A colorimetric sensor for rapid discrimination of tea polyphenols and tea authentication based on Rh-decorated Pd nanocubes with high peroxidase-like activity.

The rapid development of nanozymes has offered substantial opportunities for the fields of biomedicine, chemical sensing, and food safety. Among these applications, multichannel sensors, with the capability of simultaneously detecting multiple target analytes, hold promise for the practical application of nanozymes in chemical sensing with high detection efficiency. In this study, Rh-decorated Pd nanocubes (Pd-Rh nanocubes) with significantly enhanced peroxidase-like activity are synthesized through the mediation of underpotential deposition (UPD) and subsequently employed to develop a multichannel colorimetric sensor for discriminating tea polyphenols (TPs) and tea authentication. Based on a single reactive unit of efficient catalytic oxidation of 3,3',5,5'-tetramethylbenzidine dihydrochloride (TMB), the nanozyme-based multichannel colorimetric sensor responds to each analyte in as short as 1 min. With the aid of principal component analysis (PCA) and hierarchical cluster analysis (HCA), various TPs and types of tea can be accurately identified. This work not only provides a new type of simply structured and highly active nanozymes but also develops a concise and rapid multichannel sensor for practical application in tea authentication and quality inspection.

Novel insights into macrophage immunometabolism in nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH), an inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis, and has been becoming the leading cause of liver-related morbidity and mortality worldwide. Unfortunately, the pathogenesis of NASH has not been completely clarified, and there are no approved therapeutic drugs. Recent accumulated evidences have revealed the involvement of macrophage in the regulation of host liver steatosis, inflammation and fibrosis, and different phenotypes of macrophages have different metabolic characteristics. Therefore, targeted regulation of macrophage immunometabolism may contribute to the treatment and prognosis of NASH. In this review, we summarized the current evidences of the role of macrophage immunometabolism in NASH, especially focused on the related function conversion, as well as the strategies to promote its polarization balance in the liver, and hold promise for macrophage immunometabolism-targeted therapies in the treatment of NASH.

A validated LC-MS/MS method for the quantitation of daratumumab in rat serum using rapid tryptic digestion without IgG purification and reduction.

Daratumumab, a humanized monoclonal antibody utilized in treating immunoglobulin light-chain amyloidosis and relapsed/refractory multiple myeloma, was quantified in rat serum through a simple, economical and effective liquid chromatography tandem-mass spectrometry (LC-MS/MS) method. A surrogate peptide, LLIYDASNR, derived from trypsin hydrolysis, was quantitatively analyzed with LLIYDASN [13C6, 15N4] RAT as an internal standard. This corrected variations from sample pretreatment and mass spectrometry response, involving denaturation and trypsin hydrolysis in a two-step process lasting approximately 1 hour. Methodological validation demonstrated a linear range of 1 µg/mL to 1000 µg/mL in rat serum. Precision, accuracy, matrix effect, sensitivity, stability, selectivity, carryover, and interference met acceptance criteria. The validated LC-MS/MS approach was successfully applied to a pharmacokinetic study of daratumumab in rats at an intravenous dose of 15 mg/kg.

Covalent organic frame based high-performance nanocomposite for construction of ATP sensor.

In this work, a novel covalent organic frame (TAPT-TFPB COF) with self-enhanced photoelectric activity was prepared for decorating on conductive single-walled carbon nanotubes (SWCNT) to synthetize a high-performance photoelectric nanocomposite (COF/SWCNT), in which the interfacial charge separation and photogenerated carrier migration rate was significantly improved to obtain desiring photoelectric conversion efficiency for generating an extremely high photocurrent. Accordingly, the synthetic COF/SWCNT was ingeniously applied in the fabrication of ultrasensitive photoelectrochemical (PEC) biosensor for realizing the trace ATP detection by integrating with an Exo III-assisted dual DNA recycling amplification strategy. The recycling amplification could efficiently convert trace target ATP into plentiful output DNA, which ingeniously triggered the hybridization chain reaction (HCR) to generate a long DNA strand with substantial quencher manganese porphyrin (MnPP) loading to depress the photocurrent of COF/SWCNT. The experimental data showed that proposed biosensor had a detection range from 10 fmol L-1 to 10 nmol L-1 with the detection limit as low as 2.75 fmol L-1 (S/N = 3). In addition, this proposed biosensor showed excellent analytical performance in terms of stability, specificity and reproducibility, providing a possibility to accomplish sensitive and accurate in vitro diagnosis.

