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.

Absorption, distribution, metabolism and excretion of linaprazan glurate in rats.

Linaprazan (AZD0865, TX07) is one of potassium-competitive acid blockers. However, linaprazan is rapidly excreted from the body, shortening its acid inhibition property. Linaprazan glurate (X842) is a prodrug of linaprazan with a prolonged inhibitory effect on gastric acid secretion. Linaprazan glurate has entered clinical trials, but few studies have reported its metabolism in non-clinical and clinical settings. In this study, we studied the pharmacokinetics, tissue distribution, mass balance, and metabolism of linaprazan glurate in rats after a single oral dose of 2.4 mg/kg (100 µCi/kg) [14C]linaprazan glurate. The results demonstrated that linaprazan glurate was mainly excreted via feces in rats with 70.48% of the dose over 168 h. The plasma AUC0-∞ of linaprazan glurate in female rats was 2 times higher than that in male rats. Drug-related substances were mainly concentrated in the stomach, eyes, liver, small intestine, and large intestine after administration. In blood, drug-related substances were mostly distributed into plasma instead of hemocytes. In total, 13 metabolites were detected in rat plasma, urine, feces, and bile. M150 (2,6-dimethylbenzoic acid) was the predominant metabolite in plasma, accounting for 80.65% and 67.65% of AUC0-24h in male and female rats, respectively. Based on the structures, linaprazan glurate was mainly hydrolyzed into linaprazan, followed by a series of oxidation, dehydrogenation, and glucuronidation in rats. Besides, CES2 is the main metabolic enzyme involved in the hydrolysis of linaprazan glurate to linaprazan.

Simple, sensitive, colorimetric detection of pyrophosphate via the analyte-triggered decomposition of metal-organic frameworks regulating their adaptive multi-color Tyndall effect.

This paper describes initially the application of the Tyndall effect (TE) of metal-organic framework (MOF) materials as a colorimetric signaling strategy for the sensitive detection of pyrophosphate ion (PPi). The used MOF NH2-MIL-101(Fe) was prepared with Fe3+ ions and fluorescent ligands of 2-amino terephthalic acid (NH2-BDC). The fluorescence of NH2-BDC in MOF is quenched due to the ligand-to-metal charge transfer effect, while the NH2-MIL-101(Fe) suspension shows a strong TE. In the presence of PPi analyte, the MOFs will undergo decomposition because of the competitive binding of Fe3+ by PPi over NH2-BDC, resulting in a significant decrease in the TE signal and fluorescence restoration from the released ligands. The results demonstrate that the new method only requires a laser pointer pen (for TE creation) and a smartphone (for portable quantitative readout) to detect PPi in a linear concentration range of 1.25-800 µM, with a detection limit of ~210 nM (3σ) which is ~38 times lower than that obtained from traditional fluorescence with a spectrophotometer (linear concentration range, 50-800 µM; detection limit, 8.15 µM). Moreover, the acceptable recovery of PPi in several real samples (i.e., pond water, black tea, and human serum and urine) ranges from 97.66 to 119.15%.

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.

Deciphering the Mechanisms of Photo-Enhanced Catalytic Activities in Plasmonic Pd-Au Heteromeric Nanozymes for Colorimetric Analysis.

The growing demand for highly active nanozymes in various fields has led to the development of several strategies to enhance their activity. Plasmonic enhancement, a strategy used in heterogenous catalysis, represents a promising strategy to boost the activity of nanozymes. Herein, Pd-Au heteromeric nanoparticles (Pd-Au dimers) with well-defined heterointerfaces have been explored as plasmonic nanozymes. As a model system, the Pd-Au dimers with integrated peroxidase (POD)-like activity and plasmonic activity are used to investigate the effect of plasmons on enhancing the activity of nanozymes under visible light irradiation. Mechanistic studies revealed that the generation of hot electron-hole pairs plays a dominant role in plasmonic effect, and it greatly enhances the decomposition of H2 O2 to the reactive oxygen species (ROS) intermediates (•OH, •O2 - and 1 O2 ), leading to elevated POD-like activity of the Pd-Au dimers. Finally, the Pd-Au dimers are applied in the plasmon-enhanced colorimetric method for the detection of alkaline phosphatase, exhibiting broad linear range and low detection limit. This study not only provides a straightforward approach for regulating nanozyme activity through plasmonic heterostructures but also sheds light on the mechanism of plasmon-enhanced catalysis of nanozymes.

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.

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.

Boosting plasmon-enhanced electrochemistry by in situ surface cleaning of plasmonic nanocatalysts.

