New electrophiles targeting thiols in a reversible covalent manner.

Reversible covalent electrophiles with the advantages of both reversible and covalent interactions receive much attention in the fields of chemical biology and medicinal chemistry. Here, we report two electron-deficient olefins activated by amide and ester, amide-substituted acrylamide and methyl ester-substituted acrylamide, targeting thiols in a reversible covalent manner.

Robo-Matter towards reconfigurable multifunctional smart materials.

Maximizing materials utilization efficiency via enhancing their reconfigurability and multifunctionality offers a promising avenue in addressing the global challenges in sustainability. To this end, significant efforts have been made in developing reconfigurable multifunctional smart materials, which can exhibit remarkable behaviors such as morphing and self-healing. However, the difficulty in efficiently manipulating and controlling matter at the building block level with manageable cost and complexity, which is crucial to achieving superior responsiveness to environmental clues and stimuli, has significantly hindered the further development of such smart materials. Here we introduce a concept of Robo-Matter, which can be activated and controlled through external information exchange at the building block level, to enable a high-level of controllability, mutability and versatility for reconfigurable multifunctional smart materials. Using specially designed micro-robot building blocks with symmetry-breaking active motion modes, tunable anisotropic interactions, and interactive coupling with a programmable spatial-temporal dynamic light field, we demonstrate an emergent Robot-Matter duality, which enables a spectrum of desirable behaviors spanning from matter-like properties such as ultra-fast self-assembly and adaptivity, to robot-like properties including active force output, smart healing, smart morphing and infiltration. Our work demonstrates a promising direction for designing next-generation smart materials and large-scale robotic swarms.

Mechanistic insights into Fe3O4-mediated inhibition of H2S gas production in sludge anaerobic digestion.

The addition of iron-based conductive materials has been extensively validated as a highly effective approach to augment methane generation from anaerobic digestion (AD) process. In this work, it was additionally discovered that Fe3O4 notably suppressed the production of hazardous H2S gas during sludge AD. As the addition of Fe3O4 increased from 0 to 20 g/L, the accumulative H2S yields decreased by 89.2 % while the content of element sulfur and acid volatile sulfide (AVS) respectively increased by 55.0 % and 30.4 %. Mechanism analyses showed that the added Fe3O4 facilitated sludge conductive capacity, and boosted the efficiency of extracellular electron transfer, which accelerated the bioprocess of sulfide oxidation. Although Fe3O4 can chemically oxidize sulfide to elemental sulfur, microbial oxidation plays a major role in reducing H2S accumulation. Moreover, the released iron ions reacted with soluble sulfide, which promoted the chemical equilibrium of sulfide species from H2S to metal sulfide. Microbial analysis showed that some SRBs (i.e., Desulfomicrobium and Defluviicoccus) and SOB (i.e., Sulfuritalea) changed into keystone taxa (i.e., connectors and module hubs) in the reactor with Fe3O4 addition, showing that the functions of sulfate reduction and sulfur oxidation may play important roles in Fe3O4-present system. Fe3O4 presence also increased the content of functional genes encoding sulfide quinone reductase and flavocytochrome c sulfidedehydrogenase (e.g., Sqr and Fcc) that could oxidize sulfide to sulfur. The impact of other iron-based conductive material (i.e., zero-valent iron) was also verified, and the results showed that it could also significantly reduce H2S production. These findings provide new insights into the effect of iron-based conductive materials on anaerobic process, especially sulfur conversion.

How Does Triclocarban Affect Sulfur Transformation in Anaerobic Systems?

Triclocarban (TCC), as a typical antimicrobial agent, accumulates at substantial levels in natural environments and engineered systems. This work investigated the impact of TCC on anaerobic sulfur transformation, especially toxic H2S production. Experimental findings revealed that TCC facilitated sulfur flow from the sludge solid phase to liquid phase, promoted sulfate reduction and sulfur-containing amino acid degradation, and largely improved anaerobic H2S production, i.e., 50-600 mg/kg total suspended solids (TSS) TCC increased the cumulative H2S yields by 24.76-478.12%. Although TCC can be partially biodegraded in anaerobic systems, the increase in H2S production can be mainly attributed to the effect of TCC rather than its degradation products. TCC was spontaneously adsorbed by protein-like substances contained in microbe extracellular polymers (EPSs), and the adsorbed TCC increased the direct electron transfer ability of EPSs, possibly due to the increase in the content of electroactive polymer protein in EPSs, the polarization of the amide group C═O bond, and the increase of the α-helical peptide dipole moment, which might be one important reason for promoting sulfur bioconversion processes. Microbial analysis showed that the presence of TCC enriched the organic substrate-degrading bacteria and sulfate-reducing bacteria and increased the abundances of functional genes encoding sulfate transport and dissimilatory sulfate reduction.