A robust and validated LC-MS/MS method for the quantification of ramucirumab in rat and human serum using direct enzymatic digestion without immunoassay.

A new liquid chromatography tandem mass spectrometry (LC-MS/MS) method was established to quantify the anti-gastric cancer fully human monoclonal antibody (ramucirumab) in rat and human serum. The surrogate peptide (GPSVLPLAPSSK) for ramucirumab was generated by trypsin hydrolysis and quantified using the isotopically labeled peptide GPSVLPLAPSSK[13C6, 15N2]ST containing two more amino acids at the carboxyl end as an internal standard to correct for variations introduced during the enzymatic hydrolysis process and any mass spectrometry changes. Additionally, the oxidation and deamidation of unstable peptides (VVSVLTVLHQDWLNGK and NSLYLQMNSLR) were detected. The quantitative range of the proposed method was 1-1000 µg/mL, and complete methodological validation was performed. The precision, accuracy, matrix effect, sensitivity, stability, selectivity, carryover, and interference of the measurements met the required standards. The validated LC-MS/MS method was applied to pharmacokinetic studies in rats administered ramucirumab at 15 mg/kg intravenously. Overall, a robust, efficient, and cost-effective LC-MS/MS method was successfully developed for quantifying ramucirumab in rat and human serum.

Metabolite characterisation of the peptide-drug conjugate LN005 in liver S9s by UHPLC-Orbitrap-HRMS.

LN005 is a peptide-drug conjugate (PDC) targeting glucose-regulated protein 78 (GRP78) to treat several types of cancer, such as breast, colon, and prostate cancer.As a new drug modality, understanding its metabolism and elimination pathways will help us to have a whole picture of it. Currently, there are no metabolic studies on LN005; therefore, this study aimed to investigate the metabolism of LN005, clarify its metabolic profile in the liver S9s of different species, and identify the major metabolic pathways and differences between species.The incubation samples were measured by ultra-high performance liquid chromatography combined with orbitrap tandem mass spectrometry (UHPLC-Orbitrap-HRMS).The results showed that LN005 was metabolised by liver S9s, and four metabolites were identified. The main metabolic pathway of LN005 in liver S9s was oxidative deamination to ketone or hydrolysis. Similar metabolic profiles were observed in mouse, rat, dog, monkey, and human liver S9s, indicating no differences between these four animal species and humans.This study provides information for the structural modification and optimisation of LN005 and affords a reference for subsequent animal experiments and human metabolism of other PDCs.

Novel Porphyrinic Covalent Organic Polymer with Polarity-Switchable Dual Wavelength for Accurate and Sensitive Photoelectrochemical Sensing.

Herein, we synthesized a novel porphyrinic covalent organic polymer (TPAPP-PTCA PCOP) for constructing a polarity-switchable dual-wavelength photoelectrochemical (PEC) biosensor with ferrocene (Fc) and hydrogen peroxide (H2O2) as regulator and amplifier simultaneously. Interestingly, this new PCOP possessed both n-type and p-type semiconductor characteristics, which thus enabled the appearance of a dual-polarity photocurrent at two different excitation wavelengths. Furthermore, Fc and H2O2 could readily switch the photocurrent of PCOP to the cathode and anode stemming from its efficient electron collection and donation function, respectively. Based on these, a PCOP-based PEC biosensor skillfully integrating dual wavelengths with reliable accuracy and polarity switch with high sensitivity was instituted. As a result, the developed PEC biosensor exhibited a low detection limit down to 0.089 pg mL-1 for the most powerful natural carcinogen aflatoxin M1 (AFM1) assay. Impressively, the target exhibited a completely opposite photocurrent difference to the interfering substances, and the linear correlation coefficient of the assay was improved compared to single-wavelength detection. The PEC sensing platform not only provided a basis for exploring multicharacteristic photoactive material but also innovatively developed the detection mode of the PEC biosensor.

