Garnet secondary ion mass spectrometry oxygen isotopes reveal crucial roles of pulsed magmatic fluid and its mixing with meteoric water in lode gold genesis.

SignificanceThere is a common consensus that lode gold deposits mostly precipitated from metamorphic fluids via fluid boiling and/or fluid-rock interaction, but whether magmatic hydrothermal fluids and the mixing of such fluids with an external component have played a vital role in the formation of lode gold deposits remains elusive. We use garnet secondary ion mass spectrometry oxygen isotope analysis to demonstrate that the world-class Dongping lode gold deposit has been formed by multiple pulses of magmatic hydrothermal fluids and their mixing with large volumes of meteoric water. This study opens an opportunity to tightly constrain the origin of lode gold deposits worldwide and other hydrothermal systems that may have generated giant ore deposits in the Earth's crust.

Click Conjugation of Zwitterionic Peptide with DNA Strand: An Efficient Antifouling Strategy for Versatile Photoelectrochemical Aptasensor.

Advanced antifouling biosensors have garnered considerable attention for their potential for precise and sensitive analysis in complex human bodily fluids. Herein, a pioneering approach was utilized to establish a robust and versatile photoelectrochemical aptasensor by conjugating a zwitterionic peptide with a DNA strand. Specifically, the branched zwitterionic peptide (BZP) was efficiently linked to complementary DNA (cDNA) through a click reaction, forming the BZP-cDNA conjugate. This intriguing conjugate exploited the BZP domain to create an antifouling biointerface, while the cDNA component facilitated subsequent hybridization with probe DNA (pDNA). To advance the development of the aptasensor, an upgraded PDA/HOF-101/ZnO ternary photoelectrode was designed as the signal converter for the modification of the BZP-cDNA conjugate, while a bipyridinium (MCEPy) molecule with strong electron-withdrawing properties was labeled at the front end of the pDNA to form the pDNA-MCEPy signal probe. Targeting the model of mucin-1, a remarkable enhancement in the photocurrent signal was achieved through exonuclease-I-aided target recycling. Such an engineered zwitterionic peptide-DNA conjugate surpasses the limitations imposed by conventional peptide-based sensing modes, exhibiting unique advantages such as versatility in design and capability for signal amplification.

Highly Light-Harvesting MOF-on-MOF Heterostructure: Cascading Functionality to Flexible Photogating of Organic Photoelectrochemical Transistor and Bienzyme Cascade Detection.

Recently, organic photoelectrochemical transistor (OPECT) bioanalysis has become a prominent technique for the high-performance detection of biomolecules. However, as a sensitive index of the OPECT, the dynamic regulation transconductance (gm) is still severely deficient. Herein, this work reports a new photosensitive metal-organic framework (MOF-on-MOF) heterostructure for the effective modulation of maximum gm and natural bienzyme interfacing toward choline detection. Specifically, the bidentate ligand MOF (b-MOF) was assembled onto the UiO-66 MOF (u-MOF) by a modular assembly method, which could facilitate the charge separation and generate enhanced photocurrents and offer a biophilic environment for the immobilization of choline oxidase (ChOx) and horseradish peroxidase (HRP) through hydrogen-bonded bridges. The transconductance of the OPECT could be flexibly altered by increased light intensity to maximal value at zero gate bias, and sensitive choline detection was achieved with a detection limit of 0.2 µM. This work reveals the potential of MOF-on-MOF heterostructures for futuristic optobioelectronics.

Intelligent Cell Profiling and Precision Release: Multimolecular Marker-Activated Transmembrane DNA Computing Nanosystem.

