Enhanced amygdala-cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation.

Sleep loss robustly disrupts mood and emotion regulation in healthy individuals but can have a transient antidepressant effect in a subset of patients with depression. The neural mechanisms underlying this paradoxical effect remain unclear. Previous studies suggest that the amygdala and dorsal nexus (DN) play key roles in depressive mood regulation. Here, we used functional MRI to examine associations between amygdala- and DN-related resting-state connectivity alterations and mood changes after one night of total sleep deprivation (TSD) in both healthy adults and patients with major depressive disorder using strictly controlled in-laboratory studies. Behavioral data showed that TSD increased negative mood in healthy participants but reduced depressive symptoms in 43% of patients. Imaging data showed that TSD enhanced both amygdala- and DN-related connectivity in healthy participants. Moreover, enhanced amygdala connectivity to the anterior cingulate cortex (ACC) after TSD associated with better mood in healthy participants and antidepressant effects in depressed patients. These findings support the key role of the amygdala-cingulate circuit in mood regulation in both healthy and depressed populations and suggest that rapid antidepressant treatment may target the enhancement of amygdala-ACC connectivity.

Pseudorabies virus upregulates low-density lipoprotein receptors to facilitate viral entry.

Pseudorabies virus (PRV) is the causative agent of Aujeszky's disease in pigs. The low-density lipoprotein receptor (LDLR) is a transcriptional target of the sterol-regulatory element-binding proteins (SREBPs) and participates in the uptake of LDL-derived cholesterol. However, the involvement of LDLR in PRV infection has not been well characterized. We observed an increased expression level of LDLR mRNA in PRV-infected 3D4/21, PK-15, HeLa, RAW264.7, and L929 cells. The LDLR protein level was also upregulated by PRV infection in PK-15 cells and in murine lung and brain. The treatment of cells with the SREBP inhibitor, fatostatin, or with SREBP2-specific small interfering RNA prevented the PRV-induced upregulation of LDLR expression as well as viral protein expression and progeny virus production. This suggested that PRV activated SREBPs to induce LDLR expression. Furthermore, interference in LDLR expression affected PRV proliferation, while LDLR overexpression promoted it. This indicated that LDLR was involved in PRV infection. The study also demonstrated that LDLR participated in PRV invasions. The overexpression of LDLR or inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), which binds to LDLR and targets it for lysosomal degradation, significantly enhanced PRV attachment and entry. Mechanistically, LDLR interacted with PRV on the plasma membrane, and pretreatment of cells with LDLR antibodies was able to neutralize viral entry. An in vivo study indicated that the treatment of mice with the PCSK9 inhibitor SBC-115076 promoted PRV proliferation. The data from the study indicate that PRV hijacks LDLR for viral entry through the activation of SREBPs.IMPORTANCEPseudorabies virus (PRV) is a herpesvirus that primarily manifests as fever, pruritus, and encephalomyelitis in various domestic and wild animals. Owing to its lifelong latent infection characteristics, PRV outbreaks have led to significant financial setbacks in the global pig industry. There is evidence that PRV variant strains can infect humans, thereby crossing the species barrier. Therefore, gaining deeper insights into PRV pathogenesis and developing updated strategies to contain its spread are critical. This study posits that the low-density lipoprotein receptor (LDLR) could be a co-receptor for PRV infection. Hence, strategies targeting LDLR may provide a promising avenue for the development of effective PRV vaccines and therapeutic interventions.

Test-retest reliability and time-of-day variations of perfusion imaging at rest and during a vigilance task.

Arterial spin-labeled perfusion and blood oxygenation level-dependent functional MRI are indispensable tools for noninvasive human brain imaging in clinical and cognitive neuroscience, yet concerns persist regarding the reliability and reproducibility of functional MRI findings. The circadian rhythm is known to play a significant role in physiological and psychological responses, leading to variability in brain function at different times of the day. Despite this, test-retest reliability of brain function across different times of the day remains poorly understood. This study examined the test-retest reliability of six repeated cerebral blood flow measurements using arterial spin-labeled perfusion imaging both at resting-state and during the psychomotor vigilance test, as well as task-induced cerebral blood flow changes in a cohort of 38 healthy participants over a full day. The results demonstrated excellent test-retest reliability for absolute cerebral blood flow measurements at rest and during the psychomotor vigilance test throughout the day. However, task-induced cerebral blood flow changes exhibited poor reliability across various brain regions and networks. Furthermore, reliability declined over longer time intervals within the day, particularly during nighttime scans compared to daytime scans. These findings highlight the superior reliability of absolute cerebral blood flow compared to task-induced cerebral blood flow changes and emphasize the importance of controlling time-of-day effects to enhance the reliability and reproducibility of future brain imaging studies.