Highly efficient photocathodic cascade material for constructing sensitive photoelectrochemical biosensor.

Photocathodic biosensor possesses excellent anti-interference capability in bioanalysis, which however suffers from high electron-hole recombination rate with low photocurrent. Herein, a high-performance inorganic organic P3HT@C60@ZnO nanosphere with cascade energy band arrangement was synthesized as photoactive signal probe, which inherited the advantages of inorganic strong optical absorptivity and organic high mobility for photo-generated holes. Specifically, the well-matched band gap endowed not only the improved life for light generated carrier and promoted separation of electron-hole pairs, but also the expansion of charge-depletion layer, significantly improving the photoelectric conversion efficiency for acquiring an extremely high photocathodic signal that increased by 30 times compared with individual materials. Accordingly, by integrating with the efficient amplification of DNA nanonet derived from clamped hybrid chain reaction (C-HCR), a sensitive P3HT@C60@ZnO nanosphere based photocathodic biosensor was proposed for accurate detection of p53. The experimental results showed that the biosensor had a wide detection range from 0.1 fM to 10 nM and a low detection limit of 0.37 fM toward p53, offering a new avenue to construct sensitive PEC platform with superior anti-interference ability and hold a prospective application in early disease diagnosis and biological analysis.

Metal Porphyrin Complex Combined with Polymerization and Isomerization Cyclic Amplification for a Sensitive Photoelectrochemical Assay.

5,10,15,20-Tetrakis(4-aminophenyl)-21H,23H-porphine (TPAPP) possesses good light-harvesting ability and photoelectrochemical (PEC) cathode response signal; however, the disadvantages of easy stacking and weak hydrophilicity limit its application as a signal probe in PEC biosensors. Based on these, we prepared a Fe3+ and Cu2+ co-coordinating photoactive material (TPAPP-Fe/Cu) with horseradish peroxidase (HRP)-like activity. The metal ions in the porphyrin center not only enabled the directional flow of photogenerated electrons between electron-rich porphyrin and positive metal ions within inner-/intermolecular layers but also accelerated electron transfer through a synergistic redox reaction of Fe(III)/Fe(II) and Cu(II)/Cu(I) as well as rapid generation of superoxide anion radicals (O2-•) by mimicking catalytically produced and dissolved oxygen, thereby providing the desired cathode photoactive material with extremely high photoelectric conversion efficiency. Accordingly, by combining with toehold-mediated strand displacement (TSD)-induced single cycle and polymerization and isomerization cyclic amplification (PICA), an ultrasensitive PEC biosensor was constructed for the detection of colon cancer-related miRNA-182-5p. The ultratrace target could be converted to abundant output DNA by TSD possessing the desirable amplifying ability to trigger PICA for forming long ssDNA with repetitive sequences, thus decorating substantial TPAPP-Fe/Cu-labeled DNA signal probes for producing high PEC photocurrent. Meanwhile, the Mn(III) meso-tetraphenylporphine chloride (MnPP) was embedded in dsDNA to further exhibit a sensitization effect toward TPAPP-Fe/Cu and an acceleration effect analogous to that of metal ions in the porphyrin center above. As a result, the proposed biosensor displayed a detection limit as low as 0.2 fM, facilitating the development of high-performance biosensors and showing great potential in early clinical diagnosis.

How to improve the diagnosis of neoplastic transformation of gastric hyperplastic polyps in the context of autoimmune gastritis?: A case report and lierature review.