Accurate classification of tumor cells is of importance for cancer diagnosis and further therapy. In this study, we develop multimolecular marker-activated transmembrane DNA computing systems (MTD). Employing the cell membrane as a native gate, the MTD system enables direct signal output following simple spatial events of "transmembrane" and "in-cell target encounter", bypassing the need of multistep signal conversion. The MTD system comprises two intelligent nanorobots capable of independently sensing three molecular markers (MUC1, EpCAM, and miR-21), resulting in comprehensive analysis. Our AND-AND logic-gated system (MTDAND-AND) demonstrates exceptional specificity, allowing targeted release of drug-DNA specifically in MCF-7 cells. Furthermore, the transformed OR-AND logic-gated system (MTDOR-AND) exhibits broader adaptability, facilitating the release of drug-DNA in three positive cancer cell lines (MCF-7, HeLa, and HepG2). Importantly, MTDAND-AND and MTDOR-AND, while possessing distinct personalized therapeutic potential, share the ability of outputting three imaging signals without any intermediate conversion steps. This feature ensures precise classification cross diverse cells (MCF-7, HeLa, HepG2, and MCF-10A), even in mixed populations. This study provides a straightforward yet effective solution to augment the versatility and precision of DNA computing systems, advancing their potential applications in biomedical diagnostic and therapeutic research.

Atherosclerosis is associated with plasma Aß levels in non-hypertension patients.

BACKGROUND: Growing evidence indicated that to develop of atherosclerosis observed more often by people with Alzheimer's disease (AD), but the underlying mechanism is not fully clarified. Considering that amyloid-ß (Aß) deposition in the brain is the key pathophysiology of AD and plasma Aß is closely relate to Aß deposition in the brain, in the present study, we investigated the relationships between atherosclerosis and plasma Aß levels. METHODS: This was a population based cross-sectional study. Patients with high risk of atherosclerosis from Qubao Village, Xi'an were underwent carotid ultrasound for assessment of atherosclerosis. Venous blood was collected on empty stomach in the morning and plasma Aß1-40 and Aß1-42 levels were measured using ELISA. Multivariate logistic regression analysis was performed to investigate the relationships between carotid atherosclerosis (CAS) and plasma Aß levels. RESULTS: Among 344 patients with high risk of atherosclerosis, 251(73.0%) had CAS. In the univariate analysis, the plasma Aß levels had no significant differences between CAS group and non-CAS group (Aß1-40: 53.07 ± 9.24 pg/ml vs. 51.67 ± 9.11pg/ml, p = 0.211; Aß1-42: 40.10 ± 5.57 pg/ml vs. 40.70 pg/ml ± 6.37pg/ml, p = 0.285). Multivariate logistic analysis showed that plasma Aß levels were not associated with CAS (Aß1-40: OR = 1.019, 95%CI: 0.985-1.054, p = 0.270;Aß1-42: OR = 1.028, 95%CI: 0.980-1.079, p = 0.256) in the total study population. After stratified by hypertension, CAS was associated with plasma Aß1-40 positively (OR = 1.063, 95%CI: 1.007-1.122, p = 0.028) in the non-hypertension group, but not in hypertensive group. When the plasma Aß concentrations were classified into four groups according to its quartile, the highest level of plasma Aß1-40 group was associated with CAS significantly (OR = 4.465, 95%CI: 1.024-19.474, p = 0.046). CONCLUSION: Among patients with high risk of atherosclerosis, CAS was associated with higher plasma Aß1-40 level in non-hypertension group, but not in hypertension group. These indicated that atherosclerosis is associated with plasma Aß level, but the relationship may be confounded by hypertension.

Heat shock protein 90 and prolyl hydroxylase 2 co-regulate hypoxia-inducible factor-1α expression in porcine small intestinal epithelial cells under heat stress.

