Cooperative Signaling Research Articles

Dynamic output feedback model predictive control for polytopic uncertain systems under decode and forward cooperative relay protocol

This paper addresses the robust model predictive control (RMPC) problem for a class of polytopic uncertain systems under the decode and forward cooperative relay protocol (DFCP). In order to combat signal fading from sensors to controllers and improve communication reliability, spatial diversity is achieved through cooperative terminal relay signals. At each transmission instant, the terminal only selects a better signal for transmission and a switched system is constructed. The aim of this paper is to design a set of desired dynamic output feedback controllers in the framework of RMPC such that the switched system with the underlying DFCP is exponentially stable. By taking the influence of the randomness of DFCP derived from a three nodes model composed of DF relay, a new objective function based on the mathematical expectation of the traditional quadratic function of MPC is established. Then, the orthogonal complement technique is applied to handle the inherent couplings of variables to formulate a solvable optimisation problem. Moreover, the sufficient conditions are provided to guarantee the recursive feasibility of the MPC strategy and the stability of the established closed-loop system in terms of the average dwell time (ADT) method. Finally, three experiments are given to illustrate the effectiveness of the proposed method.

Molecular mechanism of mechanical pressure induced changes in the microenvironment of intervertebral disc degeneration.

Lower back pain, as a typical clinical symptom of spinal degenerative diseases, is emerging as a major social problem. According to recent researches, the primary cause of this problem is intervertebral disc degeneration (IVDD). IVDD is closely associated with factors such as age, genetics, mechanical stimulation (MS), and inadequate nutrition. In recent years, an increasing number of studies have further elucidated the relationship between MS and IVDD. However, the exact molecular mechanisms by which MS induces IVDD remain unclear, highlighting the need for in-depth exploration and study of the relationship between MS and IVDD. Search for relevant literature on IVDD and MS published from January 1, 2010, to the present in the PubMed database. One of the main causes of IVDD is MS, and loading modalities have an impact on the creation of matrix metalloproteinase, the metabolism of the cellular matrix, and other biochemical processes in the intervertebral disc. Nucleus pulposus cell death induced by MS, cartilage end-plate destruction accompanied by pyroptosis, apoptosis, iron death, senescence, autophagy, oxidative stress, inflammatory response, and ECM degradation interact with one another to form a cooperative signaling network. This review discusses the molecular mechanisms of the changes in the microenvironment of intervertebral discs caused by mechanical pressure, explores the interaction between mechanical pressure and IVDD, and provides new insights and approaches for the clinical prevention and treatment of IVDD.

CLlight: Enhancing representation of multi-agent reinforcement learning with contrastive learning for cooperative traffic signal control

Multi-agent reinforcement learning has shown great potential for coordinating multi-intersection traffic signals due to its powerful adaptive capabilities, treating each intersection as an agent. However, in the real world, different intersections possess differentiating characteristics such as unique vehicle distributions and traffic patterns. Most existing methods directly add neighboring intersection states to local intersections and optimize the cooperative policy network based on synthesized global features. This indirect optimization approach makes it difficult to thoroughly explore the mutual interactions among different intersection agents, preventing agents from truly learning features with cooperative awareness. To resolve these challenges, we introduce contrastive learning as representation task to the multi-intersection traffic signal control approach named CLlight for two-stage policy network updating. In the first stage, we utilize policy-based or actor-critic-based reinforcement learning methods such as A2C, SAC, and PPO to train policy networks with certain representational capabilities. In the second stage, by extracting pre- and post-masked features and reconstructing the post-masked features, the agents are encouraged to learn the similarities and differences between different intersection policies, which in turn enhances the cooperative and individual representation capabilities of the policy network. To the best of our knowledge, this is the first application of contrastive learning in the field of traffic signal control. Experimental results demonstrate, compared to other state-of-the-art traffic signal control methods, superior average travel time and average waiting time performance under various scenarios, tested on synthetic and real-world datasets.

