Puerarin mitigated LPS-ATP or HG-primed endothelial cells damage and diabetes-associated cardiovascular disease via ROS-NLRP3 signalling.

The occurrence and development of diabetic vascular diseases are closely linked to inflammation-induced endothelial dysfunction. Puerarin (Pue), the primary component of Pueraria lobata, possesses potent anti-inflammatory properties. However, its vasoprotective role remains elusive. Therefore, we investigated whether Pue can effectively protect against vascular damage induced by diabetes. In the study, Pue ameliorated lipopolysaccharide-adenosine triphosphate (LPS-ATP) or HG-primed cytotoxicity and apoptosis, while inhibited reactive oxygen species (ROS)-mediated NLR family pyrin domain containing 3 (NLRP3) inflammasome in HUVECs, as evidenced by significantly decreased ROS level, NOX4, Caspase-1 activity and expression of NLRP3, GSDMD, cleaved caspase-1, IL-1ß and IL-18. Meanwhile, ROS inducer CoCI2 efficiently weakened the effects of Pue against LPS-ATP-primed pyroptosis. In addition, NLRP3 knockdown notably enhanced Pue's ability to suppress pyroptosis in LPS-ATP-primed HUVECs, whereas overexpression of NLRP3 reversed the inhibitory effects of Pue. Furthermore, Pue inhibited the expression of ROS and NLRP3 inflammasome-associated proteins on the aorta in type 2 diabetes mellitus rats. Our findings indicated that Pue might ameliorate LPS-ATP or HG-primed damage in HUVECs by inactivating the ROS-NLRP3 signalling pathway.

Enabling Uniform and Stable Lithium-Ion Diffusion at the Ultrathin Artificial Solid-Electrolyte Interface in Siloxene Anodes.

Constructing a stable and robust solid electrolyte interphase (SEI) has a decisive influence on the charge/discharge kinetics of lithium-ion batteries (LIBs), especially for silicon-based anodes which generate repeated destruction and regeneration of unstable SEI films. Herein, a facile way is proposed to fabricate an artificial SEI layer composed of lithiophilic chitosan on the surface of two-dimensional siloxene, which has aroused wide attention as an advanced anode for LIBs due to its special characteristics. The optimized chitosan-modified siloxene anode exhibits an excellent reversible cyclic stability of about 672.6 mAh g-1 at a current density of 1000 mA g-1 after 200 cycles and 139.9 mAh g-1 at 6000 mA g-1 for 1200 cycles. Further investigation shows that a stable and LiF-rich SEI film is formed and can effectively adhere to the surface during cycling, redistribute lithium-ion flux, and enable a relatively homogenous lithium-ion diffusion. This work provides constructive guidance for interface engineering strategy of nano-structured silicon anodes.

Functional annotation map of natural compounds in traditional Chinese medicines library: TCMs with myocardial protection as a case.

The chemical complexity of traditional Chinese medicines (TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform (TCMs-CFA) for large-scale predicting active compounds with potential mechanisms from TCM complex system, without isolating and activity testing every single compound one by one. The platform was established based on the integration of TCMs knowledge base, chemome profiling, and high-content imaging. It mainly included: (1) selection of herbal drugs of target based on TCMs knowledge base; (2) chemome profiling of TCMs extract library by LC‒MS; (3) cytological profiling of TCMs extract library by high-content cell-based imaging; (4) active compounds discovery by combining each mass signal and multi-parametric cell phenotypes; (5) construction of functional annotation map for predicting the potential mechanisms of lead compounds. In this stud TCMs with myocardial protection were applied as a case study, and validated for the feasibility and utility of the platform. Seven frequently used herbal drugs (Ginseng, etc.) were screened from 100,000 TCMs formulas for myocardial protection and subsequently prepared as a library of 700 extracts. By using TCMs-CFA platform, 81 lead compounds, including 10 novel bioactive ones, were quickly identified by correlating 8089 mass signals with 170,100 cytological parameters from an extract library. The TCMs-CFA platform described a new evidence-led tool for the rapid discovery process by data mining strategies, which is valuable for novel lead compounds from TCMs. All computations are done through Python and are publicly available on GitHub.

Human Carboxylesterase 1A Plays a Predominant Role in Hydrolysis of the Anti-Dyslipidemia Agent Fenofibrate in Humans.