Heat stress (HS) poses a substantial threat to animal growth and development, resulting in declining performance and economic losses. The intestinal system is susceptible to HS and undergoes intestinal hyperthermia and pathological hypoxia. Hypoxia-inducible factor-1α (HIF-1α), a key player in cellular hypoxic adaptation, is influenced by prolyl-4-hydroxylase 2 (PHD2) and heat shock protein 90 (HSP90). However, the comprehensive regulation of HIF-1α in the HS intestine remains unclear. This study aims to explore the impact of HS on pig intestinal mucosa and the regulatory mechanism of HIF-1α. Twenty-four Congjiang Xiang pigs were divided into the control and five HS-treated groups (6, 12, 24, 48, and 72 h). Ambient temperature and humidity were maintained in a thermally-neutral state (temperature-humidity index (THI) < 74) in the control group, whereas the HS group experienced moderate HS (78 < THI <84). Histological examination revealed villus exfoliation after 12 h of HS in the duodenum, jejunum, and ileum, with increasing damage as HS duration extended. The villus height to crypt depth ratio (V/C) decreased and goblet cell number increased with prolonged HS. Quantitative real-time PCR, Western blot, and immunohistochemistry analysis indicated increased expression of HIF-1α and HSP90 in the small intestine with prolonged HS, whereas PHD2 expression decreased. Further investigation in IPEC-J2 cells subjected to HS revealed that overexpressing PHD2 increased PHD2 mRNA and protein expression, while it decreases HIF-1α. Conversely, interfering with HSP90 expression substantially decreased both HSP90 and HIF-1α mRNA and protein levels. These results suggest that HS induces intestinal hypoxia with concomitant small intestinal mucosal damage. The expression of HIF-1α in HS-treated intestinal epithelial cells may be co-regulated by HSP90 and PHD2 and is possibly linked to intestinal hyperthermia and hypoxia.

Engineered Branching Peptide as Dual-Functional Antifouling and Recognition Probe: Toward a Dual-Photoelectrode Protein Biosensor with High Accuracy.

The building of practical biosensors that have anti-interference abilities against biofouling of nonspecific proteins and biooxidation of reducing agents in actual biological matrixes remains a great challenge. Herein, a robust photoelectrochemical (PEC) biosensor capable of accurate detection in human serum was pioneered through the integration of a new engineered branching peptide (EBP) into a synergetic dual-photoelectrode system. The synergetic dual-photoelectrode system involved the tandem connection of a C3N4/TiO2 photoanode and a AuPt/PANI photocathode, while the EBP as a dual-functional antifouling and recognition probe featured an inverted Y-shaped configuration with one recognition backbone and two antifouling branches. Such an EBP enables a simple procedure for electrode modification and an enhanced antifouling nature compared to a regular linear peptide (LP), as theoretically supported by the results from molecular dynamics simulations. The as-developed PEC biosensor had a higher photocurrent response and a good antioxidation property inherited from the photoanode and photocathode, respectively. Targeting the model protein biomarker of cardiac troponin I (cTnI), this biosensor achieved good performances in terms of high sensitivity, specificity, and anti-interference.

Synergistic Incorporation of Two ssDNA Activators Enhances the Trans-Cleavage of CRISPR/Cas12a.

CRISPR/Cas12a has been believed to be powerful in molecular detection and diagnostics due to its amplified trans-cleavage feature. However, the activating specificity and multiple activation mechanisms of the Cas12a system are yet to be elucidated fully. Herein, a "synergistic activator effect" is discovered, which supports an activation mechanism that a synergistic incorporation of two short ssDNA activators can promote the trans-cleavage of CRISPR/Cas12a, while either of them is too short to work independently. As a proof-of-concept example, the synergistic activator-triggered CRISPR/Cas12a system has been successfully harnessed in the AND logic operation and the discrimination of single-nucleotide variants, requiring no signal conversion elements or other amplified enzymes. Moreover, a single-nucleotide specificity has been achieved for the detection of single-nucleotide variants by pre-introducing a synthetic mismatch between crRNA and the "helper" activator. The finding of "synergistic activator effect" not only provides deeper insight into CRISPR/Cas12a but also may facilitate its expanded application and power the exploration of the undiscovered properties of other CRISPR/Cas systems.

Compute-and-Release Logic-Gated DNA Cascade Circuit for Accurate Cancer Cell Imaging.

