit strong dual-color ECL in an aqueous solution with triethylamine (TEA) as a co-reactant, with a record-breaking quantum yield of 95%. Unlike previously reported Au NCs, the ECL origin of the hydrogel-confined Au NCs is related to both the Au(0) kernel and the Au(i)-S surface. Surprisingly, the surface-related ECL of Au NCs exhibits a wide color-tunable range of 625-829 nm, but the core-related ECL remains constant at 489 nm. Theoretical and experimental studies demonstrate that the color-tunable ECL is caused by the dynamic surface reconstruction of Au NCs and TEA radicals. This work opens up new avenues for dynamically manipulating the ECL spectra of core-shell emitters in biosensing and imaging research.

A simple and reliable interenzyme distance regulation strategy based on a DNA quadrangular prism scaffold for ultrasensitive ochratoxin A detection.

Developing sensitive and accurate Ochratoxin A (OTA) detection methods is essential for food safety. Herein, a simple and reliable strategy for regulating interenzyme distance based on a rigid DNA quadrangular prism as a scaffold was proposed to establish a new electrochemical biosensor for ultrasensitive detection of OTA. The interenzyme distances were precisely adjusted by changing the sequences of the hybridized portions of hairpins SH1 and SH2 to the DNA quadrangular prism, avoiding the complexity and instability of the previous DNA scaffold-based enzyme spacing adjustment strategies. The electrochemical biosensor constructed at the optimal interenzyme distance (10.4 nm) achieved sensitive detection of OTA in a dynamic concentration range from 10 fg/mL to 250 ng/mL with a detection limit of 3.1 fg/mL. In addition, the biosensor was applied to quantify OTA in real samples, exhibiting great application potential in food safety.

Antibody-Protein-Aptamer Electrochemical Biosensor based on Highly Efficient Proximity-Induced DNA Hybridization on Tetrahedral DNA Nanostructure for Sensitive Detection of Insulin-like Growth Factor-1.

Herein, an antibody-protein-aptamer electrochemical biosensor was designed by highly efficient proximity-induced DNA hybridization on a tetrahedral DNA nanostructure (TDN) for ultrasensitive detection of human insulin-like growth factor-1 (IGF-1). Impressively, the IGF-1 antibody immobilized on the top vertex of the TDN could effectively capture the target protein with less steric effect, and the ferrocene-labeled signal probe (SP) bound on the bottom vertex of the TDN was close to the electrode surface for generating a strong initial signal. In the presence of target protein IGF-1 and an aptamer strand, an antibody-protein-aptamer sandwich could be formed on the top vertex of TDN, which would trigger proximity-induced DNA hybridization to release the SP on the bottom vertex of TDN; therefore, the signal response would decrease dramatically, enhancing the sensitivity of the biosensor. As a result, the linear range of the proposed biosensor for target IGF-1 was 1 fM to 1 nM with the limit of detection down to 0.47 fM, which was much lower than that of the traditional TDN designs on electrochemical biosensors. Surprisingly, the use of this approach offered an innovative approach for the sensitive detection of biomarkers and illness diagnosis.

Long-Wavelength Illumination-Induced Photocurrent Enhancement of a ZnPc Photocathodic Material for Bioanalytical Applications.

Herein, a novel photocathodic nanocomposite poly{4,8-bis[5-(2-ethylhexyl)-thiophen-2-yl] benzo[1,2-b:4,5-b']dithiophene-2,6-diyl-alt-3-fluoro-2-[(2-ethylhexyl)-carbonyl]thieno[3,4-b]thiophene-4,6-diyl}/phthalocyanine zinc (PTB7-Th/ZnPc) with high photoelectric conversion efficiency under long-wavelength illumination was prepared to construct an ultrasensitive biosensor for the detection of microRNA-21 (miRNA-21), accompanied by a prominent anti-interference capability toward reductive substances. Impressively, the new heterojunction PTB7-Th/ZnPc nanocomposite could not only generate a strong cathodic photocurrent to improve the detection sensitivity under long-wavelength illumination (660 nm) but also effectively avoid the high damage of biological activity caused by short-wavelength light stimulation. Accordingly, by coupling with rolling circle amplification (RCA)-triggered DNA amplification to form functional biquencher nanospheres, a PEC biosensor was fabricated to realize the ultrasensitive analysis of miRNA-21 in the concentration range of 0.1 fM to 10 nM with a detection limit as low as 32 aM. This strategy provided a novel long-wavelength illumination-induced photocurrent enhancement photoactive material for a sensitive and low-damage anti-interference bioassay and early clinical disease diagnosis.