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.

Single-Atom Iron Doped Carbon Dots with Highly Efficient Electrochemiluminescence for Ultrasensitive Detection of MicroRNAs.

Herein, single-atom iron doped carbon dots (SA Fe-CDs) were successfully prepared as novel electrochemiluminescence (ECL) emitters with high ECL efficiency, and a biosensor was constructed to ultrasensitively detect microRNA-222 (miRNA-222). Importantly, compared with the conventional without single-atom doped CDs with low ECL efficiency, SA Fe-CDs exhibited strong ECL efficiency, in which single-atom iron as an advanced coreactant accelerator could significantly enhance the generation of reactive oxygen species (ROS) from the coreactant S2O82- for improving the ECL efficiency. Moreover, a neoteric amplification strategy combining the improved strand displacement amplification with Nt.BbvCI enzyme-induced target amplification (ISDA-EITA) could produce 4 output DNAs in every cycle, which greatly improved the amplification efficiency. Thus, a useful ECL biosensor was built with a detection limit of 16.60 aM in the range of 100 aM to 1 nM for detecting traces of miRNA-222. In addition, miRNA-222 in cancer cell lysate (MHCC-97L) was successfully detected by using the ECL biosensor. Therefore, this strategy provides highly efficient single-atom doped ECL emitters for the construction of sensitive ECL biosensing platforms in the biological field and clinical diagnosis.

Dual-Ligand Europium-Organic Gels as a Highly Efficient Anodic Annihilation Electrochemiluminescence Emitter for Ultrasensitive Detection of MicroRNA.

In this study, a novel europium dual-ligand metal-organic gel (Eu-D-MOGs) with high-efficient anodic annihilation electrochemiluminescence (ECL) was synthesized as an ECL emitter to construct a biosensor for ultrasensitive detection of microRNA-221 (miR-221). Impressively, compared to the ECL signal of europium single-ligand metal-organic gels (Eu-S-MOGs), the ECL signal of Eu-D-MOGs was significantly improved since the two organic ligands could jointly replace the H2O and coordinate with Eu3+, which could remarkably reduce the nonradiative vibrational energy transfer caused by the coordination between H2O and Eu3+ with a high coordination demand. In addition, Eu-D-MOGs could be electrochemically oxidized to Eu-D-MOGs•+ at 1.45 V and reduced to Eu-D-MOGs•- at 0.65 V to achieve effective annihilation of ECL, which overcame the side reaction brought by the remaining emitters at negative potential. This benefited from the annihilation ECL performance of the central ion Eu3+ caused by its redox in the electrochemical process. Furthermore, the annihilation ECL signal of Eu3+ could be improved by sensitizing Eu3+ via the antenna effect. In addition, combined with the improved rolling circle amplification-assisted strand displacement amplification strategy (RCA-SDA), a sensitive biosensor was constructed for the sensitive detection of miR-221 with a low detection limit of 5.12 aM and could be successfully applied for the detection of miR-221 in the lysate of cancer cells. This strategy offered a unique approach to synthesizing metal-organic gels as ECL emitters without a coreactant for the construction of ECL biosensing platforms in biomarker detection and disease diagnosis.

Nanoconfined Silver Nanoclusters Combined with X-Shaped DNA Recognizer-Triggered Cascade Amplification for Electrochemiluminescence Detection of APE1.