Accurate identification of cancer cells is an essential prerequisite for cancer diagnosis and subsequent effective curative interventions. The logic-gate-assisted cancer imaging system that allows a comparison of expression levels between biomarkers, rather than just reading biomarkers as inputs, returns a more comprehensive logical output, improving its accuracy for cell identification. To fulfill this key criterion, we develop a compute-and-release logic-gated double-amplified DNA cascade circuit. This novel system, CAR-CHA-HCR, consists of a compute-and-release (CAR) logic gate, a double-amplified DNA cascade circuit (termed CHA-HCR), and a MnO2 nanocarrier. CAR-CHA-HCR, a novel adaptive logic system, is designed to logically output the fluorescence signals after computing the expression levels of intracellular miR-21 and miR-892b. Only when miR-21 is present and its expression level is above the threshold CmiR-21 > CmiR-892b, the CAR-CHA-HCR circuit performs a compute-and-release operation on free miR-21, thereby outputting enhanced fluorescence signals to accurately image positive cells. It is capable of comparing the relative concentrations of two biomarkers while sensing them, thus allowing accurate identification of positive cancer cells, even in mixed cell populations. Such an intelligent system provides an avenue for highly accurate cancer imaging and is potentially envisioned to perform more complex tasks in biomedical studies.

piRNA-30473 contributes to tumorigenesis and poor prognosis by regulating m6A RNA methylation in DLBCL.

The initiation and progression of diffuse large B-cell lymphoma (DLBCL) is governed by genetic and epigenetic aberrations. As the most abundant eukaryotic messenger RNA (mRNA) modification, N6-methyladenosine (m6A) is known to influence various fundamental bioprocesses by regulating the target gene; however, the function of m6A modifications in DLBCL is unclear. PIWI-interacting RNAs (piRNAs) have been indicated to be epigenetic effectors in cancer. Here, we show that high expression of piRNA-30473 supports the aggressive phenotype of DLBCL, and piRNA-30473 depletion decreases proliferation and induces cell cycle arrest in DLBCL cells. In xenograft DLBCL models, piRNA-30473 inhibition reduces tumor growth. Moreover, piRNA-30473 is significantly associated with overall survival in a univariate analysis and is statistically significant after adjusting for the National Comprehensive Cancer Network-International Prognostic Index in the multivariate analysis. Additional studies demonstrate that piRNA-30473 exerts its oncogenic role through a mechanism involving the upregulation of WTAP, an m6A mRNA methylase, and thus enhances the global m6A level. Integrating transcriptome and m6A-sequencing analyses reveals that WTAP increases the expression of its critical target gene, hexokinase 2 (HK2), by enhancing the HK2 m6A level, thereby promoting the progression of DLBCL. Together, the piRNA-30473/WTAP/HK2 axis contributes to tumorigenesis by regulating m6A RNA methylation in DLBCL. Furthermore, by comprehensively analyzing our clinical data and data sets, we discover that the m6A regulatory genes piRNA-30473 and WTAP improve survival prediction in DLBCL patients. Our study highlights the functional importance of the m6A modification in DLBCL and might assist in the development of a prognostic stratification and therapeutic approach for DLBCL.

Recent advances of the ionic chiral selectors for chiral resolution by chromatography, spectroscopy and electrochemistry.

Ionic chiral selectors have been received much attention in the field of asymmetric catalysis, chiral recognition, and preparative separation. It has been shown that the addition of ionic chiral selectors can enhance the recognition efficiency dramatically due to the presence of multiple intermolecular interactions, including hydrogen bond, π-π interaction, van der Waals force, electrostatic ion-pairing interaction, and ionic-hydrogen bond. In the initial research stage of the ionic chiral selectors, most of work center on the application in chromatographic separation (capillary electrophoresis, high-performance liquid chromatography, and gas chromatography). Differently, more and more attention has been paid on the spectroscopy (nuclear magnetic resonance, fluorescence, ultraviolet and visible absorption spectrum, and circular dichroism spectrum) and electrochemistry in recent years. In this tutorial review as regards the ionic chiral selectors, we discuss in detail the structural features, properties, and their application in chromatography, spectroscopy, and electrochemistry.