RATIONALE: Gastric hyperplastic polyp (GHP) commonly arises in the abnormal background mucosa, which makes it easy to be misdiagnosed and missed, and has a potential risk of malignant transformation over time. Here, we present a case of neoplastic transformation of GHP in a context of autoimmune gastritis (AIG). PATIENT CONCERNS: In 2020, a 67-year-old woman was admitted for endoscopic review 6 years after gastric polyp resection, the histological diagnosis of gastric polyp was neoplastic transformation of GHP as before. The patient had undergone multiple polypectomies at the same part. Then histological examination revealed that partial epithelial hyperplasia and dysplasia, and the neoplastic areas were interlaced with normal mucosa. DIAGNOSES AND INTERVENTIONS: We further found that the background diagnosis was AIG. These results supported the diagnosis of neoplastic transformation of GHP in a context of AIG. With the doubt of missed diagnose, we retrospectively analyzed the medical history in 2014, 2015 and 2016, confirmed the presence of AIG. Unfortunately, serological tests and special treatment were not performed. OUTCOMES: The correct diagnosis was eventually confirmed in 2020, which enables patients to receive normal treatment and monitoring, and avoids further deterioration of the disease. LESSONS: The purpose of this case report is to increase clinical awareness of neoplastic transformation of GHP in a context of AIG, and hope promise for early diagnosis and treatment.

Common materials, extraordinary behavior: An ultrasensitive and enantioselective strategy for D-Tryptophan recognition based on electrochemical Au@p-L-cysteine chiral interface.

The poly-L-cysteine modified Au nanoparticles (Au@p-L-Cys) were constructed on electrode surface as a highly efficient chiral interface for tryptophan (Trp) enantiomers recognition via one step electropolymerization. With the aid of Cu2+, L-Cys residues and D-Trp target formed a sandwich complex D-Trp-Cu2+-L-Cys, while L-Trp was unable to form such complex due to the steric hindrance provided by the chiral interface, which was confirmed by the electrochemical and SEM results. With the introduction of ferricyanide probe, D-Trp produced significant current decrease while L-Trp produced a slight current increase, which implied the successful enantioselective recognition of Trp enantiomers (specifically D-Trp) in the true sense. This novel sensor showed a surprisingly wide linear range toward D-Trp of 6 × 10-7 M to 1 × 10-2 M, with a detection limit as low as 75 nM (S/N = 3). Moreover, the exclusive enantioselectivity toward D-Trp was discovered since other amino acids showed negligible interference to detection of D-Trp. The recovery of D-Trp in human serum was between 91.30 and 109.3%, which further verified the satisfying specificity and practicality of the proposed strategy. The coordination thermodynamics by UV-Vis spectroscopy and DFT simulation were also used to investigate the enantioselective mechanism. These results highlight the great potential of using Au@p-L-Cys to construct chiral interface for enantiomers recognition and hold the promise of practical application of electrochemical chiral sensors in fields like pharmaceutics and bioanalysis.

Tyndall-Effect-inspired assay with gold nanoparticles for the colorimetric discrimination and quantification of mercury ions and glutathione.

This work initially reports a new nanosening method for simple, sensitive, specific, visual detection of mercury (II) (Hg2+) and glutathione (GSH) using the Tyndall Effect (TE) of the same colloidal gold nanoparticle (GNP) probes for efficient colorimetric signaling amplification. For the TE-inspired assay (TEA) method, arginine (Arg) molecules are pre-modified on the GNPs' surfaces (Arg-GNPs). Upon the Hg2+ introduction, it can be specifically coordinated with the terminal -NH2 and -COOH groups of the Arg molecules to make the Arg-GNPs aggregate, producing a significantly-enhanced TE signal in the reaction solution after its irradiation by a 635-nm red laser pointer pen. On the other hand, the introduction of the GSH results in the production of the original Arg-GNPs' weak TE response, as it is able to bind such metal ion via mercury-thiol reactions to inhibit the above aggregation. Under the optimal conditions, the utility of the new TEA method is well demonstrated to quantitatively detect the Hg2+ and GSH with the aid of a smartphone as a portable TE reader during the linear concentration ranges of 50-3000 and 10-3000 nM, respectively. The detection limits for the Hg2+ and GSH are estimated to be as low as ∼3.5 and ∼0.3 nM, respectively. The recovery results obtained from the detection of Hg2+ in the complex tap and pond water samples and the assay of GSH in real human serum and urine samples are also satisfactory.

