miR-141-3p promotes paclitaxel resistance by attenuating ferroptosis via the Keap1-Nrf2 signaling pathway in breast cancer.

Purpose: Breast cancer poses a huge threat to the lives and health of women worldwide. However, drug resistance makes the treatment of breast cancer challenging. This study aims to investigate the effect of miR-141-3p on paclitaxel resistance and its underlying mechanisms in breast cancer. Methods: Using bioinformatics analysis and qRT-PCR to explore the potential molecule miR-141-3p. Specific binding of miR-141-3p to Keap1 was determined by using a dual luciferase reporter assay. qRT-PCR and Western blot were utilized to observe the expression of miR-141-3p, Keap1, Nrf2, SLC7A11 and GPX4. GSH/GSSG content, MDA content and JC-1 assays were used to observe the ferroptosis levels of breast cancer cells. CCK-8 assay was used to observe the cell viability of breast cancer cells. Tumor subcutaneous transplantation experiment was used to understand the effect of miR-141-3p on paclitaxel resistance in breast cancer in vivo. Results: In the present study, miR-141-3p was found to be highly expressed and associated with poor prognosis in breast cancer. miR-141-3p inhibited Keap1 expression, promoted Nrf2 expression, and facilitated paclitaxel resistance in breast cancer cells. Inhibition of miR-141-3p promoted Keap1 expression, inhibited Nrf2 and its downstream SLC7A11-GSH-GPX4 signaling pathway, as well as promoted ferroptosis in cancer cells, and inhibited paclitaxel and RSL3 resistance. ML385 blocks the effect of miR-141-3p on paclitaxel resistance and ferroptosis resistance in breast cancer cells. In vivo, miR-141-3p mimics promoted paclitaxel resistance, whereas miR-141-3p inhibitors inhibited paclitaxel resistance in breast cancer cells. Conclusion: This work revealed that modulation of the Keap1-Nrf2 signaling pathway by miR-141-3p promoted paclitaxel resistance via regulating ferroptosis in breast cancer cells.

Built-in electrophilic/nucleophilic domain of nitrogen-doped carbon nanofiber-confined Ni2P/Ni3N nanoparticles for efficient urea-containing water-splitting reactions.

Transferring urea-containing waste water to clean hydrogen energy has received increasing attention, while challenges are still faced in the sluggish catalytic kinetics of urea oxidation. Herein, a novel hybrid catalyst of Ni2P/Ni3N embedded in nitrogen-doped carbon nanofiber (Ni2P/Ni3N/NCNF) is developed for energy-relevant urea-containing water-splitting reactions. The built-in electrophilic/nucleophilic domain resulting from the electron transfer from Ni2P to Ni3N accelerates the formation of high-valent active Ni species and promotes favourable urea molecule adsorption. A spectral study and theoretical analysis reveal that the negatively shifted Ni d-band centre in Ni2P/Ni3N/NCNF weakens the adsorption of intermediate CO2 and facilitates its desorption, thereby improving the urea oxidation reaction kinetics. The overall reaction process is also optimized by minimizing the energy barrier of the rate-determining step. Following the stability test, the surface reconstruction of the pre-catalyst is discussed, where an amorphous layer of NiOOH as the real active phase is formed on the surface/interface of Ni2P/Ni3N for urea oxidation. Benefiting from these characteristics, a high current density of 151.11 mA cm-2 at 1.54 V vs. RHE is obtained for urea oxidation catalysed by Ni2P/Ni3N/NCNF, exceeding that of most of the similar catalysts. A low cell voltage of 1.39 V is required to reach 10 mA cm-2 for urea electrolysis, which is about 200 mV less than that of the general water electrolysis. The current work will be helpful for the development of advanced catalysts and their application in the urea-containing waste water transfer to clean hydrogen energy.

Distinguishing contributions of diverse sediment components to vanadium transport, immobilization and transformation in aquifer.