RLI-SLAM: Fast Robust Ranging-LiDAR-Inertial Tightly-Coupled Localization and Mapping.

Simultaneous localization and mapping (SLAM) is an essential component for smart robot operations in unknown confined spaces such as indoors, tunnels and underground. This paper proposes a novel tightly-coupled ranging-LiDAR-inertial simultaneous localization and mapping framework, namely RLI-SLAM, which is designed to be high-accuracy, fast and robust in the long-term fast-motion scenario, and features two key innovations. The first one is tightly fusing the ultra-wideband (UWB) ranging and the inertial sensor to prevent the initial bias and long-term drift of the inertial sensor so that the point cloud distortion of the fast-moving LiDAR can be effectively compensated in real-time. This enables high-accuracy and robust state estimation in the long-term fast-motion scenario, even with a single ranging measurement. The second one is deploying an efficient loop closure detection module by using an incremental smoothing factor graph approach, which seamlessly integrates into the RLI-SLAM system, and enables high-precision mapping in a challenging environment. Extensive benchmark comparisons validate the superior accuracy of the proposed new state estimation and mapping framework over other state-of-the-art systems at a low computational complexity, even with a single ranging measurement and/or in a challenging environment.

PerturbDB for unraveling gene functions and regulatory networks.

Perturb-Seq combines CRISPR (clustered regularly interspaced short palindromic repeats)-based genetic screens with single-cell RNA sequencing readouts for high-content phenotypic screens. Despite the rapid accumulation of Perturb-Seq datasets, there remains a lack of a user-friendly platform for their efficient reuse. Here, we developed PerturbDB (http://research.gzsys.org.cn/perturbdb), a platform to help users unveil gene functions using Perturb-Seq datasets. PerturbDB hosts 66 Perturb-Seq datasets, which encompass 4 518 521 single-cell transcriptomes derived from the knockdown of 10 194 genes across 19 different cell lines. All datasets were uniformly processed using the Mixscape algorithm. Genes were clustered by their perturbed transcriptomic phenotypes derived from Perturb-Seq data, resulting in 421 gene clusters, 157 of which were stable across different cellular contexts. Through integrating chemically perturbed transcriptomes with Perturb-Seq data, we identified 552 potential inhibitors targeting 1409 genes, including an mammalian target of rapamycin (mTOR) signaling inhibitor, retinol, which was experimentally verified. Moreover, we developed a 'Cancer' module to facilitate the understanding of the regulatory role of genes in cancer using Perturb-Seq data. An interactive web interface has also been developed, enabling users to visualize, analyze and download all the comprehensive datasets available in PerturbDB. PerturbDB will greatly drive gene functional studies and enhance our understanding of the regulatory roles of genes in diseases such as cancer.

Small Molecule-Induced Post-Translational Acetylation of Catalytic Lysine of Kinases in Mammalian Cells.

Reversible lysine acetylation is an important post-translational modification (PTM). This process in cells is typically carried out enzymatically by lysine acetyltransferases and deacetylases. The catalytic lysine in the human kinome is highly conserved and ligandable. Small-molecule strategies that enable post-translational acetylation of the catalytic lysine on kinases in a target-selective manner therefore provide tremendous potential in kinase biology. Herein, we report the first small molecule-induced chemical strategy capable of global acetylation of the catalytic lysine on kinases from mammalian cells. By surveying various lysine-acetylating agents installed on a promiscuous kinase-binding scaffold, Ac4 was identified and shown to effectively acetylate the catalytic lysine of >100 different protein kinases from live Jurkat/K562 cells. In order to demonstrate that this strategy was capable of target-selective and reversible chemical acetylation of protein kinases, we further developed six acetylating compounds on the basis of VX-680 (a noncovalent inhibitor of AURKA). Among them, Ac13/Ac14, while displaying excellent in vitro potency and sustained cellular activity against AURKA, showed robust acetylation of its catalytic lysine (K162) in a target-selective manner, leading to irreversible inhibition of endogenous kinase activity. The reversibility of this chemical acetylation was confirmed on Ac14-treated recombinant AURKA protein, followed by deacetylation with SIRT3 (a lysine deacetylase). Finally, the reversible Ac13-induced acetylation of endogenous AURKA was demonstrated in SIRT3-transfected HCT116 cells. By disclosing the first cell-active acetylating compounds capable of both global and target-selective post-translational acetylation of the catalytic lysine on kinases, our strategy could provide a useful chemical tool in kinase biology and drug discovery.

