Transferable and Interpretable Prediction of Site-Specific Dehydrogenation Reaction Rate Constants with NMR Spectra.

Accurate and efficient determination of site-specific reaction rate constants over a wide temperature range remains challenging, both experimentally and theoretically. Taking the dehydrogenation reaction as an example, our study addresses this issue by an innovative combination of machine learning techniques and cost-effective NMR spectra. Through descriptor screening, we identified a minimal set of NMR chemical shifts that can effectively determine reaction rate constants. The constructed model performs exceptionally well on theoretical data sets and demonstrates impressive generalization capabilities, extending from small molecules to larger ones. Furthermore, this model shows outstanding performance when applied to limited experimental data sets, highlighting its robust applicability and transferability. Utilizing the Sure Independence Screening and Sparsifying Operator (SISSO) algorithm, we also present an interpretable rate constant-temperature-NMR (k-T-NMR) relationship with a mathematical formula. This study reveals the great potential of combining machine learning with easily accessible spectroscopic descriptors in the study of reaction kinetics, enabling the rapid determination of reaction rate constants and promoting our understanding of reactivity.

Bioorthogonal microglia-inspired mesenchymal stem cell bioengineering system creates livable niches for enhancing ischemic stroke recovery via the hormesis.

Mesenchymal stem cells (MSCs) experience substantial viability issues in the stroke infarct region, limiting their therapeutic efficacy and clinical translation. High levels of deadly reactive oxygen radicals (ROS) and proinflammatory cytokines (PC) in the infarct milieu kill transplanted MSCs, whereas low levels of beneficial ROS and PC stimulate and improve engrafted MSCs' viability. Based on the intrinsic hormesis effects in cellular biology, we built a microglia-inspired MSC bioengineering system to transform detrimental high-level ROS and PC into vitality enhancers for strengthening MSC therapy. This system is achieved by bioorthogonally arming metabolic glycoengineered MSCs with microglial membrane-coated nanoparticles and an antioxidative extracellular protective layer. In this system, extracellular ROS-scavenging and PC-absorbing layers effectively buffer the deleterious effects and establish a micro-livable niche at the level of a single MSC for transplantation. Meanwhile, the infarct's inanimate milieu is transformed at the tissue level into a new living niche to facilitate healing. The engineered MSCs achieved viability five times higher than natural MSCs at seven days after transplantation and exhibited a superior therapeutic effect for stroke recovery up to 28 days. This vitality-augmented system demonstrates the potential to accelerate the clinical translation of MSC treatment and boost stroke recovery.

Direct lithium extraction from spent batteries for efficient lithium recycling.

The flourishing expansion of the lithium-ion batteries (LIBs) market has led to a surge in the demand for lithium resources. Developing efficient recycling technologies for imminent large-scale retired LIBs can significantly facilitate the sustainable utilization of lithium resources. Here, we successfully extract active lithium from spent LIBs through a simple, efficient, and low-energy-consumption chemical leaching process at room temperature, using a solution comprised of polycyclic aromatic hydrocarbons and ether solvents. The mechanism of lithium extraction is elucidated by clarifying the relationship between the redox potential and extraction efficiency. More importantly, the reclaimed active lithium is directly employed to fabricate LiFePO4 cathode with performance comparable to commercial materials. When implemented in 56 Ah prismatic cells, the cells deliver stable cycling properties with a capacity retention of ∼90% after 1200 cycles. Compared with the other strategies, this technical approach shows superior economic benefits and practical promise. It is anticipated that this method may redefine the recycling paradigm for retired LIBs and drive the sustainable development of industries.

Biologically Self-Assembled Tumor Cell-Derived Cancer Nanovaccines as an All-in-One Platform for Cancer Immunotherapy.

Tumor cell-derived cancer nanovaccines introduce tumor cell-derived components as functional units that endow the nanovaccine systems with some advantages, especially providing all potential tumor antigens. However, cumbersome assembly steps, potential risks of exogenous adjuvants, as well as insufficient lymph node (LN) targeting and dendritic cell (DC) internalization limit the efficacy and clinical translation of existing tumor cell-derived cancer nanovaccines. Herein, we introduced an endoplasmic reticulum (ER) stress inducer α-mangostin (αM) into tumor cells through poly(d, l-lactide-co-glycolide) nanoparticles and harvested biologically self-assembled tumor cell-derived cancer nanovaccines (αM-Exos) based on the biological process of tumor cell exocytosing nanoparticles through tumor-derived exosomes (TEXs). Besides presenting multiple potential antigens, αM-Exos inherited abundant 70 kDa heat shock proteins (Hsp70s) upregulated by ER stress, which can not only act as endogenous adjuvants but also improve LN targeting and DC internalization. Following subcutaneous injection, αM-Exos efficiently migrated to LNs and was expeditiously endocytosed by DCs, delivering tumor antigens and adjuvants to DCs synchronously, which then powerfully triggered antitumor immune responses and established long-term immune memory. Our study exhibited an all-in-one biologically self-assembled tumor cell-derived cancer nanovaccine platform, and the fully featured cancer nanovaccines assembled efficiently through this platform are promising for desirable cancer immunotherapy.