Bifurcation and phase transitions in heterogeneous non-lane-discipline-based car-following model integrating cooperative feedback control under automated and human-driven vehicles environment

Automated vehicles (AVs) equipped with adaptive cruise control (ACC) possess different driving performances from human-driven vehicles (HDVs). AVs will have an unusual impact on the traffic flow, especially in non-lane-discipline-based (NLD) environment. Therefore, we create a heterogeneous NLD car-following model (HNLD-CFM) integrating cooperative feedback control under AVs and HDVs environment. The velocity differences between two preceding vehicles and the current vehicle are adopted for the cooperative feedback control signal. The stability condition of the HNLD-CFM is inferred through control theory, which is closely related to the proportion of AVs, lateral separation of vehicles and control signal. Moreover, bifurcation phenomena are been investigated via theory analysis and simulation. Furthermore, numerical simulation clarifies that traffic congestion can be effectively suppressed and energy consumption is reduced by increasing the proportion of AVs and lateral separation of vehicles, besides a control signal.

An Enhanced Collaborative Localization Method Based on Belief Propagation Aided by 3D Terrain Modelling

Navigation system performance degrades significantly in complex environments. It is important to analyze satellite visibility through 3D terrain modelling and separate the satellite signals propagated by NLOS to suppress the NLOS error. However, the traditional 3D terrain modelling visibility analysis method based on the pure terrain cover angle is only suitable for determining the visibility of GNSS satellites and may incorrectly separate LOS propagate measurement signals from members with low relative ranges and elevation angles under air–ground swarm conditions. To this end, this paper proposes a belief-propagating cooperative navigation method based on air–ground visibility analysis, which avoids mistakenly separating close-range LOS cooperative navigation signals by simultaneously considering the distances, elevation angles, and azimuths of the signal sources relative to the air–ground swarm members. The simulation shows that the cooperative navigation NLOS identification method based on air–ground visibility analysis proposed in this paper can more accurately realize the separation of NLOS signals under cooperative conditions than the traditional pure angular 3D terrain modelling visibility analysis method can, and the localization error of the members to be assisted is significantly reduced.

High‐Performance Cooperative DNA Nanodevice Enables Sensitive Circular RNA Imaging and Precise Tumor Growth Suppression

The utility of circular RNAs (circRNAs) as emerging biomarkers and regulatory factors in medical diagnostics and therapeutics is hampered by the challenges associated with their sensitive detection and precise modulation. Herein, a high‐performance cooperative DNA nanodevice (HCDN) based on DNA tetrahedron‐confined catalytic DNA assembly reaction (DT‐CDA) that enables both imaging and regulation of circRNAs is developed. Activation of the DT‐CDA is contingent upon the presence of the target circRNA, which, together with a replicative fuel probe, catalyzes the sequential opening of additional DT‐CDAs. This cooperative exponential signal amplification with negligible background interference allows HCDN to effectively detect minute quantities of circRNAs. Employing circSATB2 as a model, the HCDN demonstrates substantial downregulation of Cyclin D1 (CCND1) mRNA and protein levels in cellular and in vivo models, thereby inhibiting tumor growth. The innovative design of HCDN sets the stage for a powerful methodology conducive to enhanced clinical diagnostics and biomolecule manipulation, thereby advancing the capabilities and applications of DNA nanotechnology.

Integrated corridor management by cooperative traffic signal and ramp metering control

AbstractThis paper formulates a cooperative traffic control methodology that integrates traffic signal timing and ramp metering decisions into an optimization model to improve traffic operations in a corridor network. A mixed integer linear model is formulated and is solved in real time within a model predictive controller framework, where the cell transmission model is used as the system state predictor. The methodology is benchmarked in a case study corridor in San Mateo, CA, in VISSIM with two optimization scenarios, namely, optimal metering and optimal signal control, and two simulation scenarios with a preset metering plan and no metering. The numerical results show that integrated traffic signal and ramp metering control reduces delays, stops, and travel times of the corridor by up to 33.1%, 36%, and 16.4%, respectively, compared to existing benchmark conditions. With appropriate weights prioritizing freeway or arterial street operations, the integrated control balances traffic congestion between the arterial street and the freeway.