Cu(N2)-Li Battery for Ammonia Synthesis.

The cathodic mechanism of Li-N2 batteries is similar to Li-mediated N2 reduction (LiNR). Herein, the Li-N2, LiNR, and Cu-Li battery were amalgamated to a milliliter-scale Cu(N2)-Li system. The utilization of a lithium anode with lithium oxidation reaction (LiOR), ensures an uninterrupted supply of lithium ions to active N2. LiOR not only enhances electrolyte stability but also reduces voltage by stripping Li ions, in contrast to the inert platinum anode, commonly employed in LiNR. Notably, an unusual observation of ammonia accumulation within the anode chamber elucidates the presence and role of reaction intermediates. The charging process aimed at lithium regeneration faces high polarization, and a cycling procedure involving low-current charging was proposed to improve cycling. This study integrates insights from three distinct research directions to leverage their respective advantages and scientific insights. The Li-N2 battery emerges as a highly advantageous strategy for ammonia synthesis due to the progressiveness of lithium anode.

Cluster sampling and scalable Bayesian optimization with constraints for negative tone development resist model calibration.

As the semiconductor technology node continues to shrink, achieving smaller critical dimension in lithography becomes increasingly challenging. Negative tone development (NTD) process is widely employed in advanced node due to their large process window. However, the unique characteristics of NTD, such as shrinkage effect, make the NTD resist model calibration more complex. Gradient descent (GD) and heuristic methods have been applied for calibration of NTD resist model. Nevertheless, these methods depend on initial parameter selection and tend to fall into local optima, resulting in poor accuracy of the NTD model and massive computational time. In this paper, we propose cluster sampling and scalable Bayesian optimization (BO) with constraints method for NTD resist model calibration. This approach utilizes cluster sampling strategy to enhance the capability for global initial sampling and employs scalable BO with constraints for global optimization of high-dimensional parameter space. With this approach, the calibration accuracy is significantly enhanced in comparison with results from GD and heuristic methods, and the computational efficiency is substantially improved compared with GD. By gearing up cluster sampling strategy and scalable BO with constraints, this method offers a new and efficient resist model calibration.

Three Birds with One Sulfur: Construction of Sulfur-Bridged Porous Organic Polymers for Efficient Gold Adsorption.

Sulfur is a massive byproduct of the petrochemicals industry and hardly employed as a building block for porous organic polymers (POPs). Here, a new family of sulfur-bridged POPs has been prepared via a C-H insertion reaction between sulfur and polycyclic aromatic hydrocarbons. Sulfur works as a solvent, external cross-linker, and porogen simultaneously during the polymerization process. The products demonstrate high porosity and maximum surface area of 1050 m2 g-1 with abundant accessible active sites, contributing to the nanometerization of sulfur and significantly enhancing the inherent affinity between heteroatoms toward soft metal ions. Therefore, they exhibit a high absorption capacity for Au(III) of 3287 mg g-1 and excellent absorption selectivity and removal efficiency via a performance evaluation even in real electronic wastewater. This synthetic strategy to prepare high added-value functional POPs with sulfur not only sheds light on designing high-performance gold adsorption materials and emerging POPs, but also promotes a sustainable development protocol.

Exposure of polyethylene microplastics affects sulfur migration and transformation in anaerobic system.