The application of surface plasmons in heterogeneous catalysis has attracted widespread attention due to their promising potential for harvesting solar energy. The effect of surface adsorbates on catalysts has been well documented in many traditional reactions; nonetheless, their role in plasmonic catalysis has been rarely studied. In this study, an in situ electrochemical surface cleaning strategy is developed and the influence of surface adsorbates on plasmon-enhanced electrochemistry is investigated. Taking Au nanocubes as an example, plasmonic catalysts with clean surfaces are obtained by Cu2O coating and in situ electrochemical etching. During this process, the surface adsorbates of Au nanocubes are removed together with the Cu2O shells. The Au nanocubes with clean surfaces exhibit remarkable performance in plasmon-enhanced electrooxidation of glucose and an enhancement of 445% is demonstrated. The Au NCs with clean surfaces can not only provide more active sites but also avoid halides as hole scavengers, and therefore, the efficient utilization of hot holes by plasmonic excitation is achieved. This process is also generalized to other molecules and applied in electrochemical sensing with high sensitivity. These results highlight the critical role of surface adsorbates in plasmonic catalysis and may forward the design of efficient plasmonic catalysts for plasmon-enhanced electrochemistry.

Colorimetric and fluorescence dual-mode pH sensor based on nitrogen-doped carbon dots and its diverse applications.

A dual-mode pH sensor based on nitrogen-doped carbon dots (N-CDs) with the source of o-phenylenediamine and tryptophan has been constructed. Under the stimulation of pH, the N-CDs exhibited prominent both color and fluorescence changes, leading to the rarely discovered colorimetric and fluorescent dual-readouts for the evaluation of pH. The mathematic relationship was established between pH and fluorescence intensity of N-CDs, and between pH and the UV-Vis absorbance ratio at 630 nm and 488 nm of N-CDs, respectively, over a quite broad pH range of 2.2 to 12.0. Multiple techniques are used to explore the dual-mode pH-responsive mechanism, and the preliminary explanation is put forward. The experimental results show that the N-CDs have visualized pH sensing applicability for actual samples, including various water samples and HeLa cell. Furthermore, the N-CD ink is developed for successful information encryption and anti-counterfeiting. This work might provide valuable insights into the sensing mechanism of CDs, and the application potential of CDs in broader fields.

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.

Photoactive conjugated microporous polymer@C60 with quencher on tailed Y-triangular DNA structure for high-performance signal-off photoelectrochemical biosensing.

Herein, we synthesized a conjugated microporous polymer (CMP) decorated C60 (CMP@C60) with high photoelectric conversion efficiency, in which continuously repeated donor-acceptor (D-A) π electron unit within one molecule of CMP on C60 could not only effectively increase the mobility of photogenerated carriers with improved electron transmission, but also constitute the cascade energy band matching with reduced electron-hole recombination. Based on the high-performance of CMP@C60 for producing exciting initial photoelectrochemical (PEC) signal, a sensitive signal-off sensing platform was designed for lead ion (Pb2+) assay by coupling with quencher methylene blue (MB) interacting on efficient long tailed Y-triangular DNA structure (LYTD). The proposed LYTD with a tripod structure could generate six long tails in situ on its side at the same time via a simple hybridization chain reaction (HCR), providing notably grooves on electrode to accommodate quencher MB to significantly depress the signal for sensitive detection of Pb2+. As a result, the proposed PEC biosensor revealed excellent analysis capability with a low detection limit of 0.3 fM (S/N = 3). Additionally, it also showed satisfactory stability in the detection of tap water samples, lake water samples and clinical serum samples, manifesting great application prospect in the areas of environmental pollutant detection.

Development of Levo-Lansoprazole Chiral Molecularly Imprinted Polymer Sensor Based on the Polylysine-Phenylalanine Complex Framework Conformational Separation.

The efficacies and toxicities of chiral drug enantiomers are often dissimilar, necessitating chiral recognition methods. Herein, a polylysine-phenylalanine complex framework was used to prepare molecularly imprinted polymers (MIPs) as sensors with enhanced specific recognition capabilities for levo-lansoprazole. The properties of the MIP sensor were investigated using Fourier-transform infrared spectroscopy and electrochemical methods. The optimal sensor performance was achieved by applying self-assembly times of 30.0 and 25.0 min for the complex framework and levo-lansoprazole, respectively, eight electropolymerization cycles with o-phenylenediamine as the functional monomer, an elution time of 5.0 min using an ethanol/acetic acid/H2O mixture (2/3/8, V/V/V) as the eluent, and a rebound time of 10.0 min. A linear relationship was observed between the sensor response intensity (ΔI) and logarithm of the levo-lansoprazole concentration (l-g C) in the range of 1.0 × 10-13-3.0 × 10-11 mol/L. Compared with a conventional MIP sensor, the proposed sensor showed more efficient enantiomeric recognition, with high selectivity and specificity for levo-lansoprazole. The sensor was successfully applied to levo-lansoprazole detection in enteric-coated lansoprazole tablets, thus demonstrating its suitability for practical applications.

Electrochemical biomimetic enzyme cascade amplification combined with target-induced DNA walker for detection of thrombin.