Vanadium (V) occurs in environment naturally and anthropogenically, but little has been understood about its environmental behavior in groundwater aquifer with sediments. This study investigated the pentavalent V [V(V)] transport and transformation under the influence of different sediment components (minerals, organic matter, and microorganisms) through column experiments. All these components played pivotal roles in V immobilization. The synergistic effects of sediment components enhanced V retention compared to individual component. Mineral components, particularly those containing carbonates and metal oxides, predominantly influenced V(V) transport as indicated by XRD analysis. Organic matter, especially under low pH conditions, induced particle aggregation, thereby inhibiting the transport of V(V). The V K-edge X-ray absorption near-edge structure spectroscopy revealed the formation of tetravalent V[V(IV)] in treatments involving organic matter and microorganisms. Notably, organic matter exhibited the capability to directly reduce V(V). The introduction of microorganisms restricted V(V) transfer. V(V) reducing genera (e.g., Brevundimonas, Arenimonas, Xanthobacter) were detected, achieving V(V) reduction to insoluble V(IV). V(V) bioreduction was improved by minerals that promote microbial metabolism with enhanced electron transfer, or by organic matter that increases levels of intracellular nicotinamide adenine dinucleotide and extracellular polymeric substances. This study specifies the contributions of different sediment components to the transportation and transformation of V, deepening our understanding of V biogeochemistry in groundwater aquifer.

Conversion of monocropping to intercropping promotes rhizosphere microbiome functionality and soil nitrogen cycling.

Intercropping can increase soil nutrient availability and provide greater crop yields for intensive agroecosystems. Despite its multiple benefits, how intercropping influences rhizosphere microbiome assemblages, functionality, and complex soil nitrogen cycling is not fully understood. Here, a three-year field experiment was carried out on different cropping system with five fertilization treatments at the main soybean production regions. We found that soybean yields in intercropped systems were on average 17 % greater than in monocropping system, regardless of fertilization treatments. We also found that intercropping systems significant increased network modularity (by 46 %) and functional diversity (by 11 %) than monocropping systems. Metagenomics analyses further indicated intercropping promotes microbiome functional adaptation, particularly enriching core functions related to nitrogen metabolism. Cropping patterns had a stronger influence on the functional genes associated with soil nitrogen cycling (R2 = 0.499). Monocropping systems increased the abundance of functional genes related to organic nitrogen ammonification, nitrogen fixation, and denitrification, while functional guilds of nitrate assimilation (by 28 %), nitrification (by 31 %), and dissimilatory nitrate reduction (by 10.1 %) genes were enriched in intercropping systems. Furthermore, we found that abiotic factors (i.e. AP, pH, and Moisture) are important drivers in shaping soil microbial community assemblage and nitrogen cycling. The functional genes include hzsB, and nrfA, and nxrA that affected by these biotic and abiotic variables were strongly related to crop yield (R2 = 0.076 ~ R2 = 0.249), suggesting a key role for maintaining crop production. We demonstrated that land use conversion from maize monocropping to maize-soybean intercropping diversify rhizosphere microbiome and functionality signatures, and intercropping increased key gene abundance related to soil nitrogen cycling to maintain the advantage of crop yield. The results of this study significantly facilitate our understanding of the complex soil nitrogen cycling processes and lay the foundation for manipulating desired specific functional taxa for improved crop productivity under sustainable intensification.

Multiple pathways of vanadate reduction and denitrification mediated by denitrifying bacterium Acidovorax sp. strain BoFeN1.

