Post-modification of covalent organic framework functionalized aminated carbon nanotubes with active site (Fe) for the sensitive detection of luteolin.

In this research, the TT-COF(Fe)@NH2-CNTs was innovatively prepared through a post-modification synthetic process functionalized TT-COF@NH2-CNTs with active site (Fe), where TT-COF@NH2-CNTs was prepared via a one-pot strategy using 5,10,15,20-tetrakis (para-aminophenyl) porphyrin (TTAP), 2,3,6,7-tetra (4-formylphenyl) tetrathiafulvalene (TTF) and aminated carbon nanotubes (NH2-CNTs) as raw materials. The complex TT-COF(Fe)@NH2-CNTs material possessed porous structures, outstanding conductivity and rich catalytic sites. Thus, it can be adopted to construct electrochemical sensor with glassy carbon electrode (GCE). The TT-COF(Fe)@NH2-CNTs/GCE can selectively detect luteolin (Lu) with a wide linear plot ranging from 0.005 to 3 µM and a low limit of detection (LOD) of 1.45 nM (S/N = 3). The Lu residues in carrot samples were determined using TT-COF(Fe)@NH2-CNTs sensor and UV-visible (UV-Vis) approach. This TT-COF(Fe)@NH2-CNTs/GCE sensor paves the way for the quantification of Lu through a cost-efficient and sensitive electrochemical approach, which can make a significant step in the sensing field based on crystalline COFs.

A supramolecular hydrogel leveraging hierarchical multi-strength hydrogen-bonds hinged strategy achieving a striking adhesive-mechanical balance.

To obtain high-performance tissue-adhesive hydrogel embodying excellent mechanical integrity, a supramolecular hydrogel patch is fabricated through in situ copolymerization of a liquid-liquid phase separation precursor composed of self-complementary 2-2-ureido-4-pyrimidone-based monomer and acrylic acid coupled with subsequent corporation of bioactive epigallocatechin gallate. Remarkably, the prepared supramolecular hydrogel leverages hierarchical multi-strength hydrogen-bonds hinged strategy assisted by alkyl-based hydrophobic pockets, broadening the distribution of binding strength of physical junctions, striking a canonical balance between superb mechanical performance and robust adhesive capacity. Ultimately, the fabricated supramolecular hydrogel patch stands out as a high stretchability (1500 %), an excellent tensile strength (2.6 MPa), a superhigh toughness (12.6 MJ m-3), an instant and robust tissue adhesion strength (263.2 kPa for porcine skin), the considerable endurance under cyclic loading and reversible adhesion, a superior burst pressure tolerance (108 kPa) to those of commercially-available tissue sealants, and outstanding anti-swelling behavior. The resultant supramolecular hydrogel patch demonstrates the rapid hemorrhage control within 60 s in liver injury and efficient wound closure and healing effects with alleviated inflammation and reduced scarring in full-thickness skin incision, confirming its medical translation as a promising self-rescue tissue-adhesive patch for hemorrhage prevention and sutureless wound closure.

The role of sulfur cycle in new particle formation: Cycloaddition reaction of SO3 to H2S.

The chemistry of sulfur cycle contributes significantly to the atmospheric nucleation process, which is the first step of new particle formation (NPF). In the present study, cycloaddition reaction mechanism of sulfur trioxide (SO3) to hydrogen sulfide (H2S) which is a typical air pollutant and toxic gas detrimental to the environment were comprehensively investigate through theoretical calculations and Atmospheric Cluster Dynamic Code simulations. Gas-phase stability and nucleation potential of the product thiosulfuric acid (H2S2O3, TSA) were further analyzed to evaluate its atmospheric impact. Without any catalysts, the H2S + SO3 reaction is infeasible with a barrier of 24.2 kcal/mol. Atmospheric nucleation precursors formic acid (FA), sulfuric acid (SA), and water (H2O) could effectively lower the reaction barriers as catalysts, even to a barrierless reaction with the efficiency of cis-SA > trans-FA > trans-SA > H2O. Subsequently, the gas-phase stability of TSA was investigated. A hydrolysis reaction barrier of up to 61.4 kcal/mol alone with an endothermic isomerization reaction barrier of 5.1 kcal/mol under the catalytic effect of SA demonstrates the sufficient stability of TSA. Furthermore, topological and kinetic analysis were conducted to determine the nucleation potential of TSA. Atmospheric clusters formed by TSA and atmospheric nucleation precursors (SA, ammonia NH3, and dimethylamine DMA) were thermodynamically stable. Moreover, the gradually decreasing evaporation coefficients for TSA-base clusters, particularly for TSA-DMA, suggests that TSA may participate in NPF where the concentration of base molecules are relatively higher. The present new reaction mechanism may contributes to a better understanding of atmospheric sulfur cycle and NPF.

Relative humidity-dependent evolution of molecular composition of α-pinene secondary organic aerosol upon heterogeneous oxidation by hydroxyl radicals.