Apurinic/apyrimidinic endonuclease 1 (APE1), as a vital base excision repair enzyme, is essential for maintaining genomic integrity and stability, and its abnormal expression is closely associated with malignant tumors. Herein, we constructed an electrochemiluminescence (ECL) biosensor for detecting APE1 activity by combining nanoconfined ECL silver nanoclusters (Ag NCs) with X-shaped DNA recognizer-triggered cascade amplification. Specifically, the Ag NCs were prepared and confined in the glutaraldehyde-cross-linked chitosan hydrogel network using the one-pot method, resulting in a strong ECL response and exceptional stability in comparison with discrete Ag NCs. Furthermore, the self-assembled X-shaped DNA recognizers were designed for APE1 detection, which not only improved reaction kinetics due to the ordered arrangement of recognition sites but also achieved high sensitivity by utilizing the recognizer-triggered cascade amplification of strand displacement amplification (SDA) and DNAzyme catalysis. As expected, this biosensor achieved sensitive ECL detection of APE1 in the range of 1.0 × 10-3 U·µL-1 to 1.0 × 10-10 U·µL-1 with the detection limit of 2.21 × 10-11 U·µL-1, rendering it a desirable approach for biomarker detection.

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.

Sleep deprivation attenuates neural responses to outcomes from risky decision-making.

Sleep loss impacts a broad range of brain and cognitive functions. However, how sleep deprivation affects risky decision-making remains inconclusive. This study used functional MRI to examine the impact of one night of total sleep deprivation (TSD) on risky decision-making behavior and the underlying brain responses in healthy adults. In this study, we analyzed data from N = 56 participants in a strictly controlled 5-day and 4-night in-laboratory study using a modified Balloon Analogue Risk Task. Participants completed two scan sessions in counter-balanced order, including one scan during rested wakefulness (RW) and another scan after one night of TSD. Results showed no differences in participants' risk-taking propensity and risk-induced activation between RW and TSD. However, participants showed significantly reduced neural activity in the anterior cingulate cortex and bilateral insula for loss outcomes, and in bilateral putamen for win outcomes during TSD compared with RW. Moreover, risk-induced activation in the insula negatively correlated with participants' risk-taking propensity during RW, while no such correlations were observed after TSD. These findings suggest that sleep loss may impact risky decision-making by attenuating neural responses to decision outcomes and impairing brain-behavior associations.

Aggregation-Induced Electrochemiluminescence of Copper Nanoclusters by Regulating Valence State Ratio of Cu(I)/Cu(0) for Ultrasensitive Detection of MicroRNA.

In this work, Cu nanoclusters (Cu NCs) with strong aggregation-induced electrochemiluminescence (AIECL) as emitters were used to construct an ECL biosensor for ultrasensitive detection of microRNA-141 (miR-141). Impressively, the ECL signals enhanced with the increased content of Cu(I) in the aggregative Cu NCs. When the ratio of Cu(I)/Cu(0) in aggregative Cu NCs was 3.2, Cu NCs aggregates showed the highest ECL intensity, in which Cu(I) could enhance the cuprophilic Cu(I)···Cu(I) interaction to form rod-shaped aggregates for restricting nonradiative transitions to obviously improve the ECL response. As a result, the ECL intensity of the aggregative Cu NCs was 3.5 times higher than that of the monodispersed Cu NCs. With the aid of the cascade strand displacement amplification (SDA) strategy, an outstanding ECL biosensor was developed to achieve the ultrasensitive detection of miR-141, whose linear range varied from 10 aM to 1 nM with a detection limit of 1.2 aM. This approach opened an avenue to prepare non-noble metal nanomaterials as robust ECL emitters and provided a new idea for detection of biomolecules for diagnosis of disease.

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.

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.

Controllable Three-Dimensional DNA Nanomachine-Mediated Electrochemical Biosensing Platform for Rapid and Ultrasensitive Detection of MicroRNA.

In this work, a high-efficiency controllable three-dimensional (3D) DNA nanomachine (CDNM) was reasonably developed by regulating the diameter of the core and the length of the DNAzyme cantilever, which acquired greater amplification efficiency and speedier walking rate than traditional 3D DNA nanomachines with gold nanoparticles as the cores and DNAzymes as the walking arms. Significantly, once the target miRNA-21 existed, a large number of silent DNAzymes on the CDNM could be activated by enzyme-free-target-recycling amplification (EFTRA) to achieve fast cleavage and walking on the biosensor surface under the interaction of Mg2+. Impressively, when the diameter of the core was 40 nm and the length of the DNAzyme cantilever was 5 nm (15 bp), the CDNM could complete the reaction process in 60 min that was at least twice shorter than those of conventional DNA nanomachines. Moreover, the designed electrochemical biosensor successfully detected target miRNA-21 at an ultrasensitive level with a wide response range (100 aM to 1 nM) and a low detection limit (33.1 aM). Therefore, the developed CDNM provides a new idea for exploring functional DNA nanomachines in the field of biosensing for applications.