Dual-signal amplified electrochemical aptasensor based on Au/MrGO and DNA nanospheres for ultra-sensitive detection of BPA without directly modified working electrode

Rapid and sensitive analysis of bisphenol A (BPA) is essential for preventing health risks to humans and animals. Hence, a signal-amplified electrochemical aptasensor without repetitive polishing and modification of working electrode was developed for BPA using Au-decorated magnetic reduced graphene oxide (Au/MrGO)-based recognition probe (RP) and DNA nanospheres (DNS)-based signal probe (SP) cooperative signal amplification. The DNS served as a signal molecule carrier and signal amplifier, while Au/MrGO acted as a signal amplifier and excellent medium for magnetic adsorption and separation. Moreover, utilizing the excellent magnetic properties of Au/MrGO eliminates the need for repetitive polishing and multi-step direct modification of the working electrode while ensuring that all detection processes take place in solution and that used Au/MrGO can be easily recycled. The proposed aptasensor exhibited not only good stability and selectivity, but also excellent sensitivity with a limit of detection (LOD) of 8.13 fg/mL (S/N = 3). The aptasensor's practicality was proven by spiking recovery tests on actual water samples and comparing the results with those detected by HPLC. The excellent sensitivity and selectivity make this aptasensor an alternative and promising avenue for rapid detection of BPA in environmental monitoring.

CM-SLASM: A Cooperative Multitechnology Simultaneous Localization and Signal Mapping for Vehicles Indoor Positioning

CM-SLASM: A Cooperative Multitechnology Simultaneous Localization and Signal Mapping for Vehicles Indoor Positioning

Abstract 280: Aberrant β-catenin signaling from the bone marrow niche leads to transformation of IDH1/2-mutant hematopoietic stem cells and compromises response to IDH1/2 inhibitors

Abstract Our purpose is to identify stromal-derived signals required for IDH1/2-mut hematopoietic stem cells (HSCs) to become leukemogenic. Mutations in IDH genes are found in 20% of acute myeloid leukemia (AML) patients and are not transformative. They produce the oncometabolite 2HG which inhibits key epigenetic regulators. We explored whether epigenetic changes in the bone marrow (BM) niche could provide cooperative signals to IDH-mut HSCs leading to their transformation and disease development. We found that 2HG is elevated in the BM plasma of MDS/AML patients with IDH1/2 mutations as compared to IDH-wt patients. Interestingly, 2HG is taken up by BM stromal cells (BMSCs) suggesting it may induce aberrant methylation patterns in them. Indeed, methylome analysis showed hypermethylation in BMSCs of AML patients with IDH1/2 mutations compared to wt. Among the most hypermethylated genes in the IDH-mut stroma are AXIN1, AXIN2 and NDK2, all negative regulators of β-catenin; this pathway activation was previously shown to cause MDS/AML in mice and present in 38% of patients. In agreement with these findings βcat activation in the stroma of IDH-mut vs IDH-wt AML patients showed a strong positive correlation as 50% of IDH-mut patients had activated βcat in their BMSCs. Inquiring whether stroma methylation precedes HSC transformation, we analyzed samples from healthy individuals with IDH-mut clonal hematopoiesis. They exhibited increased global and AXIN1 promoter methylation compared to samples without such clones, but not active βcat in osteoblasts, indicating this might be a later step along with disease development. In fact, transplantation of HSCs from Idh2-mut mice to recipients expressing active βcat in osteoblasts led to increase in blasts and shortened survival compared to wt mice transplanted with Idh2-mut HSCs. As many patients relapse following treatment with IDH inhibitors, we investigated a potential role for βcat signaling in treatment outcome. IDH-mut AML patients who do not respond to treatment with the IDHi present more frequently with activated βcat in osteoblasts compared to responders. Analyzing samples from the same patient pre- and post-treatment with IDHi, we found before treatment most patients were positive for βcat stromal activation, whereas after treatment, all patients with complete response were negative, while patients with progressive disease remained positive. Our model suggests IDH-mut HSCs secrete 2HG inducing epigenetic alterations in the niche, some of which cause activation of the βcat pathway. In turn, this additional signal leads to the transformation of HSCs to dysplastic cells and MDS/AML development. This work uncovers a new mechanism for transformation to MDS/AML and resistance to IDHi treatment. Thus, targeting βcat activation in the stroma, in combination with IDHi, could improve treatment outcome. Citation Format: Paraskevi Vgenopoulou, Luis Flores, Ioanna Mosialou, Junfei Zhao, X. Shawn Liu, Pamela Sung, Virginie Penard-Lacronique, Martin Carroll, Stavroula Kousteni. Aberrant β-catenin signaling from the bone marrow niche leads to transformation of IDH1/2-mutant hematopoietic stem cells and compromises response to IDH1/2 inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 280.