Fenofibrate, a marketed peroxisome proliferator-activated receptor-α (PPARα) agonist, has been widely used for treating severe hypertriglyceridemia and mixed dyslipidemia. As a canonical prodrug, fenofibrate can be rapidly hydrolyzed to release the active metabolite (fenofibric acid) in vivo, but the crucial enzyme(s) responsible for fenofibrate hydrolysis and the related hydrolytic kinetics have not been well-investigated. This study aimed to assign the key organs and crucial enzymes involved in fenofibrate hydrolysis in humans, as well as reveal the impact of fenofibrate hydrolysis on its non-PPAR-mediated biologic activities. Our results demonstrated that fenofibrate could be rapidly hydrolyzed in the preparations from both human liver and lung to release fenofibric acid. Reaction phenotyping assays coupling with chemical inhibition assays showed that human carboxylesterase 1A (hCES1A) played a predominant role in fenofibrate hydrolysis in human liver and lung, while human carboxylesterase 2A (hCES2A) and human monoacylglycerol esterase (hMAGL) contributed to a very lesser extent. Kinetic analyses showed that fenofibrate could be rapidly hydrolyzed by hCES1A in human liver preparations, while the inherent clearance of hCES1A-catalyzed fenofibrate hydrolysis is much higher (>200-fold) than than that of hCES2A or hMAGL. Biologic assays demonstrated that both fenofibrate and fenofibric acid showed very closed Nrf2 agonist effects, but fenofibrate hydrolysis strongly weakens its inhibitory effects against both hCES2A and hNtoum. Collectively, our findings reveal that the liver is the major organ and hCES1A is the predominant enzyme-catalyzing fenofibrate hydrolysis in humans, while fenofibrate hydrolysis significantly reduces inhibitory effects of fenofibrate against serine hydrolases. SIGNIFICANCE STATEMENT: Fenofibrate can be completely converted to fenofibric acid in humans and subsequently exert its pharmacological effects, but the hydrolytic pathways of fenofibrate in humans have not been well-investigated. This study reported that the liver was the predominant organ and human carboxylesterase 1A was the crucial enzyme involved in fenofibrate hydrolysis in humans.

Programing Immunogenic Cell Death in Breast Tumors with Designer DNA Frameworks.

The low response rate and serious side effects of cancer treatment pose significant limitations in immunotherapy. Here, we developed a multifunctional tetrahedral DNA framework (TDF) as a drug carrier to recruit chemotherapeutants and trigger immunogenic cell death (ICD) effects, which could turn tumors from cold to hot to boost the efficacy of antitumor immunotherapy. A tumor-targeting peptide RGD was modified on the TDF to increase the delivery efficiency, and the chemotherapeutant doxorubicin (DOX) was loaded to induce ICD effects, which were assisted by the immune adjuvant of CpG immunologic sequences linked on TDF. We demonstrated that the multifunctional TDF could suppress 4T1 breast tumor growth by increasing tumor infiltration of CD8+ T cells, upregulating granzyme B and perforin expressions to twice as much as the control group, and decreasing 30% CD25+ Treg cells. Furthermore, the combination of α-PD-1 could inhibit the growth of distant tumor and suppressed tumor recurrence in a bilateral syngeneic 4T1 mouse model; the distant tumor weight inhibition rate was about 91.6%. Hence, through quantitatively targeting the delivery of DOX to reduce the side effects of chemotherapy and sensitizing the immune response by ICD effects, this multifunctional TDF therapeutic strategy displayed better treatment effect and a promising clinical application prospect.

Rationally Engineered CYP3A4 Fluorogenic Substrates for Functional Imaging Analysis and Drug-Drug Interaction Studies.

Cytochrome P450 3A4 (CYP3A4) is a key xenobiotic-metabolizing enzyme-mediated drug metabolism and drug-drug interaction (DDI). Herein, an effective strategy was used to rationally construct a practical two-photon fluorogenic substrate for hCYP3A4. Following two-round structure-based substrate discovery and optimization, we have successfully constructed a hCYP3A4 fluorogenic substrate (F8) with desirable features, including high binding affinity, rapid response, excellent isoform specificity, and low cytotoxicity. Under physiological conditions, F8 is readily metabolized by hCYP3A4 to form a brightly fluorescent product (4-OH F8) that can be easily detected by various fluorescence devices. The practicality of F8 for real-time sensing and functional imaging of hCYP3A4 has been examined in tissue preparations, living cells, and organ slices. F8 also demonstrates good performance for high-throughput screening of hCYP3A4 inhibitors and assessing DDI potentials in vivo. Collectively, this study develops an advanced molecular tool for sensing CYP3A4 activities in biological systems, which strongly facilitates CYP3A4-associated fundamental and applied research studies.