Porous Fe3O4@COF-Immobilized gold nanoparticles with excellent catalytic performance for sensitive electrochemical detection of ATP.

In this work, a "signal-off" electrochemical biosensor was established for sensitive detection of adenosine triphosphate (ATP) based on Fe3O4@covalent organic framework-immobilized gold nanoparticles (Fe3O4@COF-Au NPs) porous composite material as a nanocarrier. The proposed Fe3O4@COF-Au NPs could effectively confine Au NPs in the uniform channels of the Fe3O4@COF, which successfully avoided Au NPs aggregation to a certain extent and provided a comparatively independent and stable micro-environment via its hydrophobic porous nanochannels, thereby owning excellent electro-catalytic performance for the reduction of 4-nitrophenol. Moreover, the Fe3O4@COF-Au NPs nanomaterials were served as functional platform for immobilizing DNA substrate (S0), which was used to bind with the conversion product (S1) of the target ATP for subsequent branched hybridization chain reaction (b-HCR) to form dendritic DNA strands to hinder electron transfer between Fe3O4@COF-Au NPs and 4-nitrophenol, finally achieving sensitive detection of ATP with a wide linear range of 5 pM-50 µM and a low detection limit of 1.6 pM. Such strategy provides a multifunctional immobilized platform for the sensitive detection of ATP and a versatile strategy for monitoring other biomolecules.

A core-brush 3D DNA nanostructure: the next generation of DNA nanomachine for ultrasensitive sensing and imaging of intracellular microRNA with rapid kinetics.

A highly loaded and integrated core-brush three-dimensional (3D) DNA nanostructure is constructed by programmatically assembling a locked DNA walking arm (DA) and hairpin substrate (HS) into a repetitive array along a well-designed DNA track generated by rolling circle amplification (RCA) and is applied as a 3D DNA nanomachine for rapid and sensitive intracellular microRNA (miRNA) imaging and sensing. Impressively, the homogeneous distribution of the DA and HS at a ratio of 1 : 3 on the DNA track provides a specific walking range for the DA to avoid invalid and random self-walking and notably improve the executive ability of the core-brush 3D DNA nanomachine, which easily solves the major technical challenges of traditional Au-based 3D DNA nanomachines: low loading capacity and low executive efficiency. As a proof of concept, the interaction of miRNA with the 3D DNA nanomachine could initiate the autonomous and progressive operation of the DA to cleave the HS for ultrasensitive ECL detection of target miRNA-21 with a detection limit as low as 3.57 aM and rapid imaging in living cells within 15 min. Therefore, the proposed core-brush 3D DNA nanomachine could not only provide convincing evidence for sensitive detection and rapid visual imaging of biomarkers with tiny change, but also assist researchers in investigating the formation mechanism of tumors, improving their recovery rates and reducing correlative complications. This strategy might enrich the method to design a new generation of 3D DNA nanomachine and promote the development of clinical diagnosis, targeted therapy and prognosis monitoring.

Transforming glucose into fluorescent graphene quantum dots via microwave radiation for sensitive detection of Al3+ ions based on aggregation-induced enhanced emission.