Fe-N-doped carbon nanomaterials (Fe-N/CMs) were designed as a novel biomimetic enzyme with excellent peroxidase-like activity to achieve high-efficient enzyme cascade catalytic amplification with the aid of glucose oxidase (GOx), which was further combined with target-induced DNA walker amplification to develop a sensitive electrochemical biosensor for thrombin detection. Impressively, massive output DNA was transformed from small amounts of target thrombin by highly effective DNA walker amplification as protein-converting strategy, which could then induce the immobilization of functionalized nanozyme on the electrode surface to achieve the high-efficient electrochemical biomimetic enzyme cascade amplification. As a result, an amplified enzyme cascade catalytic signal was measured for thrombin detection ranging from 0.01 pM to 1 nM with a low detection limit of 3 fM. Importantly, the new biomimetic enzyme cascade reaction coupled the advantages of natural enzyme and nanozyme, which paved an avenue to construct varied artificial multienzymes amplification systems for biosensing, bioanalysis, and disease diagnosis applications.

Quantitative colorimetric sensing of heavy metal ions via analyte-promoted growth of Au nanoparticles with timer or smartphone readout.

This work describes two new colorimetric nanosensors for label-free, equipment-free quantitative detection of nanomolar copper (II) (Cu2+) and mercury (II) (Hg2+) ions. Both are based on the analyte-promoted growth of Au nanoparticles (AuNPs) from the reduction of chloroauric acid by 4-morpholineethanesulfonic acid. For the Cu2+ nanosensor, the analyte can accelerate such a redox system to rapidly form a red solution containing dispersed, uniform, spherical AuNPs that is related to these particles' surface plasmon resonance property. For the Hg2+ nanosensor, on the other hand, a blue mixture consisting of aggregated, ill-defined AuNPs with various sizes can be created, showing a significantly enhanced Tyndall effect (TE) signal (in comparison with that produced in the red solution of AuNPs). By using a timer and a smartphone to quantitatively measure the time of producing the red solution and the TE intensity (i.e., the average gray value of the corresponding image) of the blue mixture, respectively, the developed nanosensors are well demonstrated to achieve linear ranges of 6.4 nM to 100 µM and 6.1 nM to 1.56 µM for Cu2+ and Hg2+, respectively, with detection limits down to 3.5 and 0.1 nM, respectively. The acceptable recovery results obtained from the analysis of the two analytes in the complex real water samples including drinking water, tap water, and pond water ranged from 90.43 to 111.56%.

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.

Dual-sensitized heterojunction PDA/ZnO@MoS2 QDs combined with multilocus domino-like DNA cascade reaction for ultrasensitive photoelectrochemical biosensor.

In this work, by integrating with a highly efficient multilocus domino-like cascade reaction on DNA nanonet, an ultrasensitive PEC biosensor based on dual-sensitized PDA/ZnO@MoS2 QDs photoactive material as signal probe was proposed for detection of miRNA-182-5p. The dual-sensitized PDA/ZnO@MoS2 QD composed by both of p-n and S-scheme heterojunctions on electrode generated an extremely high initial PEC signal, which however quenched by CdTe QDs decorated on DNA nanonet owing to the significant p-n quenching effect. Thereafter, the output DNA (RS) from DSN enzyme-assisted target recycling amplification triggered an ingenious multilocus domino-like DNA cascade reaction on DNA nanonet for releasing numerous CdTe QDs. Thanks to the multilocus domino-like mode that owned abundant binding sites for increasing trigger efficiency and drove cascade reaction automatically advance along four stated pathways, the target conversion rate could be improved effectively compared with that of traditional approaches, significantly enhancing the detection sensitivity. Consequently, the developed PEC biosensor exhibited a low detection limit to 0.17 fM, providing a new avenue for sensitive, fast and reliable sensing of various DNA/RNA.

Au nano-flower/organic polymer heterojunction-based cathode photochemical biosensor with reduction-accelerated quenching effect of porphyrin manganese.

In this work, a novel reduction-accelerated quenching of manganese porphyrin (MnPP) based signal-off cathode photochemical (PEC) biosensor by using Au nano-flower/organic polymer (PTB7-Th) heterojunction as platform was proposed for ultrasensitive detection of Hg2+. Firstly, the photoactive PTB7-Th with Au nano-flower on electrode could form a typical Mott-Schottky heterojunction for acquiring an extremely high cathode signal. Meanwhile, the presence of target Hg2+ could bring in the formation of T-Hg2+-T based scissor-like DNA walker, which thus activated efficient Mg2+-specific DNAzyme based cleavage recycling to shear hairpin H2 on electrode to exposure abundant trigger sites of hybridization chain reaction (HCR) for in-situ decoration of quencher MnPP. Here, besides the steric hinderance and light competition effect of MnPP decorated DNA nanowires attributing to signal decrease, we for the first time testified the MnPP reduction-accelerated quenching that constantly consumed the photo-generated electron by using cyclic voltammetry (CV). As a result, the proposed biosensor had excellent sensitivity and selectivity to Hg2+ in the range of 1 fM-10 nM with a detection limit of 0.48 fM. The actual sample analysis showed that the biosensor could reliably and quantitatively identify Hg2+, indicating an excellent application prospect in routine detection.