Polyethylene (PE) microplastic, which is detected in various environmental media worldwide, also inevitably enters wastewater treatment plants, which may have an impact on anaerobic processes in wastewater treatment. In this work, the effect of PE microplastics on anaerobic sulfur transformation was explored. Experimental results showed that PE microplastics addition at 0.1%- 0.5% w/w promoted H2S production by 14.8%-27.4%. PE microplastics enhanced the release of soluble organic sulfur and inorganic sulfate, and promoted the bioprocesses of organosulfur compounds hydrolysis and sulfate reduction. Mechanism analysis showed that PE microplastics increased the content of electroactive components (e.g., protein and humic acids) contained in extracellular polymeric substances (EPS). In particular, PE microplastics increased the proportion and the dipole moment of α-helix, an important component involved in electron transfer contained in extracelluar protein, which provided more electron transfer sites and promoted the α-helix mediated electron transfer. These enhanced the direct electron transfer ability of EPSs, which might explain why PE microplastics facilitated the bioprocesses of organosulfur compounds hydrolysis and sulfate reduction. Correspondingly, metagenomic analysis revealed that PE microplastics increased the relative abundance of S2- producers (e.g., Desulfobacula and Desulfonema) and the relative abundance of functional genes involved in anaerobic sulfur transformation (e.g., PepD and cysD), which were beneficial to H2S production in anaerobic system.

Epicardial SMARCA4 deletion exacerbates cardiac injury in myocardial infarction and is related to the inhibition of epicardial epithelial-mesenchymal transition.

The reactivated adult epicardium produces epicardium-derived cells (EPDCs) via epithelial-mesenchymal transition (EMT) to benefit the recovery of the heart after myocardial infarction (MI). SMARCA4 is the core catalytic subunit of the chromatin re-modeling complex, which has the potential to target some reactivated epicardial genes in MI. However, the effects of epicardial SMARCA4 on MI remain uncertain. This study found that SMARCA4 was activated over time in epicardial cells following MI, and some of activated cells belonged to downstream differentiation types of EPDCs. This study used tamoxifen to induce lineage tracing and SMARCA4 deletion from epicardial cells in Wt1-CreER;Smarca4fl/fl;Rosa26-RFP adult mice. Epicardial SMARCA4 deletion reduces the number of epicardial cells in adult mice, which was related to changes in the activation, proliferation, and apoptosis of epicardial cells. Epicardial SMARCA4 deletion reduced collagen deposition and angiogenesis in the infarcted area, exacerbated cardiac injury in MI. The exacerbation of cardiac injury was related to the inhibition of generation and differentiation of EPDCs. The alterations in EPDCs were associated with inhibited transition between E-CAD and N-CAD during the epicardial EMT, coupled with the down-regulation of WT1, SNAIL1, and PDGF signaling. In conclusion, this study suggests that Epicardial SMARCA4 plays a critical role in cardiac injury caused by MI, and its regulatory mechanism is related to epicardial EMT. Epicardial SMARCA4 holds potential as a novel molecular target for treating MI.

A fundamental study on postmortem submersion interval estimation by metabolomics analyzing of gastrocnemius muscle from submersed rat models in freshwater.

In forensic practice, determining the postmortem submersion interval (PMSI) and cause-of-death of cadavers in aquatic ecosystems has always been challenging task. Traditional approaches are not yet able to address these issues effectively and adequately. Our previous study proposed novel models to predict the PMSI and cause-of-death based on metabolites of blood from rats immersed in freshwater. However, with the advance of putrefaction, it is hardly to obtain blood samples beyond 3 days postmortem. To further assess the feasibility of PMSI estimation and drowning diagnosis in the later postmortem phase, gastrocnemius, the more degradation-resistant tissue, was collected from drowned rats and postmortem submersion model in freshwater immediately after death, and at 1 day, 3 days, 5 days, 7 days, and 10 days postmortem respectively. Then the samples were analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate the dynamic changes of the metabolites. A total of 924 metabolites were identified. Similar chronological changes of gastrocnemius metabolites were observed in the drowning and postmortem submersion groups. The difference in metabolic profiles between drowning and postmortem submersion groups was only evident in the initial 1 day postmortem, which was faded as the PMSI extension. Nineteen metabolites representing temporally-dynamic patterns were selected as biomarkers for PMSI estimation. A regression model was built based on these biomarkers with random forest algorithm, which yielded a mean absolute error (± SE) of 5.856 (± 1.296) h on validation samples from an independent experiment. These findings added to our knowledge of chronological changes in muscle metabolites from submerged vertebrate remains during decomposition, which provided a new perspective for PMSI estimation.

The Impact of Bisphenol A on the Anaerobic Sulfur Transformation: Promoting Sulfur Flow and Toxic H2S Production.