Secrecy Enhancement of relay cooperative NOMA network based on user behavior

From the perspective of information security, relays exhibit varying levels of trustworthiness when forwarding information. For screening and eliminating the malicious users of cooperative NOMA relay networks, a reputation-based algorithm is proposed, in which the user relays (URs) are categorized into three types based on their behaviors—malicious users, speculative users, and honest users. Meanwhile, in order to minimize information leakage at the relay, cooperative interference signals are transmitted by far user (FU) and near user (NU) via the uplink while the base station (BS) is also transmitting signals to the relay. This approach increases inter-user interference (IUI) to confuse the eavesdropping capability of the relay. To verify the superiority of the proposed scheme, an asymptotic lower bound expression for the ergodic secrecy rate (ESR) of the downlink is derived to characterize the secrecy performance of the proposed scheme. Furthermore, in the case of limited system power, a joint power allocation algorithm based on the golden section method is also proposed to further enhance the security performances of the system. The simulation results validate the accuracy of the derived analysis results and demonstrate that the proposed scheme has a significant improvement in the ESR compared with the traditional scheme.

TGF-β1 induces PD-1 expression in macrophages through SMAD3/STAT3 cooperative signaling in chronic inflammation.

Programmed cell death protein 1 (PD-1), a coinhibitory T cell checkpoint, is also expressed on macrophages in pathogen- or tumor-driven chronic inflammation. Increasing evidence underscores the importance of PD-1 on macrophages for dampening immune responses. However, the mechanism governing PD-1 expression in macrophages in chronic inflammation remains largely unknown. TGF-β1 is abundant within chronic inflammatory microenvironments. Here, based on public databases, significantly positive correlations between PDCD1 and TGFB1 gene expression were observed in most human tumors. Of note, among immune infiltrates, macrophages as the predominant infiltrate expressed higher PDCD1 and TGFBR1/TGFBR2 genes. MC38 colon cancer and Schistosoma japonicum infection were used as experimental models for chronic inflammation. PD-1hi macrophages from chronic inflammatory tissues displayed an immunoregulatory pattern and expressed a higher level of TGF-β receptors. Either TGF-β1-neutralizing antibody administration or macrophage-specific Tgfbr1 knockdown largely reduced PD-1 expression on macrophages in animal models. We further demonstrated that TGF-β1 directly induced PD-1 expression on macrophages. Mechanistically, TGF-β1-induced PD-1 expression on macrophages was dependent on SMAD3 and STAT3, which formed a complex at the Pdcd1 promoter. Collectively, our study shows that macrophages adapt to chronic inflammation through TGF-β1-triggered cooperative SMAD3/STAT3 signaling that induces PD-1 expression and modulates macrophage function.

G-quadruplex-regulated exonuclease cooperative hydrolysis signal transduction strategy for processing molecular temporal information

Based on the enzyme-resistant properties of G-quadruplexes, combined with Exo III and Exo λ, a G-quadruplex-regulated exonuclease cooperative hydrolysis signal transduction strategy is proposed and applied to processing molecular temporal information.

Abstract C053: Multi-omics guided design of lymphoid organoids to study cooperative cell signaling in lymphomas