Selenium and nitrogen co-doped carbon dots with highly efficient electrochemiluminescence for ultrasensitive detection of microRNA.

In this work, selenium and nitrogen co-doped carbon dots (SeN-CDs) possessing highly efficient electrochemiluminescence (ECL) and excellent biocompatibility were synthesized as a new emitter with S2O82- as a coreactant for constructing a biosensor to detect microRNA-221 (miRNA-221) sensitively. Notably, the SeN-CDs exhibited superior ECL performance compared with the N-doped CDs, in which selenium with excellent redox activity served as a coreaction accelerator for facilitating the electroreduction of S2O82- to significantly improve ECL efficiency. Furthermore, target-induced T7 exonuclease (T7 Exo)-assisted double cycle amplification strategy could convert traces of target miRNA-221 into large amounts of output DNA to capture three-dimensional (3D) nanostructures (DTN-Au NPs-DOX-Fc) loaded with large amounts of ECL signal quencher. The constructed biosensor could realize ultrasensitive detection of miRNA-221 and has a low detection limit reaching 2.3 aM, with a successful application to detect miRNA-221 in lysate of Hela and MHCC97-L cancer cell. This work explored a novel method to strengthen the ECL performance of CDs to construct an ECL biosensing platform with sensitive detecting of biomarkers and disease diagnosis.

Orderly Aggregated Catalytic Hairpin Assembly for Synchronous Ultrasensitive Detecting and High-Efficiency Co-Localization Imaging of Dual-miRNAs in Living Cells.

In this work, the orderly aggregated catalytic hairpin assembly (OA-CHA) was developed for synchronous ultrasensitive detection and high-efficiency colocalization imaging of dual-miRNAs by a carefully designed tetrahedral conjugated ladder DNA structure (TCLDS). Exactly, two diverse hairpin probes were fixed on tetrahedron conjugated DNA nanowires to form the TCLDS without fluorescence response, which triggered OA-CHA in the aid of output DNA 1 and output DNA 2 produced by targets miRNA-217 and miRNA-196a cycle to generate TCLDS with remarkable fluorescence response. Impressively, compared with the traditional CHA strategy, OA-CHA avoided the fluorescence group and quenching group from approaching again because of the spatial confinement effect to significantly enhance the fluorescence signal, resulting in the simultaneous ultrasensitive detection of dual-miRNAs with detection limits of 21 and 32 fM for miRNA-217 and miRNA-196a, respectively. Meanwhile, the TCLDS with lower diffusivity could achieve accurate localization imaging for reflecting the spatial distribution of dual-miRNAs in living cells. The strategy based on OA-CHA provided a flexible and programmable nucleic amplification method for the synchronous ultrasensitive detection and precise imaging of multiple biomarkers and had potential in disease diagnostics..

Gold Nanobipyramid Hotspot Aggregation-Induced Surface-Enhanced Raman Scattering for the Ultrasensitive Detection of miRNA.

Herein, a surface-enhanced Raman scattering (SERS) biosensor was constructed by gold nanobipyramid (Au NBP) hotspot aggregation-induced SERS (HAI-SERS) for the ultrasensitive detection of microRNA-221 (miRNA-221). Impressively, compared with single Au NBP, the multiple Au NBPs assembled by tetrahedral DNA nanostructures (TDNs) could increase hotspot aggregation to significantly enhance the SERS signal of Raman molecule methylene blue (MB). Meanwhile, in the aid of Exo-III assisted target cycle amplification and TDNs-induced catalytic hairpin assembly (CHA) amplification, the biosensor could achieve the sensitive detection of miRNA-221 with a linear range of 1 fM-10 nM, and the limit of detection (LOD) was 0.59 fM, which could be used for practical application in MHCC-97L and MCF-7 cell lysates. This work provided a method for hotspot aggregation to enhance SERS for the detection of biomarkers and disease diagnosis.

Copper nanoclusters electrochemiluminescence with tunable near-infrared emission wavelength for ultrasensitive detection of matrix metalloproteinase-2.