Contamination of aquifers by a combination of vanadate [V(V)] and nitrate (NO3-) is widespread nowadays. Although bioremediation of V(V)- and nitrate-contaminated environments is possible, only a limited number of functional species have been identified to date. The present study demonstrates the effectiveness of V(V) reduction and denitrification by a denitrifying bacterium Acidovorax sp. strain BoFeN1. The V(V) removal efficiency was 76.5 ± 5.41 % during 120 h incubation, with complete removal of NO3- within 48 h. Inhibitor experiments confirmed the involvement of electron transport substances and denitrifying enzymes in the bioreduction of V(V) and NO3-. Cyt c and riboflavin were important for extracellular V(V) reduction, with quinone and EPS more significant for NO3- removal. Intracellular reductive compounds including glutathione and NADH directly reduce V(V) and NO3-. Reverse transcription quantitative PCR confirmed the important roles of nirK and napA genes in regulating V(V) reduction and denitrification. Bioaugmentation by strain BoFeN1 increased V(V) and NO3- removal efficiency by 55.3 % ± 2.78 % and 42.1 % ± 1.04 % for samples from a contaminated aquifer. This study proposes new microbial resources for the bioremediation of V(V) and NO3-contaminated aquifers, and contributes to our understanding of coupled vanadium, nitrogen, and carbon biogeochemical processes.

Recent advances in potential therapeutic targets of ferroptosis­associated pathways for the treatment of stroke (Review).

Stroke is a severe neurological disease that is associated with high rates of morbidity and mortality, and the underlying pathological processes are complex. Ferroptosis fulfills a significant role in the progression and treatment of stroke. It is well established that ferroptosis is a type of programmed cell death that is distinct from other forms or types of cell death. The process of ferroptosis involves multiple signaling pathways and regulatory mechanisms that interact with mechanisms inherent to stroke development. Inducers and inhibitors of ferroptosis have been shown to exert a role in the onset of this cell death process. Furthermore, it has been shown that interfering with ferroptosis affects the occurrence of stroke, indicating that targeting ferroptosis may offer a promising therapeutic approach for treating patients of stroke. Hence, the present review aimed to summarize the latest progress that has been made in terms of using therapeutic interventions for ferroptosis as treatment targets in cases of stroke. It provides an overview of the relevant pathways and molecular mechanisms that have been investigated in recent years, highlighting the roles of inducers and inhibitors of ferroptosis in stroke. Additionally, the intervention potential of various types of Traditional Chinese Medicine is also summarized. In conclusion, the present review provides a comprehensive overview of the potential therapeutic targets afforded by ferroptosis­associated pathways in stroke, offering new insights into how ferroptosis may be exploited in the treatment of stroke.

Effects of arsenic on the transport and attachment of microplastics in porous media.

Understanding the impact of arsenic (As(III), inorganic pollutant widely present in natural environments) on microplastics (MPs, one type of emerging contaminants) mobility is essential to predict MPs fate and distribution in soil-groundwater systems, yet relevant research is lacking. This study explored the effects of As(III) copresent in suspensions (0.05, 0.5, and 5 mg/L) on MPs transport/attachment behaviors in porous media containing varied water contents (θ = 100 %, 90 %, and 60 %) under different ionic strengths (5, 10, and 50 mM NaCl) and flow rates (2, 4, and 8 m/day). Despite solution ionic strengths, flow rates, porous media water contents, sizes, and surface charges of MPs, with coexisting humic acid, and in actual water samples, As(III) of three concentrations increased MPs transport in quartz sand and natural sandy soil. The increased electrostatic repulsion between MPs and sand caused by the altered MPs surface charge via the adsorption of As(III) together with steric repulsion from As(III) in solution contributed to the promoted MPs mobility in porous media. The occupying attachment sites by As(III) partially contributed to the increased mobility of MPs with negative surface charge in porous media. Clearly, As(III) coexisting in suspensions would enhance MPs transport in porous media, increasing MPs environment risks.

Undisclosed contribution of microbial assemblages selectively enriched by microplastics to the sulfur cycle in the large deep-water reservoir.