Sequencing of 19,219 exomes identifies a low-frequency variant in FKBP5 promoter predisposing to high myopia in a Han Chinese population.

High myopia (HM) is one of the leading causes of visual impairment and blindness worldwide. Here, we report a whole-exome sequencing (WES) study in 9,613 HM cases and 9,606 controls of Han Chinese ancestry to pinpoint HM-associated risk variants. Single-variant association analysis identified three newly identified -genetic loci associated with HM, including an East Asian ancestry-specific low-frequency variant (rs533280354) in FKBP5. Multi-ancestry meta-analysis with WES data of 2,696 HM cases and 7,186 controls of European ancestry from the UK Biobank discerned a newly identified European ancestry-specific rare variant in FOLH1. Functional experiments revealed a mechanism whereby a single G-to-A transition at rs533280354 disrupted the binding of transcription activator KLF15 to the promoter of FKBP5, resulting in decreased transcription of FKBP5. Furthermore, burden tests showed a significant excess of rare protein-truncating variants among HM cases involved in retinal blood vessel morphogenesis and neurotransmitter transport.

Visual Sensor Arrays for Distinction of Phenolic Acids Based on Two Single-Atom Nanozymes.

Although great achievements have been made in the study of artificial enzymes, the design of nanozymes with high catalytic activities of natural enzymes and the further establishment of sensitive biosensors still remain challenging. Here, two nanozymes, i.e., ZnCoFe three-atom nanozyme (TAzyme) and Sn single-atom nanozyme (SAzyme)/Ti3C2Tx, are developed, which show peroxidase-like catalytic activities by catalyzing the reaction of hydrogen peroxide (H2O2), 4-aminoantipyrine (4-AAP), and phenolic acids to generate colorimetric reactions. The involvement of different phenolic acids leads to the generation of different color products. These subtle color-variation profiles between these phenolic acids prompt us to exploit an electronic tongue based on the two nanozymes to distinguish phenolic acids. Data interpretation by the pattern recognition method, such as linear discriminant analysis (LDA), displays good clustering separation of six different phenolic acids at concentrations of 0.1 µM to 1 mM, validating the effectiveness of the colorimetric nanozyme sensor array.

A rationally engineered specific near-infrared fluorogenic substrate of human pancreatic lipase for functional imaging and inhibitor screening.

Obesity, now widespread all over the world, is frequently associated with several chronic diseases. Human pancreatic lipase (hPL) is a crucial digestive enzyme responsible for the digestion of dietary lipids in humans, and the inhibition of hPL is effective in reducing triglyceride intake and thus preventing and treating obesity. In this work, a practical sequential screening strategy was developed to construct a highly selective near-infrared fluorogenic substrate 7-STCFC for hPL. Under physiological conditions, 7-STCFC can be rapidly hydrolyzed by hPL to form 7-HTCFC, which triggers 254-fold NIR signal enhancement at 670 nm. 7-STCFC was successfully applied for the sensing and imaging of endogenous PL in living systems (including living cells, tissues and organs) with low cytotoxicity and high imaging resolution. Moreover, a high-throughput screening platform was established using 7-STCFC, and the inhibitory effects of 94 kinds of herbs toward hPL were evaluated. Among them, Pu-erh tea stood out with outstanding hPL inhibitory effects, and the inhibitory ingredients and involved inhibitory mechanism were further revealed, which strongly facilitates the discovery of novel anti-obesity agents targeting hPL. Collectively, these findings suggested that our strategy was practical to develop an isoform-specific fluorogenic substrate for a target enzyme, and 7-STCFC was a powerful tool for monitoring PL activity in complex biological systems with value for exploring physiological functions and rapid screening of inhibitors.

Discovery of seven-membered ring berberine analogues as highly potent and specific hCES2A inhibitors.