Herein, the methionine (Met)/N-acetyl-L-cysteine (NAC) templated copper nanoclusters (Met/NAC-Cu NCs) with tunable near-infrared region (NIR) electrochemiluminescence (ECL) emission wavelength was firstly synthesized as emitter for the ultrasensitive detection of matrix metalloproteinase-2 (MMP-2). Significantly, the NAC played the role of template and reductant of cupric to acquire Cu NCs, and the surface defect regulator Met was used to connect NAC through -S-S- bond, which could heighten the surface defect of Cu NCs to continuously regulate the maximum ECL emission by successively controlling the molar ratio of Met and NAC, leading to the ECL emission wavelength of Cu NCs ranged from 680 nm to 750 nm. In addition, a rapid target triggered catalyst hairpin assembly (CHA) recycling amplification strategy was constructed through orderly and equidistantly arranging hairpin to increase its local concentration, resulting in greatly accelerated signal amplification efficiency and reaction rate. As a proof of concept, based on Met/NAC-Cu NCs as NIR ECL emitter and effective signal amplification tactic, a super-sensitive ECL biosensor was fabricated to detect target MMP-2 with the detection limit (LOD) as low as 1.65 fg/mL and successfully utilized for detecting of MMP-2 that from Hela and MCF-7 cancer cells. This research provided a wonderful avenue for regulating the optical performance of metal nanoclusters-based ECL emitters, and the developed neoteric NIR ECL emitter with the merits of less photochemical damage and deeper tissue penetration exhibited great potential in ultrasensitive biosensing and high-definition ECL imaging.

pH-Stimulated Self-Locked DNA Nanostructure for the Effective Discrimination of Cancer Cells and Simultaneous Detection and Imaging of Endogenous Dual-MicroRNAs.

In this study, a pH-stimulated self-locked DNA nanostructure (SLDN) was developed to efficiently distinguish cancer cells from other cells for the simultaneous detection and imaging of endogenous dual-microRNAs (miRNAs). Impressively, the SLDN was specifically unlocked in the acidic environment of cancer cells to form unlocked-SLDN to disengage the i-motif sequence with a labeled fluorophore for the recovery of a fluorescence signal, resulting in the differentiation of cancer cells from normal cells. Meanwhile, unlocked-SLDN could combine and recognize the targets miRNA-21 and miRNA-155 simultaneously to trigger the hybridization chain reaction (HCR) amplification for sensitive dual-miRNA detection, with detection limits of 1.46 pM for miRNA-21 and 0.72 pM for miRNA-155. Significantly, compared with the current miRNA imaging strategy based on the traditional DNA nanostructure, the strategy proposed here remarkably eliminates the interference of normal cells to achieve high-resolution colocation imaging of miRNAs in tumor cells with an ultralow background signal. This work provided a specific differentiation method for tumor cells to materialize sensitive biomarker detection and distinguishable high-definition live-cell imaging for precise cancer diagnosis and multifactor research of tumor progression.

Near-Infrared-Driven Nanorocket for Rapid and Ultrasensitive Detection of MicroRNA.

Herein, by introducing gold nanostars (AuNSs) as fuel core, a near-infrared-driven nanorocket (NIDNR) with pretty fast walking was exploited for ultrasensitive miRNA detection. Compared with traditional nanomaterials-comprised nanomachines (NMs), the NIDNR possesses much better kinetic and thermodynamic performance owing to the extra photothermal driving force from localized surface plasmon (LSP). Impressively, the whole reaction time of NIDNR down to 15 min was realized, which is almost more than 8 times beyond those of conventional DNA-based NMs. This way, the inherent obstacle of traditional NMs, including long reaction time and low efficiency, could be easily addressed. As a proof of concept, the NIDNR was successfully applied to develop an electrochemical biosensing platform for rapid and sensitive detection of miRNA with an LOD down to 2.95 aM and achieved the real-time assay of real biological samples from human hepatocellular carcinoma cells (MHCC97L) and HeLa, thus providing an innovative insight to design more versatile DNA nanomachines for ultimate application in biosensing platform construction and clinical sample detection.

Efficient Three-Dimensional DNA Nanomachine Guided by a Robust Tetrahedral DNA Nanoarray Structure for the Rapid and Ultrasensitive Electrochemical Detection of Matrix Metalloproteinase 2.