This paper initially describes a nanosensor for fluorescence detection of Al3+ ions by using graphene quantum dots (GQDs) that are synthesized via microwave-assisted single-step ring-closure condensation of glucose molecules. The one-pot synthesis strategy based on the microwave radiation could be finished in several minutes and no post-modification of the GQDs was required. In particular, the GQD nanoprobes showed a sensitive and specific fluorescence enhancement response to Al3+. The involved mechanism might be the Al3+-mediated aggregation of the GQDs leading to aggregation-induced enhanced emission (AIEE). Under optimal conditions, this new fluorescent nanosensor was able to quantitatively detect Al3+ in a linear concentration range of 0.4-500 µM. The limit of detection was estimated to be ∼59.8 nM according to the 3σ rule, which made it be among the most sensitive systems currently available for sensing the target ion. Moreover, satisfactory recovery results (ranging from 96.8 to 109.7%) of analyzing a set of real water examples additionally validated its accuracy for practical applications. Considering its simplicity, high sensitivity and specificity, low cost, and good reliability, the developed fluorescent nanosensing system for Al3+ holds great promise for broad uses in water safety, environmental monitoring, and waste management.

Highly Sensitive Photoelectrochemical Biosensor Based on Quantum Dots Sensitizing Bi2Te3 Nanosheets and DNA-Amplifying Strategies.

In this work, Bi2Te3 nanosheets treated with N-vinyl-pyrrolidinone showed highly sufficient and stable photocurrent for being used as a novel photoactive material. Accordingly, with CdTe quantum dots (QDs) sensitizing Bi2Te3 nanosheets, photoelectrochemical (PEC) biosensor coupling of DNA-amplifying strategies was constructed for sensitive miRNA-21 detection. Initially, the Bi2Te3 nanosheets on the electrode have conductive surface states with dissipationless electronic property, thus providing a highly stable photocurrent and a large surface-to-volume ratio. Then, with the participation of target miRNA-21 and auxiliary DNA, strand displacement amplification took place, thereby opening substantial DNA hairpins for triggering the next hybridization chain reaction (HCR). Through the HCR, long DNA tails decorated with CdTe QDs could thus be assembled on the electrode for enhancing the photocurrent of Bi2Te3 nanosheets. As a result, the proposed PEC biosensor showed a wide detection range from 10 fM to 100 pM with a detection limit of 3.3 fM, displaying a promising avenue to construct simple, ultrasensitive, and stable analytical techniques and tremendous potential in bioanalysis and early clinical diagnosis.

Enhanced functional DNA biosensor for distance-based read-by-eye quantification of various analytes based on starch-hydrolysis-adjusted wettability change in paper devices.

Low-cost, equipment-free and quantitative detection of a wide range of analytes of interest at home and in the field holds the potential to revolutionize disease diagnosis, environmental pollution monitoring, and food safety analysis. Herein, we describe a functional DNA biosensor for the first time that integrates analyte-directed assembly of enzyme-coated microbead probes for robust yet efficient signal amplification with a simple quantitative detection motif of distance measurement on portable paper devices based on starch-hydrolysis-adjusted wettability change of paper. Its utility is well demonstrated with highly sensitive and specific detection of model analytes ranging from adenosine (an important small biomolecule; 1.6 µM detection limit) to interferon-γ (a protein marker; 0.3 nM detection limit) and Pb2+ (a highly toxic metal ion; 0.5 nM detection limit) by simply using an inexpensive, ubiquitous ruler. The developed general method with the distance-measuring readout should be easily tailored for the portable, read-by-eye, quantitative detection of many other types of analytical targets by taking advantage of their specific functional DNA partners like aptamers and DNAzymes.

Effects of Notch Signaling Pathway in Cervical Cancer by Curcumin Mediated Photodynamic Therapy and Its Possible Mechanisms in Vitro and in Vivo.