Abstract Our collaborative research (Cell1) used 1001 patients of diffuse large B-cell lymphoma (DLBCL) to show that genetic alterations interact with clinical factors to impact overall survival (OS) in DLBCL. B cell receptor (BCR) signaling-driven activated B cell-like (ABC) DLBCL subtypes is the most chemo-resistant subtype to the frontline therapy R-CHOP, with 40% of patients experiencing no response or relapse. We have systematically examined disparities in lymphoma outcomes and identified African-American (AA) patients as a poor-risk population in DLBCL, with a diagnosis age 10 years younger than other racial groups. We found that AA-DLBCL patients experienced inferior 5-year OS compared to non-Hispanic whites (38% vs 46%)2,3. We performed the first-ever characterization of genetic alterations among AA-DLBCL patients and demonstrated distinct mutation patterns across DLBCL arising in AA ancestry groups4. While some of the most frequent genetic mutations in AA-DLBCL are related to chromatin and epigenetics, few studies have investigated racial disparities in patients with aggressive ABC DLBCLs. The mechanisms that determine this racial inequality are unknown but may lie in the particular spectrum of mutations that act in concert with intricate survival signals imparted by the lymph node tumor microenvironment (Ly-TME). The pathogenesis of ABC DLBCLs has been linked to constitutive activation of and cooperation between the BCR and Toll-like receptor (TLR) pathways. These pathways are emerging as novel therapeutic targets, with a particular interest in MALT1 (mucosa-associated lymphoid tissue translocation protein 1). However, the genetic heterogeneity of ABC DLBCLs and the cooperative signaling mediated by the Ly-TME have led to discrepancies in drug responses. As a first step towards understanding Ly-TME in DLBCLs (Nature Materials5), we used DLBCL patient samples from multiple cohorts, covering >1100 samples and imaging analysis to determine immune and ECM cues in the lymphoid TME. These samples were not classified into racial categories. We designed a biomaterials-based modular lymphoma organoid that presents specific integrin ligands at controlled densities to DLBCLs. Human ABC-DLBCLs responded to MALT1 inhibition in an integrin-ligand-dependent manner. TLR activation with TLR agonists rescued cells from MALT1 inhibitors, possibly due to increased MALT1 expression. The inclusion of T-cell signals increased MALT1 expression and rescued cells from MALT1 inhibitor-mediated killing in cell lines and human PDX organoids. Changes in RNA-seq and phosphorylation in the TLR & BCR pathways were used to inform effective combination therapy approaches with MALT1 inhibitors in vitro and in vivo5. Ongoing work is determining the racial disparities in AA lymphomas through complex interactions between Ly-TME and DLBCLs.

Enhancement of cooperation induced by information-payoff evolution on two-layer complex networks

Human behavior will be influenced by information. Thus, we propose a model of interdependent scale-free networks to depict this situation. One layer represents the information network with cooperative and defective signals, and the other one indicates the game network with node-type and link-type players. Within this model, the nodes of the information network and the game network correspond one by one, but the types of signals and strategies, as well as the edges of the two networks, need not to be strictly consistent. Furthermore, signals in the information network are constantly updated in the unique way, which can influence dissemination of behavior in the game network. Herein, we investigate the impact of signal update probability and the proportion of link-type players on the evolution of cooperation. Lots of simulation results indicate that such simple setup can greatly facilitate the evolution of cooperation.

BannMI deciphers potential n-to-1 information transduction in signaling pathways to unravel message of intrinsic apoptosis.

Cell fate decisions, such as apoptosis or proliferation, are communicated via signaling pathways. The pathways are heavily intertwined and often consist of sequential interaction of proteins (kinases). Information integration takes place on the protein level via n-to-1 interactions. A state-of-the-art procedure to quantify information flow (edges) between signaling proteins (nodes) is network inference. However, edge weight calculation typically refers to 1-to-1 interactions only and relies on mean protein phosphorylation levels instead of single cell distributions. Information theoretic measures such as the mutual information (MI) have the potential to overcome these shortcomings but are still rarely used. This work proposes a Bayesian nearest neighbor-based MI estimator (BannMI) to quantify n-to-1 kinase dependency in signaling pathways. BannMI outperforms the state-of-the-art MI estimator on protein-like data in terms of mean squared error and Pearson correlation. Using BannMI, we analyze apoptotic signaling in phosphoproteomic cancerous and noncancerous breast cell line data. Our work provides evidence for cooperative signaling of several kinases in programmed cell death and identifies a potential key role of the mitogen-activated protein kinase p38. Source code and applications are available at: https://github.com/zuiop11/nn_info and can be downloaded via Pip as Python package: nn-info.

Music production and its role in coalition signaling during foraging contexts in a hunter-gatherer society.

Music is a cultural activity universally present in all human societies. Several hypotheses have been formulated to understand the possible origins of music and the reasons for its emergence. Here, we test two hypotheses: (1) the coalition signaling hypothesis which posits that music could have emerged as a tool to signal cooperative intent and signal strength of alliances and (2) music as a strategy to deter potential predators. In addition, we further explore the link between tactile cues and the propensity of mothers to sing toward infants. For this, we investigated the singing behaviors of hunter-gatherer mothers during daily foraging trips among the Mbendjele BaYaka in the Republic of the Congo. Although singing is a significant component of their daily activities, such as when walking in the forest or collecting food sources, studies on human music production in hunter-gatherer societies are mostly conducted during their ritual ceremonies. In this study, we collected foraging and singing behavioral data of mothers by using focal follows of five BaYaka women during their foraging trips in the forest. In accordance with our predictions for the coalition signaling hypothesis, women were more likely to sing when present in large groups, especially when group members were less familiar. However, predictions of the predation deterrence hypothesis were not supported as the interaction between group size and distance from the village did not have a significant effect on the likelihood of singing. The latter may be due to limited variation in predation risk in the foraging areas, because of the intense bush meat trade, and hence, future studies should include foraging areas with higher densities of wild animals. Lastly, we found that mothers were more likely to sing when they were carrying infants compared to when infants were close, but carried by others, supporting the prediction that touch plays an important prerequisite role in musical interaction between the mother and child. Our study provides important insight into the role of music as a tool in displaying the intent between or within groups to strengthen potentially conflict-free alliances during joint foraging activities.