Downregulation of ITGA6 confers to the invasion of multiple myeloma and promotes progression to plasma cell leukaemia.

BACKGROUND: Secondary plasma cell leukaemia (sPCL) is an aggressive form of multiple myeloma (MM), but the mechanism underlying MM progresses into PCL remains unknown. METHODS: Gene expression profiling of MM patients and PCL patients was analysed to identify the molecular differences between the two diseases. Cox survival regression and Kaplan-Meier analysis were performed to illustrate the impact of integrin subunit alpha 6 (ITGA6) on prognosis of MM. Invasion assays were performed to assess whether ITGA6 regulated the progression of MM to PCL. RESULTS: Gene expression profiling analyses showed that cell metastasis pathways were enriched in PCL and ITGA6 was differentially expressed between PCL and MM. ITGA6 expression was an independent prognostic factor for event-free survival (EFS) and overall survival (OS) of MM patients. Moreover, the stratification ability of the International Staging System (ISS) of MM was improved when including ITGA6 expression. Functional studies uncovered that increased ITGA6 reduced the myeloma cell invasion. Additionally, low expression of ITGA6 resulted from epigenetic downregulating of its anti-sense non-coding RNA, ITGA6-AS1. CONCLUSION: Our data reveal that ITGA6 gradually decreases during plasma cell dyscrasias progression and low expression of ITGA6 contributes to myeloma metastasis. Moreover, ITGA6 abundance might help develop MM prognostic stratification.

Peptide-Based Photocathodic Biosensors: Integrating a Recognition Peptide with an Antifouling Peptide.

Accurate and sensitive detection of targets in practical biological matrixes such as blood, plasma, serum, or tissue fluid is a frontier issue for most biosensors since the coexistence of both potential reducing agents and protein molecules has the possibility of causing signal interference. Herein, aiming at detection in a complex environment, an advanced and robust peptide-based photocathodic biosensor, which integrated a recognition peptide with an antifouling peptide in one probe electrode, was first proposed. Selecting human chorionic gonadotropin (hCG) as a model target, the recognition peptide with the sequence PPLRINRHILTR was first anchored on the CuBi2O4/Au (CBO/Au) photocathode and then the antifouling peptide with the sequence EKEKEKEPPPPC was further anchored to generate an antifouling biointerface. The peptide-based photocathodic biosensor demonstrated excellent anti-interference to both nonspecific proteins and reducing agents because of the capability of the antifouling peptide. It also exhibited good sensitivity owing to the utilization of the recognition peptide rather than an antibody probe. This peptide-integrated method offers a new perspective for practical applications of photocathodic biosensors.

Covalent Amide-Bonded Nanoflares for High-Fidelity Intracellular Sensing and Targeted Therapy: A Superstable Nanosystem Free of Nonspecific Interferences.

A nanoflare, a conjugate of Au nanoparticles (NPs) and fluorescent nucleic acids, is believed to be a powerful nanoplatform for diagnosis and therapy. However, it highly suffers from the nonspecific detachment of nucleic acids from the AuNP surface because of the poor stability of Au-S linkages, thereby leading to the false-positive signal and serious side effects. To address these challenges, we report the use of covalent amide linkage and functional Au@graphene (AuG) NP to fabricate a covalent conjugate system of DNA and AuG NP, label-rcDNA-AuG. Covalent coating of abundant amino groups (-NH2) onto the graphitic shell of AuG NP efficiently facilitates the coupling with carboxyl-labeled capture DNA sequences through simple, but strong, amide bonds. Importantly, such an amide-bonded nanoflare possesses excellent stability and anti-interference capability against the biological agents (nuclease, DNA, glutathione (GSH), etc.). By accurately monitoring the intracellular miR-21 levels, this covalent nanoflare is able to identify the positive cancer cells even in a mix of cancer and normal cells. Moreover, it allows for efficient photodynamic therapy of the targeted cancer cells with minimized side effects on normal cells. This work provides a facile approach to develop a superstable nanosystem showing promising potential in clinical diagnostics and therapy.