Ligand-Based Shielding Effect Induced Efficient Near-Infrared Electrochemiluminescence of Gold Nanoclusters and Its Sensing Application.

Preparing high-efficiency ECL gold nanoclusters (Au NCs) still faces a serious challenge due to the poor stability of co-reactant radicals in aqueous media. Herein, we report a ligand-based shielding effect induced record near-infrared (λmax = 786 nm) ECL efficiency of ß-cyclodextrin-protected Au NCs (ß-CD-Au NCs) with triethylamine (TEA) as co-reactant. The ligand of ß-CD-Au NCs with a matched hydrophobic cavity could encapsulate TEA driven by host-guest chemistry, which not only allows the generation of TEA• in the cavity to diminish environmental exposure, thus reducing the quenching by dissolved oxygen, water, etc., but also shortens the charge transfer pathway without extensive chemical modification. Density functional theory, 1H NMR spectra, electron paramagnetic resonance, and differential pulse voltammetry studies revealed that the ß-CD ligand-based shielding effect significantly increased the reactivity efficiency of TEA. More importantly, in stark contrast to those of traditional ligand-protected Au NCs, the ECL efficiency of ß-CD-Au NCs enhanced 321-fold versus BSA-Au NCs, 153-fold versus ATT-Au NCs, and 19-fold versus GSH-Au NCs with 1 mM TEA. Therefore, this work provides an in-depth understanding of the crucial role of ligands in enhancing the active co-reactant radical stability for high-efficiency ECL metal NCs to immensely stimulate their promising applications. Using the ß-CD-Au NCs as emitters, a "signal off" ECL sensing platform was constructed to detect noradrenaline as a model target with a lower detection limit of 0.91 nM.

Aluminum(III)-Based Organic Nanofibrous Gels as an Aggregation-Induced Electrochemiluminescence Emitter Combined with a Rigid Triplex DNA Walker as a Signal Magnifier for Ultrasensitive DNA Assay.

Due to effective tackling of the problems of aggregation-caused quenching of traditional ECL emitters, aggregation-induced electrochemiluminescence (AIECL) has emerged as a research hotspot in aqueous detection and sensing. However, the existing AIECL emitters still encounter the bottlenecks of low ECL efficiency, poor biocompatibility, and high cost. Herein, aluminum(III)-based organic nanofibrous gels (AOGs) are used as a novel AIECL emitter to construct a rapid and ultrasensitive sensing platform for the detection of Flu A virus biomarker DNA (fDNA) with the assistance of a high-speed and hyper-efficient signal magnifier, a rigid triplex DNA walker (T-DNA walker). The proposed AOGs with three-dimensional (3D) nanofiber morphology are assembled in one step within about 15 s by the ligand 2,2':6',2″-terpyridine-4'-carboxylic acid (TPY-COOH) and cheap metal ion Al3+, which demonstrates an efficient ECL response and outstanding biocompatibility. Impressively, on the basis of loop-mediated isothermal amplification-generated hydrogen ions (LAMP-H+), the target-induced pH-responsive rigid T-DNA walker overcomes the limitations of conventional single or duplex DNA walkers in walking trajectory and efficiency due to the entanglement and lodging of leg DNA, exhibiting high stability, controllability, and walking efficiency. Therefore, AOGs with excellent AIECL performance were combined with a CG-C+ T-DNA nanomachine with high walking efficiency and stability, and the proposed "on-off" ECL biosensor displayed a low detection limit down to 23 ag·µL-1 for target fDNA. Also, the strategy provided a useful platform for rapid and sensitive monitoring of biomolecules, considerably broadening its potential applications in luminescent molecular devices, clinical diagnosis, and sensing analysis.

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.

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.