Asymmetric heterogeneities and the role of transfers in a public goods experiment

Previous experimental research has shown that cooperation is especially challenging in situations involving heterogeneous actors. Here, we investigate the effect of allowing unconditional transfers in a public goods game when actors differ asymmetrically in their endowments and productivity levels. Under this setup, full efficiency, in terms of highest maximum group payoff, can only be achieved with the full transfer of resources from the players with high endowment and low productivity to the players with high productivity but low endowment. We show that, in this setting, the availability of transfers enhances public good provision and cooperation. The voluntary transfer serves as a powerful cooperative signal, leading to high contribution rates among the recipients. However, if the transfer possibility is given but not used, cooperation erodes.

Ribosome biosynthesis and Hedgehog activity are cooperative actionable signaling mechanisms in breast cancer following radiotherapy

Hyperactivated ribosome biosynthesis is attributed to a need for elevated protein synthesis that accommodates cell growth and division, and is characterized by nucleomorphometric alterations and increased nucleolar counts. Ribosome biogenesis is challenged when DNA-damaging treatments such as radiotherapy are utilized. Tumor cells that survive radiotherapy form the basis of recurrence, tumor progression, and metastasis. In order to survive and become metabolically revitalized, tumor cells need to reactivate RNA Polymerase I (RNA Pol I) to synthesize ribosomal RNA, an integral component of ribosomes. In this study, we showed that following radiation therapy, tumor cells from breast cancer patients demonstrate activation of a ribosome biosynthesis signature concurrent with enrichment of a signature of Hedgehog (Hh) activity. We hypothesized that GLI1 activates RNA Pol I in response to irradiation and licenses the emergence of a radioresistant tumor population. Our work establishes a novel role for GLI1 in orchestrating RNA Pol I activity in irradiated breast cancer cells. Furthermore, we present evidence that in these irradiated tumor cells, Treacle ribosome biogenesis factor 1 (TCOF1), a nucleolar protein that is important in ribosome biogenesis, facilitates nucleolar translocation of GLI1. Inhibiting Hh activity and RNA Pol I activity disabled the outgrowth of breast cancer cells in the lungs. As such, ribosome biosynthesis and Hh activity present as actionable signaling mechanisms to enhance the effectiveness of radiotherapy.

A triple amplification strategy using GR-5 DNAzyme as a signal medium for ultrasensitive detection of trace Pb2+ based on CRISPR/Cas12a empowered electrochemical biosensor

Lead ions (Pb2+) are a well-known toxic heavy metal that poses a significant threat to human health. Therefore, the development of a simple and ultrasensitive technique for detecting Pb2+ is essential. With their trans-cleavage properties, the newly discovered CRISPR-V effectors have become a potential high-precision biometric tool. In this regard, a CRISPR/Cas12a-based electrochemical biosensor (E-CRISPR) has been developed, which is combined with the GR-5 DNAzyme that can specifically recognize Pb2+. In this strategy, the GR-5 DNAzyme acts as a signal-mediated intermediary, which can convert Pb2+ into nucleic acid signals, thereby becoming single-stranded DNA that triggers strand displacement amplification (SDA) reaction. This is coupled with following activated CRISPR/Cas12a cleavage of the electrochemical signal probe, enabling cooperative signal amplification for ultrasensitive Pb2+ detection. The proposed method has a detection limit as low as 0.02 pM. Therefore, we have developed an E-CRISPR detection platform with GR-5 DNAzyme as a signal medium (called SM-E-CRISPR biosensor). This provides a method for the CRISPR system to specifically detect non-nucleic substances by converting the signal using a medium.