Human carboxylesterase 2A (hCES2A) is a key serine hydrolase responsible for the metabolic clearance of large number of compounds bearing the ester- or amide-bond(s). Inhibition of hCES2A can relieve the chemotherapy-induced toxicity and alter the pharmacokinetic bahaviors of some orally administrate esters-containing agents. However, most of the hCES2A inhibitors show poor cell-membrane permeability and poor specificity. Herein, guided by the structure activity relationships (SAR) of fifteen natural alkaloids against hCES2A, fifteen new seven-membered ring berberine analogues were designed and synthesized, and their anti-hCES2A activities were evaluated. Among all tested compounds, compound 28 showed potent anti-hCES2A effect (IC50 = 1.66 µM) and excellent selectivity over hCES1A (IC50 > 100 µM). The SAR analysis revealed that the seven-membered ring of these berberine analogues was a crucial moiety for hCES2A inhibition, while the secondary amine group of the ring-C is important for improving their specificity over other serine hydrolases. Inhibition kinetic analyses and molecular dynamic simulation demonstrated that 28 strongly inhibited hCES2A in a mixed-inhibition manner, with an estimated Ki value of 1.035 µM. Moreover, 28 could inhibit intracellular hCES2A in living HepG2 cells and exhibited suitable metabolic stability. Collectively, the SAR of seven-membered ring berberine analogues as hCES2A inhibitors were studied, while compound 28 acted as a promising candidate for developing highly selective hCES2A inhibitors.

Rational Construction of a Novel Bioluminescent Substrate for Sensing the Tumor-Associated Hydrolase Notum.

Notum, one of the key serine hydrolases in mammals, hydrolyzes the palmitoleoyl moieties of many important proteins and modulates multiple signaling pathways including Wnt/ß-catenin signaling. Notum is tightly associated with multiple human diseases, but the reliable and practical tools for sensing Notum activities in complex biological systems are rarely reported. Herein, an efficient strategy was used to rationally construct a specific bioluminescent substrate for Notum. Following computer-aided molecular design and experimental verification, octanoyl luciferin (OL) was selected as the optimum substrate for human Notum, with excellent specificity, high detection sensitivity and high signal-to-noise ratio. Under physiological conditions, OL was readily hydrolyzed by Notum or Notum-containing biological specimens to release d-luciferin that could be easily detected by various fluorescence devices in the presence of luciferase. The applicability of OL for real-time sensing native Notum was examined in living cells, extracellular matrix, and tissue preparations. OL was also used for constructing a high-throughput assay for screening of Notum inhibitors, while a natural compound (bergapten) was newly identified as a potent Notum inhibitor. Collectively, this study devises a reliable and easy-to-use tool for sensing Notum activities in biological systems, which will strongly facilitate hNotum-associated fundamental studies, disease diagnosis, and drug discovery.

Functional Imaging and Inhibitor Screening of Human Pancreatic Lipase by a Resorufin-Based Fluorescent Probe.

Human pancreatic lipase (hPL) is a crucial digestive enzyme responsible for the digestion of dietary lipids in humans, and inhibition of hPL is effective in reducing triglyceride intake, thereby preventing and treating obesity. In this study, a series of fatty acids with different carbon chain lengths were constructed to the fluorophore resorufin based on the substrate preference of hPL. Among them, RLE was found to have the best combination of stability, specificity, sensitivity and reactivity towards hPL. Under physiological conditions, RLE can be rapidly hydrolyzed by hPL and released to resorufin, which triggered approximately 100-fold fluorescence enhancement at 590 nm. RLE was successfully applied for sensing and imaging of endogenous PL in living systems with low cytotoxicity and high imaging resolution. Moreover, a visual high-throughput screening platform was established using RLE, and the inhibitory effects of hundreds of drugs and natural products toward hPL were evaluated. Collectively, this study reports a novel and highly specific enzyme-activatable fluorogenic substrate for hPL that could serve as a powerful tool for monitoring hPL activity in complex biological systems and showcases the potential to explore physiological functions and rapid screening of inhibitors.

COVID-19 Stressors and Aggression among Chinese College Students: The Mediation Role of Coping Strategies.

Although college students experienced excessive stressors (COVID-19 disease and negative COVID-19 news) during the COVID-19 pandemic, few studies have been aimed at coping strategies used by college students to deal with stress caused by the pandemic. Coping strategies are efforts to deal with anxiety in the face of a perceived threat or stress. Aggression is harmful social interaction with the intention of inflicting damage or harm upon another individual. In the present study, we aimed to examine the direct effect of stressors resulting from the pandemic on college students' aggression, as well as the indirect effect via their coping strategies. Through a cross-sectional survey of 601 Chinese college students (M-age = 20.28), we tested the proposed framework. We first found that information stressors of COVID-19 ranked highest among the four stressors of the pandemic. Results also indicated that college students' stressors of COVID-19 were directly and positively associated with their aggressive behavior. For the indirect effect, college students would adopt both adaptive coping strategies (self-help strategy) and maladaptive coping strategies (avoidance strategy and self-punishment strategy) with the stressors of COVID-19. Furthermore, adaptive coping strategy (approach strategy) was negatively related to their aggression, whereas maladaptive coping strategy (avoidance strategy and self-punishment strategy) was positively related to their aggressive behavior. The present research extends the general strain theory in the COVID-19 context. Practical implications are also discussed.