A portable SERS reader coupled with catalytic hairpin assembly for sensitive microRNA-21 lateral flow sensing.

Nucleic acid lateral flow sensing has drawn great research attention since it has the advantages of being simple, rapid, and cost-effective. However, considering the trace amounts of the nucleic acid targets, its sensitivity is still limited. Although enormous efforts have been devoted to enhancing its sensitivity, developing a simple lateral flow sensing platform with high sensitivity remains challenging. We report a novel lateral flow microRNA-21 biosensing platform based on a portable surface enhanced Raman scattering (SERS) reader coupled with a catalytic hairpin assembly signal amplification strategy. Hairpin DNA probes were anchored on Au@Ag nanotags, and the presence of microRNA-21 triggered the formation of numerous double-stranded DNAs along with the exposure of the biotin groups. By this means, the target was recycled and signal amplification was achieved. The Au@Ag nanoprobes with exposed biotin can be captured on the test line via its interaction with streptavidin. By scanning the strip with a portable SERS reader, the sensitive quantification of microRNA-21 was realized with a detection limit as low as 84 fM. The proposed strategy was employed to detect the target in a serum sample, demonstrating its great potential in amplified point-of-care biosensing for clinical diagnosis.

Silver nanoparticle driven signal amplification for electrochemical chiral discrimination of amino acids.

ß-Cyclodextrin (ß-CD) modified silver nanoparticles (AgNPs), denoted as ß-CD/AgNPs, were prepared by a simple one-pot method. Due to the inherent chirality of ß-CD, the developed ß-CD/AgNPs exhibited higher affinity toward l-tyrosine (l-Tyr) than d-tyrosine (d-Tyr), leading to serious aggregation of AgNPs in the presence of l-Tyr. Consequently, the l-Tyr induced aggregation of AgNPs can result in signal amplification in the differential pulse voltammograms (DPVs) of l-Tyr, which can be applied for the electrochemical chiral discrimination of the Tyr enantiomers. Other chiral amino acids including tryptophan and phenylalanine can also be successfully discriminated with the ß-CD/AgNPs, suggesting high universality of the developed chiral sensor.

Shell-Switchable SERS Blocking Strategy for Reliable Signal-On SERS Sensing in Living Cells: Detecting an External Target without Affecting the Internal Raman Molecule.

For SERS analysis in living cells, the inevitable desorption of Raman molecule on the substrate surface is a key challenge. To ensure high stability, SERS systems with Raman molecules protected inside the core-Raman molecule-shell (C-M-S) structures have been designed, but at the expense of sacrificed sensing performances. Here a shell-switchable SERS blocking strategy is developed for the reliable SERS analysis in living cells, relying on the shell blockers to regulate the SERS sensing signal without affecting the internal Raman molecules. After several C-M-S structures were investigated, the SERS blocking mechanism confirmed that thick shells (Au, Ag, ZnO, and MnO2) can cause a significant reduction in the internal SERS signal by obstructing the penetration of the laser or signal. The CAu-Mpy-SAu-SMnO2 nanoprobe is designed for the ratiometric SERS sensing in living cells, which retains sensing performances even though the Raman molecule is protected inside the nanostructure. This SERS strategy makes the turn-on sensing achievable in living cells with the MnO2 shell as a signal switch and a Raman reference. Additionally, it allows for accurate monitoring of the degradation of MnO2 carriers in living cells, even without fluorescent labels.

HOXC10 Regulates Osteogenesis of Mesenchymal Stromal Cells Through Interaction with Its Natural Antisense Transcript lncHOXC-AS3.