The accumulation of microplastics in reservoirs due to river damming has drawn considerable attention due to their potential impacts on elemental biogeochemical cycling at the watershed scale. However, the effects of plastisphere communities on the sulfur cycle in the large deep-water reservoir remain poorly understood. Here, we collected microplastics and their surrounding environmental samples in the water and sediment ecosystems of Xiaowan Reservoir and found a significant spatiotemporal pattern of microplastics and sulfur distribution in this Reservoir. Based on the microbial analysis, plastic-degrading taxa (e.g., Ralstonia, Rhodococcus) involved in the sulfur cycle were enriched in the plastisphere of water and sediment, respectively. Typical thiosulfate oxidizing bacteria Limnobacter acted as keystone species in the plastisphere microbial network. Sulfate, oxidation reduction potential and organic matter drove the variations of the plastisphere. Environmental filtration significantly affected the plastisphere communities, and the deterministic process dominated the community assembly. Furthermore, predicted functional profiles related to sulfur cycling, compound degradation and membrane transport were significantly enriched in the plastisphere. Overall, our results suggest microplastics as a new microbial niche exert different effects in water and sediment environments, and provide insights into the potential impacts of the plastisphere on the sulfur biogeochemical cycle in the reservoir ecosystem.

Exosomal miRNA-92a derived from cancer-associated fibroblasts promote invasion and metastasis in breast cancer by regulating G3BP2.

Cancer-associated Fibroblasts (CAFs) exert a tumor-promoting effect in various cancers, including breast cancer. CAFs secrete exosomes containing miRNA and proteins, influencing the tumor microenvironment. In this study, we identified CAF-derived exosomes that transport functional miR-92a from CAFs to tumor cells, thereby intensifying the aggressiveness of breast cancer. CAFs downregulate the expression of G3BP2 in breast cancer cells, and a significant elevation in miR-92a levels in CAF-derived exosomes was observed. Both in vitro and in vivo experiments demonstrate that miR-92a enhances breast cancer cell migration and invasion by directly targeting G3BP2, functioning as a tumor-promoting miRNA. We validated that the RNA-binding proteins SNRPA facilitate the transfer of CAF-derived exosomal miR-92a to breast cancer cells. The reduction of G3BP2 protein by CAF-derived exosomes releases TWIST1 into the nucleus, promoting epithelial-mesenchymal transition (EMT) and further exacerbating breast cancer progression. Moreover, CAF-derived exosomal miR-92a induces tumor invasion and metastasis in mice. Overall, our study reveals that CAF-derived exosomal miR-92a serves as a promoter in the migration and invasion of breast cancer cells by reducing G3BP2 and may represent a potential novel tumor marker for breast cancer.

Distinct effects of canopy vs understory and organic vs inorganic N deposition on root resource acquisition strategies of subtropical Moso bamboo plants.

Atmospheric nitrogen (N) deposition inevitably alters soil nutrient status, subsequently prompting plants to modify their root morphology (i.e., adopting a do-it-yourself strategy), mycorrhizal symbioses (i.e., outsourcing strategy), and root exudation (i.e., nutrient-mining strategy) linking with resource acquisition. However, how N deposition influences the integrated pattern of these resource-acquisition strategies remains unclear. Furthermore, most studies in forest ecosystems have focused on understory N and inorganic N deposition, neglecting canopy-associated processes (e.g., N interception and assimilation) and the impacts of organic N on root functional traits. In this study, we compared the effects of canopy vs understory, organic vs inorganic N deposition on eight root functional traits of Moso bamboo plants. Our results showed that N deposition significantly decreased arbuscular mycorrhizal fungi (AMF) colonization, altered root exudation rate and root foraging traits (branching intensity, specific root area, and length), but did not influence root tissue density and N concentration. Moreover, the impacts of N deposition on root functional traits varied significantly with deposition approach (canopy vs. understory), form (organic vs. inorganic), and their interaction, showing variations in both intensity and direction (positive/negative). Furthermore, specific root area and length were positively correlated with AMF colonization under canopy N deposition and root exudation rate in understory N deposition. Root trait variation under understory N deposition, but not under canopy N deposition, was classified into the collaboration gradient and the conservation gradient. These findings imply that coordination of nutrient-acquisition strategies dependent on N deposition approach. Overall, this study provides a holistic understanding of the impacts of N deposition on root resource-acquisition strategies. Our results indicate that the evaluation of N deposition on fine roots in forest ecosystems might be biased if N is added understory.

Soil Geobacteraceae are the key predictors of neurotoxic methylmercury bioaccumulation in rice.