Establishment of portable Pseudomonas aeruginosa detection platform based on one-tube CRISPR/Cas12a combined with recombinase polymerase amplification technology.

Pseudomonas aeruginosa, a common Gram-negative bacterium, is associated with diverse diseases. Its increasing resistance to antibiotics presents challenges in clinical treatment. The predominant diagnostic approach involves conventional biochemical cultures, known for their time and labor intensiveness. Despite progress in isothermal amplification studies, limitations persist, including reliance on specialized equipment, intricate primer design, and aerosol contamination. Therefore, there is a demand for enhanced clinical assays. This study successfully combined RPA and CRISPR/Cas12a techniques. Through a series of experiments involving the design and screening of lasB crRNA, the creation of lasB RPA primers, and the establishment of a streamlined RPA-CRISPR/Cas12a assay, the study developed a one-tube detection method targeting P. aeruginosa's lasB gene. The assay demonstrated inclusive behavior across standard and 21 isolates, while specifically discerning P. aeruginosa from diverse strains. Sensitivity reached 15.9 CFU/reaction. Clinical validation revealed a 97.62% concordance with traditional methods. The one-tube assay's protocol mitigated aerosol contamination. Offering precision, specificity, and sensitivity, this method shows promise for field applications in resource-scarce regions, enabling early detection and improved management of P. aeruginosa infections.

Spectroscopy-Guided Deep Learning Predicts Solid-Liquid Surface Adsorbate Properties in Unseen Solvents.

Accurately and rapidly acquiring the microscopic properties of a material is crucial for catalysis and electrochemistry. Characterization tools, such as spectroscopy, can be a valuable tool to infer these properties, and when combined with machine learning tools, they can theoretically achieve fast and accurate prediction results. However, on the path to practical applications, training a reliable machine learning model is faced with the challenge of uneven data distribution in a vast array of non-negligible solvent types. Herein, we employ a combination of the first-principles-based approach and data-driven model. Specifically, we utilize density functional theory (DFT) to calculate theoretical spectral data of CO-Ag adsorption in 23 different solvent systems as a data source. Subsequently, we propose a hierarchical knowledge extraction multiexpert neural network (HMNN) to bridge the knowledge gaps among different solvent systems. HMNN undergoes two training tiers: in tier I, it learns fundamental quantitative spectra-property relationships (QSPRs), and in tier II, it inherits the fundamental QSPR knowledge from previous steps through a dynamic integration of expert modules and subsequently captures the solvent differences. The results demonstrate HMNN's superiority in estimating a range of molecular adsorbate properties, with an error range of less than 0.008 eV for zero-shot predictions on unseen solvents. The findings underscore the usability, reliability, and convenience of HMNN and could pave the way for real-time access to microscopic properties by exploiting QSPR.

Liensinine alleviates mouse intestinal injury induced by sepsis through inhibition of oxidative stress, inflammation, and cell apoptosis.

Sepsis is a clinical syndrome triggered by an imbalanced host response to pathogens that can lead to multiple organ dysfunction. The immune response and barrier function of the gut play an important role in the pathogenesis and progression of sepsis. This study aimed to explore the potential role of natural alkaloid Liensinine in the treatment of intestinal injury caused by sepsis and its possible molecular mechanism. In this study, a mouse model of sepsis was established by injecting LPS to explore the protective effect of Liensinine on intestinal injury in sepsis. The results showed that Liensinine could reduce the intestinal damage caused by LPS and increase the number of goblet cells. Furthermore, it decreased the release of inflammatory cytokines by inhibiting NF-kB phosphorylation and NLRP3 inflammasome synthesis. Liensinine also reduced the oxidative stress and ROS accumulation caused by LPS, and played an anti-oxidative stress role by regulating the Nrf2/keap1 signaling pathway. In addition, Liensinine alleviated the inhibition of intestinal autophagy caused by LPS by inhibiting the PI3K/Akt/mTOR pathway. And then it reduced the excessive apoptosis of intestinal cells. This study provides valuable insights for sepsis prevention and treatment, offering a potential therapeutic candidate to protect against intestinal injury and regulate the inflammatory response in sepsis.