Peroxidase-Like FeCoZn Triple-Atom Catalyst-Based Electronic Tongue for Colorimetric Discrimination of Food Preservatives.

Recently, single-atom catalysts are attracting much attention in sensor field due to their remarkable peroxidase- or oxidase-like activities. Herein, peroxidase-like FeCoZn triple-atom catalyst supported on S- and N-doped carbon derived from ZIF-8 (FeCoZn-TAC/SNC) serves as a proof-of-concept nanozyme. In this paper, a dual-channel nanozyme-based colorimetric sensor array is presented for identifying seven preservatives in food. Further experiments reveal that the peroxidase-like activity of the FeCoZn TAzyme enables it to catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) and o-phenylenediamine (OPD) in the presence of H2 O2 , yielding the blue oxTMB and yellow oxOPD, respectively. However, food preservatives are adsorbed on the nanozyme surface through π-π stacking interaction and hydrogen bond, and the reduction in catalytic activity of FeCoZn TAzyme causes differential colorimetric signal variations, which provide unique "fingerprints" for each food preservative.

Improving Body Satisfaction Through Fitness App Use: Explicating the Role of Social Comparison, Social Network Size, and Gender.

Body dissatisfaction is prevalent worldwide, fueling the highly lucrative diet and plastic surgery industry, with many adverse outcomes. Yet, limited attention has been dedicated to noninvasive interventions that effectively enhance body satisfaction. We argue that, by altering the target of the social comparison process, people can shift their focus from body appearance to physical activity level. The present study investigated whether social comparison in terms of physical activity level provided by fitness apps could affect users' body satisfaction. A survey was conducted with 643 users of WeRun, the Chinese leading mobile fitness app. Subsequent analyses revealed that both upward and downward social comparison mediated the positive relationship between fitness app use and body satisfaction. Moreover, the users' social network size and gender played a moderating role in the social comparison processes. Fitness app use was positively related to downward comparison for male users; social network size moderated the relationship between fitness app use and upward comparison for female users. The utility of fitness apps in mitigating body dissatisfaction is also discussed.

Accommodation of Two-Dimensional SiOx in a Point-to-Plane Conductive Network Composed of Graphene and Nitrogen-Doped Carbon for Robust Lithium Storage.

Silicon oxides (SiOx) are one of the most promising anode materials for next-generation lithium-ion batteries owing to their abundant reserve and low lost and high reversible capacity. However, the practical application of SiOx is still hindered by their intrinsically low conductivity and huge volume change. In this regard, we design a novel anode material in which sheet-like SiOx nanosheets are encapsulated in a unique point-to-plane conductive network composed of graphene flakes and nitrogen-doped carbon spheres. This unique composite structure demonstrates high specific capacity (867.7 mAh g-1 at 0.1 A g-1), superior rate performance, and stable cycle life. The electrode delivers a superior reversible discharge capacity of 595.8 mAh g-1 after 200 cycles at 1.0 A g-1 and 287.5 mAh g-1 after 500 cycles at 5.0 A g-1. This work may shed light on the rational design of SiOx-based anode materials for next-generation high-performance lithium-ion batteries.

Inoculation works and health advocacy backfires: Building resistance to COVID-19 vaccine misinformation in a low political trust context.

This study examines the effectiveness of the inoculation strategy in countering vaccine-related misinformation among Hong Kong college students. A three-phase between-subject experiment (n = 123) was conducted to compare the persuasive effects of inoculation messages (two-sided messages forewarning about misinformation related to COVID-19 vaccines), supportive messages (conventional health advocacy), and no message control. The results show that inoculation messages were superior to supportive messages at generating resistance to misinformation, as evidenced by more positive vaccine attitudes and stronger vaccine intention. Notably, while we expected the inoculation condition would produce more resistance than the control condition, there was little evidence in favor of this prediction. Attitudinal threat and counterarguing moderated the experimental effects; issue involvement and political trust were found to directly predict vaccine attitudes and intention. The findings suggest that future interventions focus on developing preventive mechanisms to counter misinformation and spreading inoculation over the issue is an effective strategy to generate resistance to misinformation. Interventions should be cautious about using health advocacy initiated by governments among populations with low political trust.