Contamination of rice by the potent neurotoxin methylmercury (MeHg) originates from microbe-mediated Hg methylation in soils. However, the high diversity of Hg methylating microorganisms in soils hinders the prediction of MeHg formation and challenges the mitigation of MeHg bioaccumulation via regulating soil microbiomes. Here we explored the roles of various cropland microbial communities in MeHg formation in the potentials leading to MeHg accumulation in rice and reveal that Geobacteraceae are the key predictors of MeHg bioaccumulation in paddy soil systems. We characterized Hg methylating microorganisms from 67 cropland ecosystems across 3,600 latitudinal kilometres. The simulations of a rice-paddy biogeochemical model show that MeHg accumulation in rice is 1.3-1.7-fold more sensitive to changes in the relative abundance of Geobacteraceae compared to Hg input, which is recognized as the primary parameter in controlling MeHg exposure. These findings open up a window to predict MeHg formation and accumulation in human food webs, enabling more efficient mitigation of risks to human health through regulations of key soil microbiomes.

N6022 attenuates cerebral ischemia/reperfusion injury-induced microglia ferroptosis by promoting Nrf2 nuclear translocation and inhibiting the GSNOR/GSTP1 axis.

Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process of ischemic stroke is complex, and it is crucial to elucidate its molecular mechanisms and explore potential protective drugs. Ferroptosis, a newly recognized form of programmed cell death distinct from necrosis, apoptosis, and autophagy, is closely associated with the pathophysiology of ischemic stroke. N6022, a selective inhibitor of S-nitrosoglutathione reductase (GSNOR), is a "first-in-class" drug for asthma with potential therapeutic applications. However, it remains unclear whether N6022 exerts protective effects in ischemic stroke, and the precise mechanisms of its action are unknown. This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity of SLC7A11-GPX4 system. Furthermore, N6022 interfered with the interaction of GSNOR with GSTP1, thereby boosting the antioxidant capacity of GSTP1 and attenuating ferroptosis. These findings provide novel insights, showing that N6022 attenuates microglial ferroptosis induced by cerebral I/R injury through the promotion of Nrf2 nuclear translocation and inhibition of the GSNOR/GSTP1 axis.

The relationship between cancer associated fibroblasts biomarkers and prognosis of breast cancer: a systematic review and meta-analysis.

Background: To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment. Methodology: PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias. Results: Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor-ß (PDGFR-ß) (P = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) (P < 0.0001), matrix metalloproteinase (MMP) 9 (P < 0.0001), MMP 11 (P < 0.0001) and MMP 13 (P = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of α-smooth muscle actin (α-SMA) (P = 0.0002), podoplanin (PDPN) (P = 0.0008), and PDGFR-ß (P = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR-ß expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2). Conclusions: The high expression of α-SMA, PDPN, PDGFR-ß in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.

Deciphering Vanadium Speciation in Smelting Ash and Adaptive Responses of Soil Microorganisms.

Abundant smelting ash is discharged during pyrometallurgical vanadium (V) production. However, its associated V speciation and resultant ecological impact have remained elusive. In this study, V speciation in smelting ash and its influence on the metabolism of soil microorganisms were investigated. Smelting ashes from V smelters contained abundant V (19.6-115.9 mg/g). V(V) was the dominant species for soluble V, while solid V primarily existed in bioavailable forms. Previously unrevealed V nanoparticles (V-NPs) were prevalently detected, with a peak concentration of 1.3 × 1013 particles/g, a minimal size of 136.0 ± 0.6 nm, and primary constituents comprising FeVO4, VO2, and V2O5. Incubation experiments implied that smelting ash reshaped the soil microbial community. Metagenomic binning, gene transcription, and component quantification revealed that Microbacterium sp. and Tabrizicola sp. secreted extracellular polymeric substances through epsB and yhxB gene regulation for V-NPs aggregation to alleviate toxicity under aerobic operations. The V K-edge X-ray absorption near-edge structure (XANES) spectra suggested that VO2 NPs were oxidized to V2O5 NPs. In the anaerobic case, Comamonas sp. and Achromobacter sp. reduced V(V) to V(IV) for detoxification regulated by the napA gene. This study provides a deep understanding of the V speciation in smelting ash and microbial responses, inspiring promising bioremediation strategies to reduce its negative environmental impacts.