Malvidin alleviates LPS-induced septic intestinal injury through the nuclear factor erythroid 2-related factor 2/reactive oxygen species/NLRP3 inflammasome pathway.

Emerging evidence suggests that the gastrointestinal tract plays a crucial role in the pathophysiology of sepsis, a leading cause of mortality among patients admitted to the intensive care unit (ICU). Malvidin, belonging to the flavonoid family of compounds, exhibits a range of capabilities including anti-inflammatory and antioxidant properties. Studies have demonstrated that Malvidin exhibits a dose-dependent effect in mitigating sepsis-induced intestinal injury. The advantageous impact of Malvidin in safeguarding against sepsis-induced intestinal injury is associated with its capacity to counteract oxidative stress, inhibit cellular apoptosis, diminish the secretion of pro-inflammatory cytokines, and regulate the synthesis of inflammasomes. The findings indicate that Malvidin, a natural compound, exhibits protective effects on the gut by activating the nuclear factor erythroid 2-related factor 2/reactive oxygen species/NLRP3 inflammasome pathway. These results have significant implications for potential clinical applications and offer valuable insights into the treatment of sepsis-induced intestinal injury.

Leonurine pretreatment protects the heart from myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion (I/R), an important complication of reperfusion therapy for myocardial infarction, is characterized by hyperactive oxidative stress and inflammatory response. Leonurine (4-guanidino-n-butyl syringate, SCM-198), an alkaloid extracted from Herbaleonuri, was previously found to be highly cardioprotective both in vitro and in vivo. Our current study aimed to investigate the effect of SCM-198 preconditioning on myocardial I/R injury in vitro and in vivo, respectively, as well as to decipher the mechanism involved. Rats were pretreated with SCM-198 before subjected to 45 min of myocardial ischemia, which was followed by 24 h of reperfusion. Primary neonatal rat cardiac ventricular myocytes (NRCMs) were exposed to hypoxia (95% N2 + 5% CO2) for 12 h, and then to 12 h reoxygenation so as to mimic I/R. The enzymatic measurements demonstrated that SCM-198 reduced the release of infarction-related enzymes, and the hemodynamic and echocardiography measurements showed that SCM-198 restored cardiac functions, which suggested that SCM-198 could significantly reduce infarct size, maintaining cardiomyocyte morphology, and that SCM-198 pretreatment could significantly reduce cardiomyocytes apoptosis. Moreover, we demonstrated that SCM-198 could exert a cardioprotective effect by reducing reactive oxygen species (ROS) level and Akt phosphorylation while reducing the phosphorylation of p38 and JNK. In addition, the upregulation of p-Akt, Bcl-2/Bax induced by SCM-198 treatment were blocked by PI3K inhibitor LY294002, and the total protein level of Akt was not affected by SCM-198 pretreatment. Our experimental results indicated that SCM-198 could have a cardioprotective effect on I/R injury, which confirmed the utility of SCM-198 preconditioning as a strategy to prevent I/R injury.

Nano-Plumber Reshapes Glymphatic-Lymphatic System to Sustain Microenvironment Homeostasis and Improve Long-Term Prognosis after Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Long-term changes in the microenvironment of the brain contribute to the degeneration of neurological function following TBI. However, current research focuses primarily on short-term modulation during the early phases of TBI, not on the critical significance of long-term homeostasis in the brain microenvironment. Notably, dysfunction of the glymphatic-lymphatic system results in the accumulation of danger/damage-associated molecular patterns (DAMPs) in the brain, which is regarded as the leading cause of long-term microenvironmental disturbances following TBI. Here, a nanostructure, Nano-plumber, that co-encapsulates the microenvironment regulator pro-DHA and the lymphatic-specific growth factor VEGF-C is developed, allowing for a sustainable and orderly regulation of the microenvironment to promote long-term neurological recovery. Nano-plumber reverses the injury microenvironment by suppressing microglia and astrocytes activation and maintaining reduced activation via enhanced glymphatic-lymphatic drainage, and significantly improves the neurological function of rodents with TBI. This study demonstrates that glymphatic-lymphatic system reconstruction is essential for enhancing long-term prognosis following TBI, and that the Nano-plumber developed here may serve as a clinically translatable treatment option for TBI.