Bisphenol A (BPA), as a typical leachable additive from microplastics and one of the most productive bulk chemicals, is widely distributed in sediments, sewers, and wastewater treatment plants, where active sulfur cycling takes place. However, the effect of BPA on sulfur transformation, particularly toxic H2S production, has been previously overlooked. This work found that BPA at environmentally relevant levels (i.e., 50-200 mg/kg total suspended solids, TSS) promoted the release of soluble sulfur compounds and increased H2S gas production by 14.3-31.9%. The tryptophan-like proteins of microbe extracellular polymeric substances (EPSs) can spontaneously adsorb BPA, which is an enthalpy-driven reaction (ΔH = -513.5 kJ mol-1, ΔS = -1.60 kJ mol-1K -1, and ΔG = -19.52 kJ mol-1 at 35 °C). This binding changed the composition and structure of EPSs, which improved the direct electron transfer capacity of EPSs, thereby promoting the bioprocesses of organic sulfur hydrolysis and sulfate reduction. In addition, BPA presence enriched the functional microbes (e.g., Desulfovibrio and Desulfuromonas) responsible for organic sulfur mineralization and inorganic sulfate reduction and increased the abundance of related genes involved in ATP-binding cassette transporters and sulfur metabolism (e.g., Sat and AspB), which promoted anaerobic sulfur transformation. This work deepens our understanding of the interaction between BPA and sulfur transformation occurring in anaerobic environments.

Solvothermal Preparation of Microporous Polyureas for Au(III) Adsorption.

The enrichment and recovery of gold from wastewater are an alternative method to obtain this noble metal, which benefits reducing hazardous emissions from the conventional ore mining process and reserving natural gold for sustainable development. Inspired by our previous work (Lei et al., Macromol. Rapid Comm. 2022, 2200712), four families of microporous polyureas (mPPUs) with a large surface area (690 m2 g-1) and abundant heteroatom sites have been prepared via the factor-optimized solvothermal protocol. The resultant sample NPU-A starting from 1,5-naphthalene diisocyanate (NDI) and tri(4-aminophenyl) amine (TAPA) exhibits the maximum Au(III) adsorption capacity of 1300 mg g-1 and high selectivity even when the Au(III) concentration is as low as 0.1 mg L-1. This study not only demonstrates the robustness of the high-throughput synthetic strategy but also promotes the investigation of the structure-activity correlation between the mPPU chemical structure and Au(III) adsorption performance.

Model-free finite-time robust control using fractional-order ultra-local model and prescribed performance sliding surface for upper-limb rehabilitation exoskeleton.

To address the trajectory tracking issue of upper-limb rehabilitation exoskeleton with uncertainties and external disturbances, this paper proposes a fractional-order ultra-local model-based model-free finite-time robust controller (FO-FTRC) using predefined performance sliding surface. Different from previous model-free control strategies, a novel multi-input multi-output (MIMO) fractional-order ultra-local model which is a virtual model is proposed to approximate the complex uncertain nonlinear exoskeleton dynamics in a short sliding time window. This allows the design of controller to be independent of any exoskeleton model information and reduces the difficulty of controller design. The developed robust model-free control method incorporates a fractional-order quasi-time delay estimator (FO-QTDE), unknown disturbance estimator (UDE) as well as prescribed performance sliding mode control (PPSMC). The FO-QTDE is utilized to estimate the unknown lumped uncertainties which employs short time delayed knowledge only about the control input. However, the low-pass filter is always added for FO-QTDE when disturbances change fast, which leads to unavoidable estimation error. Then, UDE is designed to further eliminate the estimation error of FO-QTDE to enhance control performance. The PPSMC is constructed to converge sliding surface to zero in a finite time. Besides, the sliding surface is always limited in performance boundaries. After that, the overall system stability and convergence analyses are demonstrated by using the Lyapunov theorem. Finally, with the comparison to other methods of α-variable adaptive model free control (α-AMFC), time-delay estimation-based continuous nonsingular fast terminal sliding mode controller (TDE-CNFTSMC), time delay estimation (TDE)-based model-free fractional-order nonsingular fast terminal sliding mode control (MFF-TSM) and fractional-order proportion-differential (PDß), the co-simulation results on 7-degree-of-freedom (DOF) iReHave upper-limb exoskeleton virtual prototype and experiment results on 2-DOF upper-limb exoskeleton are obtained to illustrate the effectiveness and superiority of the proposed FO-FTRC method.

Light-Activated BF3·Et2O-Promoted Generation of Singlet Oxygen and Cascade Reaction of Unsaturated Amides.