Zn2+-Induced Gold Cluster Aggregation Enhanced Electrochemiluminescence for Ultrasensitive Detection of MicroRNA-21.

Herein, Zn2+-induced gold cluster aggregation (Zn2+-GCA) as a high-efficiency electrochemiluminescence (ECL) emitter is first employed to construct an ECL biosensor to ultrasensitively detect microRNA-21 (miRNA-21). Impressively, Zn2+ not only can induce the aggregation of monodispersed gold clusters (Au NCs) to limit the ligand vibration of Au NCs for improving ECL emission but also can be utilized as a coreaction accelerator to catalyze the dissociation of coreactant S2O82- into sulfate radicals (SO4•-) to improve the interaction efficiency between Zn2+-GCA and S2O82-, resulting in further intense ECL emission. Compared to Au NCs stabilized by bovine serum albumin with ECL efficiency of 0.40%, Zn2+-GCA possessed high ECL efficiency of 10.54%, regarding the [Ru(bpy)3]2+/S2O82- system as a standard. Furthermore, output DNA modified with poly adenine (polyA) obtained from enzyme-free target recycling amplification can be efficiently immobilized on the surface of gold nanoparticles (Au NPs) to reduce the defect of special design, cumbersome operation, and low stability. Thus, an ultrasensitive ECL biosensor based on the Zn2+-GCA/S2O82- ECL system and enzyme-free target recycling amplification achieved ultrasensitive detection of miRNA-21 with the detection limit of 44.7 aM. This strategy presents a new idea to design highly efficient ECL emitters, which is expected to be used in the field of bioanalysis for clinical diagnosis.

Nitrogen-, Sulfur-, and Fluorine-Codoped Carbon Dots with Low Excitation Potential and High Electrochemiluminescence Efficiency for Sensitive Detection of Matrix Metalloproteinase-2.

In this study, nitrogen-, sulfur-, and fluorine-codoped carbon dots (NSF-CDs) with high electrochemiluminescence (ECL) efficiency were developed as novel emitters to fabricate an ECL biosensor for sensitive detection of matrix metalloproteinase 2 (MMP-2). Impressively, compared to previously reported CDs, NSF-CDs with narrow band gap not only decreased the excitation voltage to reduce the side reaction and the damage on biomolecules but also had hydrogen bonds to vastly enhance the ECL efficiency. Furthermore, an improved exonuclease III (Exo III)-assisted nucleic acid amplification method was established to convert trace MMP-2 into a mass of output DNA, which greatly improved the target conversion efficiency and ECL signal. Hence, the ECL biosensor has realized the sensitive detection of MMP-2 proteins from 10 fg/mL to 10 ng/mL with a limit of detection of 6.83 fg/mL and has been successfully applied in the detection of MMP-2 from Hela and MCF-7 cancer cells. This strategy offered neoteric CDs as ECL emitters for sensitive testing of biomarkers in medical research.

Ultrasensitive Electrochemiluminescence Biosensor Based on 2D Co3O4 Nanosheets as a Coreaction Accelerator and Highly Ordered Rolling DNA Nanomachine as a Signal Amplifier for the Detection of MicroRNA.

A novel ultrasensitive electrochemiluminescence (ECL) biosensor was constructed using two-dimensional (2D) Co3O4 nanosheets as a novel coreaction accelerator of the luminol/H2O2 ECL system for the detection of microRNA-21 (miRNA-21). Impressively, coreaction accelerator 2D Co3O4 nanosheets with effective mutual conversion of the Co2+/Co3+ redox pair and abundant active sites could promote the decomposition of coreactant H2O2 to generate more superoxide anion radicals (O2•-), which reacted with luminol for significantly enhancing ECL signals. Furthermore, the trace target miRNA-21 was transformed into a large number of G-wires through the strand displacement amplification (SDA) process to self-assemble the highly ordered rolling DNA nanomachine (HORDNM), which could tremendously improve the detection sensitivity of biosensors. Hence, on the basis of the novel luminol/H2O2/2D Co3O4 nanosheet ternary ECL system, the biosensor implemented ultrasensitive detection of miRNA-21 with a detection limit as low as 4.1 aM, which provided a novel strategy to design an effective ECL emitter for ultrasensitive detection of biomarkers for early disease diagnosis.