Increasing Anticancer Activity with Phosphine Ligation in Zwitterionic Half-Sandwich Iridium(III), Rhodium(III), and Ruthenium(II) Complexes.

The synthesis and biological assessment of neutral or cationic platinum group metal-based anticancer complexes have been extremely studied, whereas there are few reports on the corresponding zwitterionic complexes. Herein, the synthesis, characterization, and bioactivity of zwitterionic half-sandwich phosphine-imine iridium(III), rhodium(III), and ruthenium(II) complexes were presented. The sulfonated phosphine-imine ligand and a group of zwitterionic half-sandwich P,N-chelating organometallic complexes were fully characterized by nuclear magnetic resonance (NMR), mass spectrum (electrospray ionization, ESI), elemental analysis, and X-ray crystallography. The solution stability of these complexes and their spectral properties were also determined. Notably, almost all of these complexes showed enhanced anticancer activity against model HeLa and A549 cancer cells than the corresponding zwitterionic pyridyl-imine N,N-chelating iridium(III) and ruthenium(II) complexes, which have exhibited inactive or low active in our previous work. The increase in the lipophilic property and intracellular uptake levels of these zwitterionic P,N-chelating complexes appeared to be associated with their superior cytotoxicity. In addition, these complexes showed biomolecular interactions with bovine serum albumin (BSA). The flow cytometry studies indicated that the representative complex Ir1 could induce early-stage apoptosis in A549 cells. Further, confocal microscopy imaging analysis displayed that Ir1 entered A549 cells through the energy-dependent pathway, targeted lysosome, and could cause lysosomal damage. In particular, these complexes could impede cell migration in A549 cells.

Study on Antidepressant Emotion Regulation Based on Feedback Analysis of Music Therapy with Brain-Computer Interface.

In today's society, people with poor mental ability are prone to neuropsychiatric diseases such as anxiety, ADHD, and depression due to long-term negative emotions. Although conventional Western medicine has certain curative effect, these drugs have significant anticholinergic side effects central toxicity as well as cardiovascular and gastrointestinal side effects which limit their application in the elderly. At present, several antidepressants used in clinic have certain limitations. According to the symptoms of depression, this paper proposes a feedback emotion regulation method of brain-computer interface music therapy. This method uses special music stimulation to regulate the release of inhibiting sex hormones in the body, reduce the influence of negative emotions on the internal environment of the body, and maintain the steady state of the body. In this method, EEG is used as the emotional control signal of depressed patients, and this biological signal is transformed into music that depressed patients can understand, so as to clarify their physiological and psychological state and realize emotional self-regulation by feedback.

Oxidase-like ZnCoFe Three-Atom Nanozyme as a Colorimetric Platform for Ascorbic Acid Sensing.

Great enthusiasm in single-atom catalysts for various catalytic reactions continues to heat up. However, the poor activity of the existing single/dual-metal-atom catalysts does not meet the actual requirement. In this scenario, the precise design of triple-metal-atom catalysts is vital but still challenging. Here, a triple-atom site catalyst of FeCoZn catalyst coordinated with S and N, which is doped in the carbon matrix (named FeCoZn-TAC/SNC), is designed. The FeCoZn catalyst can mimic the activity of oxidase by activating O2 into •O2- radicals by virtue of its atomically dispersed metal active sites. Employing this characteristic, triple-atom catalysts can become a great driving force for the development of novel biosensors featuring adequate sensitivity. First, the property of FeCoZn catalyst as an oxidase-like nanozyme was explored. The obtained FeCoZn-TAC/SNC shows remarkably enhanced catalytic performance than that of FeCoZn-TAC/NC and single/dual-atom site catalysts (FeZn, CoZn, FeCo-DAC/NC and Fe, Zn, Co-SAC/NC) because of trimetallic sites, demonstrating the synergistic effect. Further, the utility of the oxidase-like FeCoZn-TAC/SNC in biosensor field is evaluated by the colorimetric sensing of ascorbic acid. The nanozyme sensor shows a wide concentration range from 0.01 to 90 µM and an excellent detection limit of 6.24 nM. The applicability of the nanozyme sensor in biologically relevant detection was further proved in serum. The implementation of TAC in colorimetric detection holds vast promise for further development of biomedical research and clinical diagnosis.