Enhanced Thermal Conductivity of High-Density Polyethylene Composites with Hybrid Fillers of Flaky and Spherical Boron Nitride Particles.

The synergistic effect between different fillers plays a crucial role in determining the performance of composites. In this work, spherical boron nitride (BN) and flaky BN are used as hybrid fillers to improve the thermal conductivity (TC) of high-density polyethylene (HDPE) composites. A series of HDPE composites were prepared by adjusting the mass ratio (1:0, 4:1, 2:1, 1:1, 1:2, 1:4, and 0:1) of spherical BN and flaky BN. The SEM results indicate that the spherical BN (with a particle size of 3 µm) effectively filled the gaps between the flaky BN (with a particle size of 30 µm), leading to the formation of more continuous heat conduction paths with the composite. Remarkably, when the mass ratio of spherical BN to flaky BN was set to 1:4 (with a total BN filling amount of 30 wt%), the TC of the composite could reach up to 1.648 Wm-1K-1, which is obviously higher than that of the composite containing a single filler, realizing the synergistic effect of the hybrid fillers. In addition, the synergistic effect of fillers also affects the thermal stability and crystallization behavior of composites. This work is of great significance for optimizing the application of hybrid BN fillers in the field of thermal management.

Pyrrhotite-dependent microbial reduction and magnetic separation for efficient vanadium detoxification and recovery in contaminated aquifer.

Microbial reduction under anaerobic condition is a promising method for remediating vanadate [V(V)] contamination in aquifers, while V(V) may be re-generated with redox fluctuations. The inability to remove vanadium after remediation has become a key issue limiting bioremediation. In this study, we proposed the use of pyrrhotite, a natural mineral with magnetic properties, to immobilize V(V) to insoluble V(IV) under microbial action and remove vanadium from the aquifer using a magnetic field, which could avoid the problem of V(V) recontamination under redox fluctuating conditions. Up to 49.0 ± 4.7 % of vanadium could be removed from the aquifer by the applied magnetic field, and the vanadium in the aquifer after the reaction was mainly in the acid-extractable and reducible states. pH had a strong effect on the magnetic recovery of V(V), while the influence of initial V(V) concentration was weak. Microbial community structure analysis showed that Thiobacillus, Proteiniphilum, Fermentimonas, and Desulfurivibrio played key roles for V(V) reduction and pyrrhotite oxidation. Structural equation model indicated the positive correlation between these genera with the magnetic recovery of vanadium. Real time-qPCR confirmed the roles of functional genes of V(V) reduction (napA and nirK) and SO42- reduction (dsrA) in such biological processes. This study provides a novel route to sustainable V(V) remediation in aquifers, with synchronous recovery of vanadium resources without rebound.

Therapeutic strategies targeting the NLRP3­mediated inflammatory response and pyroptosis in cerebral ischemia/reperfusion injury (Review).

Ischemic stroke poses a major threat to human health. Therefore, the molecular mechanisms of cerebral ischemia/reperfusion injury (CIRI) need to be further clarified, and the associated treatment approaches require exploration. The NOD­like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome serves an important role in causing CIRI, and its activation exacerbates the underlying injury. Activation of the NLRP3 inflammasome triggers the maturation and production of the inflammatory molecules IL­1ß and IL­18, as well as gasdermin­D­mediated pyroptosis and CIRI damage. Thus, the NLRP3 inflammasome may be a viable target for the treatment of CIRI. In the present review, the mechanisms of the NLRP3 inflammasome in the intense inflammatory response and pyroptosis induced by CIRI are discussed, and the therapeutic strategies that target the NLRP3­mediated inflammatory response and pyroptosis in CIRI are summarized. At present, certain drugs have already been studied, highlighting future therapeutic perspectives.