Herein, BF3·Et2O-promoted O-insertion/spirocyclization/fluorination/ring-expansion of unsaturated amides to synthesis of spiro[benzo[b]-[1,4]dioxepine-3,5'-oxazole] skeletons in the presence of natural light and O2 (3Σg-) was reported. Air was the oxygen source of the 1O2-generation and O-insertion reaction under metal-free and mild conditions. BF3·Et2O played multiple roles, such as Lewis acid, activating reagent, and fluorine source in the reported cascade. A mechanism involving 1O2 generation/activation of double bond/O-insertion/spirocyclization/fluorination/ring expansion was supposed.

Improving the Resolution of Flexible Large-Area Tactile Sensors through Machine-Learning Perception.

Industrial robots are the main piece of equipment of intelligent manufacturing, and array-type tactile sensors are considered to be the core devices for their active sensing and understanding of the production environment. A great challenge for existing array-type tactile sensors is the wiring of sensing units in a limited area, the contradiction between a small number of sensing units and high resolution, and the deviation of the overall output pattern due to the difference in the performance of each sensing unit itself. Inspired by the human somatosensory processing hierarchy, we combine tactile sensors with artificial intelligence algorithms to simplify the sensor architecture while achieving tactile resolution capabilities far greater than the number of signal channels. The prepared 8-electrode carbon-based conductive network achieves high-precision identification of 32 regions with 97% classification accuracy assisted by a quadratic discriminant analysis algorithm. Notably, the output of the sensor remains unchanged after 13,000 cycles at 60 kPa, indicating its excellent durability performance. Moreover, the large-area skin-like continuous conductive network is simple to fabricate, cost-effective, and can be easily scaled up/down depending on the application. This work may address the increasing need for simple fabrication, rapid integration, and adaptable geometry tactile sensors for use in industrial robots.

Histone H3K36me3 mediates the genomic instability of Benzo[a]pyrene in human bronchial epithelial cells.

Histone modifications maintain genomic stability and orchestrate gene expression at the chromatin level. Benzo [a]pyrene (BaP) is the ubiquitous carcinogen widely spread in the environment, but the role and regulatory mechanism of histone modification in its toxic effects remain largely undefined. In this study, we found a dose-dependent reduction of histone H3 methylations at lysine4, lysine9, lysine27, lysine36 in HBE cells treated with BaP. We observed that inhibiting H3K27 and H3K36 methylation impaired cell proliferation, whereas the loss of H3K4, H3K9, H3K27, and H3K36 methylation led to increased genomic instability and delayed DNA repair. H3K36 mutation at both H3.1 and H3.3 exhibited the most significant impacts. In addition, we found that the expression of SET domain containing 2 (SETD2), the unique methyltransferase catalyzed H3K36me3, was downregulated by BaP dose-dependently in vitro and in vivo. Knockdown of SETD2 aggravated DNA damage of BaP exposure, which was consistent with the effects of H3K36 mutation. With the aid of chromatin immunoprecipitation (ChIP) -seq and RNA-seq, we found that H3K36me3 was responsible for transcriptional regulation of genes involved in pathways related to cell survival, lung cancer, metabolism and inflammation. The enhanced enrichment of H3K36me3 in genes (CYP1A1, ALDH1A3, ACOXL, WNT5A, WNT7A, RUNX2, IL1R2) was positively correlated with their expression levels, while the reduction of H3K36me3 distribution in genes (PPARGC1A, PDE4D, GAS1, RNF19A, KSR1) were in accordance with the downregulation of gene expression. Taken together, our findings emphasize the critical roles and mechanisms of histone lysine methylation in mediating cellular homeostasis during BaP exposure.

State-of-the-art electrochemical biosensors based on covalent organic frameworks and their hybrid materials.

As the development of global population and industry civilization, the accurate and sensitive detection of intended analytes is becoming an important and great challenge in the field of environmental, medical, and public safety. Recently, electrochemical biosensors have been constructed and used in sensing fields, such as antibiotics, pesticides, specific markers of cancer, and so on. Functional materials have been designed and prepared to enhance detection performance. Among all reported materials, covalent organic frameworks (COFs) are emerging as porous crystalline materials to construct electrochemical biosensors, because COFs have many unique advantages, including large surface area, high stability, atom-level designability, and diversity, to achieve a far better sensing performance. In this comprehensive review, we not only summarize state-of-the-art electrochemical biosensors based on COFs and their hybrid materials but also highlight and discuss some typical examples in detail. We finally provide the challenge and future perspective of COFs-based electrochemical biosensors.