Herein, a giant-sized DNA nanoarray was subtly assembled by two kinds of independent tetrahedral DNA structures as the DNA track for a multi-armed three-dimensional (3D) DNA nanomachine to perform signal transduction and amplification efficiently, which was developed as an electrochemical biosensor for the rapid and ultrasensitive detection of matrix metalloproteinase 2 (MMP-2). Impressively, in contrast to conventional DNA walkers with inefficiency, which walked on random DNA tracks composed of a two-dimensional (2D) probe or a one-dimensional (1D) single-stranded (ss)DNA probe, the multi-armed 3D DNA nanomachine from exonuclease III (Exo III) enzyme-assisted target recycling amplification would be endowed with faster reaction speed and better walking efficiency because of the excellent rigidity and orderliness of the tetrahedral DNA nanoarray structure. Once the hairpin H3-label with the signal substance ferrocene (Fc) was added to the modified electrode surface, the multi-armed 3D DNA nanomachine would be driven to move along the well-designed nanoarray tracks by toehold-mediated DNA strand displacement, resulting in most of the ferrocene (Fc) binding to the electrode surface and a remarkable increase in electrochemical signals within 60 min. As a proof of concept, the prepared biosensor attained a low detection limit of 11.4 fg/mL for the sensitive detection of the target MMP-2 and was applied in Hela and MCF-7 cancer cell lysates. As a result, this strategy provided a high-performance sensing platform for protein detection in tumor diagnosis.

Ultrasensitive Photocathodic Biosensor Based on the Cu2O/PTB7-Th/PDA+ Composite with Enhanced Photoelectrochemical Performance for the Detection of MicroRNA-375-3p.

Herein, an ultrasensitive photocathodic biosensor was fabricated based on Cu2O/PTB7-Th/PDA+ photoactive materials with high photocarrier separation efficiency for the detection of microRNA-375-3p. Impressively, the photocathodic signal of the Cu2O material was significantly enhanced by using PTB7-Th as an energy level-matching photoactive material to enhance the bulk charge separation and N,N-bis (2-(trimethylammoniumiodide) propylene) perylene-3,4,9,10-tetracarboxydiimide (PDA+) as an interfacial charge transfer mediator to efficiently suppress charge recombination at the photoelectrode/electrolyte interface. Compared with the pristine Cu2O as a photocathode, the obtained Cu2O/PTB7-Th/PDA+ exhibited a 17 times higher photocathodic signal. As a proof of concept, a PEC biosensor was fabricated by using Cu2O/PTB7-Th/PDA+ as a photoactive material and a target-triggered 3D DNA walker integrated with the dumbbell hybridization chain reaction (DHCR) as a signal amplifier to achieve the sensitive detection of microRNA-375-3p with a detection limit of 0.3 fM. This work provided a method to increase the photocurrent signal and the sensitivity of PEC-sensing platforms for the detection of biomarkers and disease diagnosis.

Self-accelerated DNA walker mediated electrochemical biosensor for rapid and ultrasensitive detection of microRNA.

Herein, we developed a novel three-dimensional (3D) self-accelerated DNA walker (SADW) which progressively expedite walking rate by unlocking the more walking arm continuously in walker process to construct electrochemical biosensor for ultrasensitive detection of microRNA. Particularly, we skillfully introduced a target analogue sequence in the double-loop hairpin, which could be released in the walking process of SADW, then rapidly activating more silenced walking strands to achieve the continuous self-acceleration, resulting in the expedited reaction rate. Surprisingly, the average reaction rate of SADW was quite higher than that of traditional 3D self-circulating DNA walkers (DW) under pretty low target miRNA concentration, which is ascribed to the outstanding acceleration process of the SADW, readily conquering the major predicaments of DW in detecting target with traces concentration: slow reaction rate and low sensitivity. This way, the elaborated SADW is favorably applied in the ultrasensitive and rapid detection of miRNA-21 in tumor cancer cell lysates with a detection limit down to 5.81 aM which was far from lower than the detection limit of DW. This approach develops the novel generation of widespread strategy for the applications in clinic diagnose, biosensing assay, and DNA nanobiotechnology.

Dual-layer 3D DNA nanostructure: The next generation of ultrafast DNA nanomachine for microRNA sensing and intracellular imaging.