Surface-tethered ROS-responsive micelle backpacks for boosting mesenchymal stem cell vitality and modulating inflammation in ischemic stroke treatment.

Mesenchymal stem cells (MSCs) exhibited remarkable therapeutic potential in ischemic stroke due to their exceptional immunomodulatory ability and paracrine effect; they have also been regarded as excellent neuroprotectant delivery vehicles with inflammatory tropism. However, the presence of high levels of reactive oxygen species (ROS) and an oxidative stress environment at the lesion site inhibits cell survival and further therapeutic effects. Using bioorthogonal click chemistry, ROS-responsive luteolin-loaded micelles were tethered to the surface of MSCs. As MSCs migrated to the ischemic brain, the micelles would achieve ROS-responsive release of luteolin to protect MSCs from excessive oxidative damage while inhibiting neuroinflammation and scavenging ROS to ameliorate ischemic stroke. This study provided an effective and prospective therapeutic strategy for ischemic stroke and a framework for a stem cell-based therapeutic system to treat inflammatory cerebral diseases.

Synthetically Lethal Biomimetic Nutri-hijacker Hitchhikes and Reprograms KRAS Mutation-Driven Metabolic Addictions for Pancreatic Ductal Adenocarcinoma Treatment.

Metabolic therapy targeting the metabolic addictions driven by gain-of-function mutations in KRAS is promising in fighting cancer through selective killing of malignant cells without hurting healthy cells. However, metabolic compensation and heterogeneity make current metabolic therapies ineffective. Here, we proposed a biomimetic "Nutri-hijacker" with "Trojan horse" design to induce synthetic lethality in KRAS-mutated (mtKRAS) malignant cells by hitchhiking and reprogramming the metabolic addictions. Nutri-hijacker consisted of the biguanide-modified nanoparticulate albumin that impaired glycolysis and a flavonoid that restrained glutaminolysis after the macropinocytosis of Nutri-hijacker by mtKRAS malignant cells. Nutri-hijacker suppressed the proliferation and spread of mtKRAS malignant cells while lowering tumor fibrosis and immunosuppression. Nutri-hijacker significantly extended the lifespan of pancreatic ductal adenocarcinoma (PDAC)-bearing mice when combined with the hydroxychloroquine-based therapies that failed in clinical trials. Collectively, our findings demonstrated that Nutri-hijacker is a strong KRAS mutation-customized inhibitor and the synthetic lethality based on mtKRAS-driven metabolic addictions might be a promising strategy against PDAC.

Tailored Apoptotic Vesicle Delivery Platform for Inflammatory Regulation and Tissue Repair to Ameliorate Ischemic Stroke.

Apoptotic vesicles (ApoVs) hold great promise for inflammatory regulation and tissue repair. However, little effort has been dedicated to developing ApoV-based drug delivery platforms, while the insufficient targeting capability of ApoVs also limits their clinical applications. This work presents a platform architecture that integrates apoptosis induction, drug loading, and functionalized proteome regulation, followed by targeting modification, enabling the creation of an apoptotic vesicle delivery system to treat ischemic stroke. Briefly, α-mangostin (α-M) was utilized to induce mesenchymal stem cell (MSC) apoptosis while being loaded onto MSC-derived ApoVs as an anti-oxidant and anti-inflammatory agent for cerebral ischemia/reperfusion injury. Matrix metalloproteinase activatable cell-penetrating peptide (MAP), a microenvironment-responsive targeting peptide, was modified on the surface of ApoVs to obtain the MAP-functionalized α-M-loaded ApoVs. Such engineered ApoVs targeted the injured ischemic brain after systemic injection and achieved an enhanced neuroprotective activity due to the synergistic effect of ApoVs and α-M. The internal protein payloads of ApoVs, upon α-M activation, were found engaged in regulating immunological response, angiogenesis, and cell proliferation, all of which contributed to the therapeutic effects of ApoVs. The findings provide a universal framework for creating ApoV-based therapeutic drug delivery systems for the amelioration of inflammatory diseases and demonstrate the potential of MSC-derived ApoVs to treat neural injury.

A "tug-of-war" effect tunes Li-ion transport and enhances the rate capability of lithium metal batteries.