Curcumin, as a high effect and low toxicity anti-cancer drug and photosensitiser, has synergistic and complementary effects with photodynamic therapy (PDT). However, due to its unclear mechanism, PDT's application and efficacy were limited. Notch signaling pathway, which is highly correlates with carcinogenesis and development of cervical cancer, could be a potential therapeutic targets to improve the effectiveness of PDT. Therefore, in this study, we explored the effects of Notch signaling pathway in cervical cancer by curcumin mediated PDT with/without Notch receptor blocker (DAPT), and hope to elucidate its mechanism. Firstly, the effect on the proliferation of cervical cancer Me180 cells were detected with MTT assay, and apoptosis were detected with Annexin V-FITC/PI combined with flow cytometry. Secondly, after establishment of nude mice model, dividing the experimental animals into model group, curcumin PDT group, simple DAPT group, and curcumin-PDT+DAPT group, and analyzing tumor volume changes as well as HE staining in each group. mRNA and protein expression of gene Notch-1 and its downstream NF-κB and VEGF were observed with RT-PCR, immunohistochemical staining and Western-blot with/without inhibition of Notch signaling pathway by DAPT, both in vivo and in vitro experiments. We found both DAPT and curcumin-PDT can inhibit the proliferation and induce apoptosis of cervical cancer cell. The two have synergistic effect in vitro and in vivo. This effect can effectively block the conduction of Notch signaling pathway, which is associated with down-regulation of the expression of Notch1 and NF-κB. Notch signaling pathway could be one of the targets of curcumin-PDT photodynamic therapy.

Highly-efficient luminol immobilization approach and exponential strand displacement reaction based electrochemiluminescent strategy for monitoring microRNA expression in cell.

This work used 3,4,9,10-perylenetetracarboxylic acid-luminol composite (PTCA-luminol) as signal tag with improved ECL signal and applied cruciform DNA structure mediated exponential strand displacement reaction (SDR) to construct an ultrasensitive electrochemiluminescence (ECL) biosensor for microRNA-21 (miRNA-21) detection. The novel luminol-based signal tags was synthesized utilizing the π-π stacking interaction between PTCA and luminol, realizing highly effective and stable immobilization of luminol and resulting in good stability and strong ECL response. Meanwhile, target miRNA-21 triggered disaggregation of cruciform DNA structure was used to mediate exponential SDR for target recycling amplification. Taking advantage of the novel luminol-based signal tag and exponential SDR, the proposed ECL biosensor achieved excellent sensitivity with wide linear range from 10 aM to 100 pM and detection limit was 2 aM. Moreover, this ECL biosensor was applied to estimate the expression level of miRNA-21 and pharmacodynamics of matrine in human breast cancer cells (MCF-7 cells). The proposed biosensor provided a new opportunity for the preparation of ECL nanomaterials and exhibited great application potential in other biomarkers detection, clinical application and pharmacodynamics evaluation.

Reversible and Distance-Controllable DNA Scissor: A Regenerated Electrochemiluminescence Biosensing Platform for Ultrasensitive Detection of MicroRNA.

Reversing the switching of DNA scissors with precisely control remains a compelling goal. Herein, based on strand displacement reaction within single step, the DNA scissor realized reversible switching and further controlled the distance of end strands along the movement of DNA scissor, which has been applied for the development of a regenerated sensing platform for the ultrasensitive detection of microRNA-21 (miRNA-21) with the electrochemiluminescence (ECL) complex (PEI-Ru(II)) as luminophores and diethylenetriamine (DETA) as the coreactant. In the presence of ferrocene-labeled DNA (Fc-DNA), the DETA-labeled DNA scissor clockwise switched to "off" state based on strand displacement reaction, resulting in the significant ECL quenching of Ru(II) system. Next, by using miRNA-21 as the motive fuel, the configuration of DNA scissor could be anticlockwise switched, which significantly enhanced the ECL intensity of Ru(II) complex due to the releasing of Fc-DNA and the proximity between DETA and Ru(II) complex. The reversible switching of DNA scissor led to the remarkably enhancing of ECL signal, realizing ultrasensitive detection of miRNA-21 with an excellent detection limit of 0.17 fM, which was also applied in miRNA detection successfully from different cancer cells. Impressively, the reversible switching of DNA scissor biosensor was able to realize the regeneration of the biosensing platform by adding an additional single stranded DNA (ssDNA) based on strand displacement reaction within a single step, providing a novel concept for constructing simple and sensitive regenerated biosensor.