The working efficiency of traditional 3D DNA nanomachines is extremely restricted due to the complex DNA components modified on nanoparticles in the same spatial height. Herein, an ultrafast dual-layer 3D DNA nanomachine (UDDNM) based on catalytic hairpin assembly (CHA) was developed by assembling two different lengths of hairpin DNA on the surface of gold nanoparticles, the long hairpin 1 (H1), to capture the trigger, and the short hairpin 2 (H2), as the signal probe, to recycle the trigger. Compared to the traditional single-layer 3D DNA nanomachine, the dual-layer 3D DNA nanostructure greatly enhances the effective collision between trigger and targeted DNA probe, H1, since the H1 located in outer layer would react with the trigger, inhibiting the invalid collision between the trigger and residual DNA component, H2, and remarkably decreasing the steric hindrance associated with the nucleic acids layer around the nanoparticles. Especially, when the distance of two layers was fixed at 3 nm, the corresponding UDDNM could accomplish the overall reaction only in 3 min with a dramatically high initial rate of up to 5.93 × 10-7 M s-1, which was at least 5-fold beyond that of the typical single-layer 3D DNA nanomachines. As a proof of concept, the described UDDNM was successfully applied in ultrasensitive fluorescence detection and sensitive intracellular imaging of miRNA-21. Consequently, our strategy, based on the creation of dual-layer 3D DNA nanostructure, may create a new approach to designing the next generation of DNA nanomachine and has enormous potential for applications in bio-analysis, logic gate operations, and clinical diagnoses.

AgAuS Quantum Dots as a Highly Efficient Near-Infrared Electrochemiluminescence Emitter for the Ultrasensitive Detection of MicroRNA.

Herein, the novel alloyed silver gold sulfur quantum dots (AgAuS QDs) with highly efficient near-infrared (NIR) electrochemiluminescence (ECL) emission at 707 nm were successfully prepared to construct a biosensing platform for ultrasensitive detection of microRNA-222 (miRNA-222). Interestingly, AgAuS QDs revealed excellent ECL efficiency (34.91%) compared to that of Ag2S QDs (10.30%), versus the standard [Ru(bpy)3]2+/S2O82- system, which benefited from the advantages of abundant surface defects and narrow bandgaps by Au incorporation. Additionally, an improved localized catalytic hairpin self-assembly (L-CHA) system was developed to display an increased reaction speed by improving the local concentration of DNA strands, which addressed the obstacles of time-consuming traditional CHA systems. As a proof of concept, based on AgAuS QDs as an ECL emitter and improved localized CHA systems as a signal amplification strategy, a "signal on-off" ECL biosensor was developed to exhibit a superior reaction rate and excellent sensitivity with a detection limit of 10.5 aM for the target miRNA-222, which was further employed for the analysis of miRNA-222 from cancer cell (MHCC-97L) lysate. This work advances the exploration of highly efficient NIR ECL emitters to construct an ultrasensitive biosensor for the detection of biomolecules in disease diagnosis and NIR biological imaging.

An electrochemiluminescence immunosensor based on multipath signal catalytic amplification integrated in a Cu2+-PEI-Pt/AuNC nanocomposite.

Here, the nanocomposite Cu2+-PEI-Pt/AuNCs with multipath signal catalytic amplification for a peroxydisulfate-dissolved oxygen electrochemiluminescence (ECL) system was prepared to fabricate a sensitive ECL immunosensor. Using polyethyleneimine (PEI), a linear polymer, as the reductant and template, Pt/Au nanochains (Pt/AuNCs) were prepared. Abundant PEI would adsorb on the surface of Pt/AuNCs via Pt-N or Au-N bonds, and further coordinate with Cu2+ to give the final nanocomposite Cu2+-PEI-Pt/AuNCs which possessed multipath signal catalytic amplification for the ECL of the peroxydisulfate-dissolved oxygen system in the presence of H2O2. First, PEI, as an effective co-reactant, could directly enhance the ECL intensity. Second, Pt/AuNCs could not only act as a mimicking enzyme to promote the decomposition of H2O2 to produce more oxygen in situ, but also act as an effective co-reaction accelerator to facilitate the generation of more co-reactive intermediate groups from peroxydisulfate, resulting in an obviously enhanced ECL signal. Then, Cu2+ could also accelerate the decomposition of H2O2 to produce more oxygen in situ, leading to a further improvement of the ECL response. Using Cu2+-PEI-Pt/AuNCs as a loading platform, a sandwiched ECL immunosensor was fabricated. As a result, the obtained ECL immunosensor possessed an ultra-sensitive detection performance for α-1-fetoprotein, providing effective information on the diagnosis and treatment of related diseases.