"Solvent-in-salt" electrolytes (high-concentration electrolytes (HCEs)) and diluted high-concentration electrolytes (DHCEs) show great promise for reviving secondary lithium metal batteries (LMBs). However, the inherently sluggish Li+ transport of such electrolytes limits the high-rate capability of LMBs for practical conditions. Here, we discovered a "tug-of-war" effect in a multilayer solvation sheath that promoted the rate capability of LMBs; the pulling force of solvent-nonsolvent interactions competed with the compressive force of Li+-nonsolvent interactions. By elaborately manipulating the pulling and compressive effects, the interaction between Li+ and the solvent was weakened, leading to a loosened solvation sheath. Thereby, the developed electrolytes enabled a high Li+ transference number (0.65) and a Li (50 µm)‖NCM712 (4 mA h cm-2) full cell exhibited long-term cycling stability (160 cycles; 80% capacity retention) at a high rate of 0.33C (1.32 mA cm-2). Notably, Li (50 µm)‖LiFePO4 (LFP; 17.4 mg cm-2) cells with a designed electrolyte reached a capacity retention of 80% after 1450 cycles at a rate of 0.66C. An 6 Ah Li‖LFP pouch cell (over 250 W h kg-1) showed excellent cycling stability (130 cycles, 96% capacity retention) under practical conditions. This design concept for an electrolyte provides a promising path to build high-energy-density and high-rate LMBs.

Cyclopentylmethyl Ether, a Non-Fluorinated, Weakly Solvating and Wide Temperature Solvent for High-Performance Lithium Metal Battery.

While recent work demonstrates the advantages of weakly solvating solvents in enhancing the cyclability of LMBs, both new designs and design strategies for high performance weakly solvating solvent, especially physicochemical properties, are still lacking. Here, we propose a molecular design to tune the solvating power and physicochemical properties of non-fluorinated ether solvent. The resulting cyclopentylmethyl ether (CPME) have a weak solvating power and wide liquid-phase temperature range. By optimizing the salt concentration, the CE is further promoted to 99.4 %. Besides, the improved electrochemical performance of Li-S battery in CPME-based electrolytes is obtained at -20 °C. The Li||LFP (17.6 mg cm-2 ) battery with developed electrolyte maintains >90 % of the original capacity over 400 cycles. Our design concept for solvent molecule provides a promising pathway to non-fluorinated electrolytes with weakly solvating power and wide temperature window for high-energy-density LMBs.

Theoretical prediction of nanomolar and sequence-selective binding of synthetic supramolecular cucurbit[7]uril to N-terminal Leu-containing tripeptides.

Molecular recognition towards peptides and proteins with high affinity by synthetic supramolecular hosts is important but challenging. In this work, we investigate the molecular recognition of the synthetic cucurbit[7]uril (CB[7]) to 17 designed N-terminal Leu-containing tripeptides in aqueous medium by molecular dynamics (MD) simulation and screen out tripeptides with high binding affinity. It is found that, compared to LGG, only the third residue is Arg (R), the binding affinity of CB[7] to LGR reaches nanomolar level with binding equilibrium constant (Ka) of 1.1 × 109 M-1. The CB[7] recognition to the N-terminal Leu-containing tripeptides is highly sequence dependent; whether changing the sequence order (from LGR to LRG) or increasing the sequence length (from LGR to LGGR), Ka decreases by about three orders of magnitude. Interestingly, substituting N-terminal Leu for its isomer Ile, the binding of CB[7] to tripeptides weakens significantly with Ka decreasing by 3-8 orders of magnitude. Thus CB[7] can effectively distinguish N-terminal Leu-containing tripeptides from N-terminal Ile-containing tripeptides. Importantly, we predict that when R is as C-terminus, regardless of N-terminal residue being of aromatic type or Leu, the binding strength is always close to the nanomolar level. Therefore, R can be introduced to rationally design novel peptides with high binding affinity to CB[7] in practical applications.

Spatial Effects of Digital Transformation, PM2.5 Exposure, Economic Growth and Technological Innovation Nexus: PM2.5 Concentrations in China during 2010-2020.