The characteristics of mesenchymal stromal cells (MSCs) which derived from multiple myeloma (MM) patients are typically impaired in osteogenic differentiation. However, the underlying molecular mechanisms need to be further investigated. lncRNAs are emerging as critical regulation molecules in oncogenic pathways. In this study, we identified that bioactive lncRNA HOXC-AS3, which is transcribed in opposite to HOXC10, was presented in MSCs derived from bone marrow (BM) of MM patients (MM-MSCs). HOXC-AS3 was able to interact with HOXC10 at the overlapping parts and this interaction increased HOXC10 stability, then promoted its expression, conferring osteogenesis repression to MM-MSCs. In mouse models, intravenously administered siHOXC-AS3 was proven to be effective in prevention of bone loss, sustained by both anticatabolic activities and bone-forming. These data showed that lncHOXC-AS3 was required for osteogenesis in BM-MSCs by enhancing HOXC10 expression. Our finding thus unveils a novel insight for the potential clinical significance of lncRNA HOXC-AS3 as a therapeutic target for bone disease in MM. Stem Cells 2019;37:247-256.

Gold Nanoparticle-Induced Photocurrent Quenching and Recovery of Polymer Dots: Toward Signal-On Energy-Transfer-Based Photocathodic Bioanalysis of Telomerase Activity in Cell Extracts.

Energy transfer (ET) in photoelectrochemical (PEC) bioanalysis is usually generated between noble metal nanoparticles (NPs) and traditional inorganic quantum dots (QDs). Using the innovative polymer dot (Pdot)-involved ET, this work reports the first signal-on and cathodic PEC bioanalysis toward telomerase (TE) activity in cell extracts. Specifically, the sequential binding of capture DNA (cDNA), telomerase primer sequence (TS), and Au NP-labeled probe DNA (Au NP-pDNA) on the electrode would place the Au NPs in close proximity of the Pdots, leading to obvious quenching of the cathodic photocurrent. The subsequent extension of the TS by TE in the presence of deoxyribonucleoside triphosphates (dNTPs) would then release the Ag NP-pDNA from the electrode, leading to the recovery of the photocurrent. On the basis of the Au NP-induced photocurrent quenching and the recovery of Pdots, a sensitive biosensor could thus be developed by tracking the photocurrents to probe the TE activity. This strategy allows for signal-on and cathodic PEC bioanalysis of TE, which can be easily extended for numerous other targets of interest. We believe this work could offer a new perspective for the rational implementation of Pdot-involved ET for advanced PEC bioanalysis.

Plasmon Coupling-Enhanced Raman Sensing Platform Integrated with Exonuclease-Assisted Target Recycling Amplification for Ultrasensitive and Selective Detection of microRNA-21.

A "signal-off" surface-enhanced Raman scattering (SERS) platform has been constructed for ultrasensitive detection of miRNA-21 by integrating exonuclease-assisted target recycling amplification with a plasmon coupling enhancement effect. On this platform, Raman-labeled Au nanostar (AuNS) probes can be covalently linked with the thiolated aptamer (Apt) on the Au-decorated silicon nanowire arrays (SiNWAs/Au) substrate, creating a coupled electromagnetic field between the substrate and the probes to enhance Raman signal. In the presence of miRNA-21, T7 exonuclease specifically hydrolyzed Apt on Apt/miRNA duplex to release miRNA-21. The regenerated element could then initiate another cycle of Apt/miRNA duplex formation and Apt cleavage. Correspondingly, the capture ability of substrate toward probes and the plasmon coupling effect between them were both diminished, giving a prominent attenuation of Raman intensity that can work as the detection signal. Due to the cascading integration between the target cycle process and the plasmon coupling effect, the present platform displayed a very low detection limit (0.34 fM, 3σ) for miRNA-21 detection. Furthermore, it was proven to be effective for analyzing miRNA-21 in biological samples and distinguishing the expression levels of miRNA-21 in MCF-7 cells and NIH3T3 cells, which became a promising tool to monitor miRNA-21 in cancer auxiliary diagnosis and drug screening.