Digital transformation can increase lending by commercial banks, which may have an impact on economic development and technological progress, thus affecting air pollution. However, a limited amount of literature has discussed the impact of the digital transformation of commercial banks (DTCB) on air pollution. Based on city-level data from 2010 to 2020, this study used a spatial Durbin model to explore the spatial effects of DTCB on air pollution. This study shows that DTCB significantly increases air pollution in local and surrounding cities. Heterogeneity analysis shows that DTCB increases local and surrounding city air pollution in non-innovative cities and cities with low digital economy development. However, in innovative cities and cities with high digital economy development, DTCB reduces PM2.5 emissions in local and surrounding cities. Mechanism analysis shows that DTCB has no significant impact on technological innovation, but significantly promotes economic development, thus increasing air pollution. From the perspective of DTCB, this paper deepens the research on digital finance and air pollution. Against the background of DTCB, the government should guide commercial banks to apply digital technology to increase lending for technology innovation and promote DTCB to achieve the dual goals of economic development and improvement in air quality.

Reprogramming systemic and local immune function to empower immunotherapy against glioblastoma.

The limited benefits of immunotherapy against glioblastoma (GBM) is closely related to the paucity of T cells in brain tumor bed. Both systemic and local immunosuppression contribute to the deficiency of tumor-infiltrating T cells. However, the current studies focus heavily on the local immunosuppressive tumor microenvironment but not on the co-existence of systemic immunosuppression. Here, we develop a nanostructure named Nano-reshaper to co-encapsulate lymphopenia alleviating agent cannabidiol and lymphocyte recruiting cytokine LIGHT. The results show that Nano-reshaper increases the number of systemic T cells and improves local T-cell recruitment condition, thus greatly increasing T-cell infiltration. When combined with immune checkpoint inhibitor, this therapeutic modality achieves 83.3% long-term survivors without recurrence in GBM models in male mice. Collectively, this work unveils that simultaneous reprogramming of systemic and local immune function is critical for T-cell based immunotherapy and provides a clinically translatable option for combating brain tumors.

Quantifying the effect of administrative approval reforms on SO2 emissions: a quasi-experiment in Chinese cities.

The effects of the Administrative Examination and Approval System Reform on economic growth and entry of businesses have drawn much attention. However, few scholars pay attention to the impacts of this policy on SO2 emissions. Keeping in view the existing research gap, a spatial difference-in-difference (SDID) model is employed to assess the effects of the Administrative Examination and Approval System Reform on SO2 emissions in 297 Chinese cities during the period 1995-2020 from the perspective of spatial spillover effects. The results show that the establishment of Administrative Examination and Approval Center (AEAC) has significantly positive effects on the local SO2 emissions. The significant indirect (spatial spillover) effects are confirmed. That is, the establishment of AEAC of a given city has a significant positive impact on the SO2 emissions of neighboring cities. The findings are confirmed by several robustness tests. Our study findings have significant implications for the cross-border coordination of environmental policies that aim to improve the quality of the environment across borders.

Abamectin causes cardiac dysfunction in carp via inhibiting redox equilibrium and resulting in immune inflammatory response and programmed cell death.

This study aims to investigate the effects of environmentally relevant concentrations of abamectin on the cardiac function of carp and the potential mechanisms. Here, male carp were exposed to abamectin, and cardiac function-related enzymatic markers were examined. Cardiac histopathology, redox equilibrium, inflammation, and cell death were evaluated. Abamectin exposure caused cardiac dysfunction by upregulating lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK), creatine Kinase MB isoenzyme (CK-MB) and white blood cells (WBCs), and decreasing red blood cells (RBCs) and hemoglobin (Hb). DHE staining and biochemical assays revealed that abamectin caused ROS release and oxidative stress by inhibiting Nrf2-ARE pathway. Histopathological and real-time fluorescence quantitative PCR (RT-qPCR) assays revealed that abamectin caused myocardial fiber swelling and inflammatory cell infiltration, enhanced pro-inflammatory cytokines tumor necrosis factor-α (Tnf-α), interleukin-1 beta (Il-1ß), and Il-6 levels and attenuated anti-inflammatory cytokines Il-10 and transforming growth factor beta 1 (Tgf-ß1) through activating NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa-B (NF-κB) pathway. Tunel staining showed that abamectin triggered cardiac apoptosis via activating p53-mediated mitochondrial apoptosis with elevated bcl2-associated X (Bax), reduced B-cell lymphoma-2 (Bcl-2), and activated Caspase-9 and Caspase-3. Immunoblot analysis revealed that abamectin activated autophagic flow by inhibiting mammalian target of rapamycin (mTOR), resulting in the conversion of LC3B from LC3-I to LC3-II, elevation of autophagy protein 5 (Atg5), and reduction of p62. Overall, abamectin caused cardiac dysfunction in carp via inhibiting redox equilibrium and resulting in immune inflammatory response and programmed cell death.