Heterogeneous oxidation by gas-phase oxidants is an important chemical transformation pathway of secondary organic aerosol (SOA) and plays an important role in controlling the abundance, properties, as well as climate and health impacts of aerosols. However, our knowledge on this heterogeneous chemistry remains inadequate. In this study, the heterogeneous oxidation of α-pinene ozonolysis SOA by hydroxyl (OH) radicals was investigated under both low and high relative humidity (RH) conditions, with an emphasis on the evolution of molecular composition of SOA and its RH dependence. It is found that the heterogeneous oxidation of SOA at an OH exposure level equivalent to 12 hr of atmospheric aging leads to particle mass loss of 60% at 25% RH and 95% at 90% RH. The heterogeneous oxidation strongly changes the molecular composition of SOA. The dimer-to-monomer signal ratios increase dramatically with rising OH exposure, in particular under high RH conditions, suggesting that aerosol water stimulates the reaction of monomers with OH radicals more than that of dimers. In addition, the typical SOA tracer compounds such as pinic acid, pinonic acid, hydroxy pinonic acid and dimer esters (e.g., C17H26O8 and C19H28O7) have lifetimes of several hours against heterogeneous OH oxidation under typical atmospheric conditions, which highlights the need for the consideration of their heterogeneous loss in the estimation of monoterpene SOA concentrations using tracer-based methods. Our study sheds lights on the heterogeneous oxidation chemistry of monoterpene SOA and would help to understand their evolution and impacts in the atmosphere.

Transmission of multidrug-resistant tuberculosis in Jiangxi, China, and associated risk factors.

In order to effectively combat the urgent threat of multidrug-resistant tuberculosis (MDR-TB), it is imperative to gain a comprehensive understanding of the drug-resistant profiles, transmission dynamics, and associated risk factors. Our study encompassed a population-based retrospective analysis with 130 MDR-TB patients from 2018 to 2021. The research methodology incorporated whole-genome sequencing, drug susceptibility testing , and logistic regression analysis to discern the risk factors of genomic clustering linked to recent transmission. The findings from phenotypic drug resistance assessments revealed notable resistance rates: ethambutol at 62.3% (81/130), streptomycin at 72.3% (94/130), levofloxacin at 51.5% (67/130), and moxifloxacin at 50.0% (65/130). Furthermore, among all patients, 38 individuals (29.23%, 38/130) were found to be part of 17 clusters, indicating instances of recent MDR-TB transmission. The genomic clustering patients were deeply investigated. Lineage 2.2.1 was established as the primary sub-lineage (86.15%, 112/130), followed by lineage 4 (9.23%, 12/130). Moreover, the logistic regression analysis underscored that unemployment, farming occupations, and prior TB treatment were identified as significant risk factors for recent transmission. IMPORTANCE: The high prevalence of multidrug-resistant tuberculosis (MDR-TB) in Jiangxi Province highlights the importance of understanding the genetic background and drug resistance patterns of these strains. This knowledge is crucial for developing effective control methods. Furthermore, in light of the significance of preventing transmission among tuberculosis patients, whole-genome sequencing was utilized to investigate the recent transmission of MDR-TB and identify associated risk factors. The findings revealed that individuals in the farming sector, those who are unemployed, and patients with a history of tuberculosis treatment are at elevated risk. Consequently, targeted public interventions for these at-risk groups are imperative.

Macrophages dying from ferroptosis promote microglia-mediated inflammatory responses during spinal cord injury.

The neurological deficits following traumatic spinal cord injury are associated with severe patient disability and economic consequences. Currently, an increasing number of studies are focusing on the importance of ferroptosis during acute organ injuries. However, the spatial and temporal distribution patterns of ferroptosis during SCI and the details of its role are largely unknown. In this study, in vivo experiments revealed that microglia are in close proximity to macrophages, the major cell type that undergoes ferroptosis following SCI. Furthermore, we found that ferroptotic macrophages aggravate SCI by inducing the proinflammatory properties of microglia. In vitro studies further revealed ferroptotic macrophages increased the expression of IL-1ß, IL-6, and IL-23 in microglia. Mechanistically, due to the activation of the NF-κB signaling pathway, the expression of IL-1ß and IL-6 was increased. In addition, we established that increased levels of oxidative phosphorylation cause mitochondrial reactive oxygen species generation and unfolded protein response activation and trigger an inflammatory response marked by an increase in IL-23 production. Our findings identified that targeting ferroptosis and IL-23 could be an effective strategy for promoting neurological recovery after SCI.

Epigenomic and transcriptomic profiling of solitary fibrous tumors identifies site-specific patterns and candidate genes regulated by DNA methylation.

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm which can arise at any anatomic site and is characterized by recurrent NAB2::STAT6 fusions and metastatic progression in 10-30%. The cell of origin has not been identified. Despite some progress in understanding the contribution of heterogeneous fusion types and secondary mutations to SFT biology, epigenetic alterations in extrameningeal SFT remain largely unexplored, and most sarcoma research to date has focused on the use of methylation profiling for tumor classification. We interrogated genome-wide DNA methylation in 79 SFTs to identify informative epigenetic changes. RNA-seq data from targeted panels and data from the Cancer Genome Atlas (TCGA) were used for orthogonal validation of selected findings. In unsupervised clustering analysis, the top 500 most variable CpGs segregated SFTs by primary anatomic site. Differentially methylated genes (DMGs) associated with primary SFT site included EGFR, TBX15, multiple HOX genes and their cofactors EBF1, EBF3, and PBX1, as well as RUNX1 and MEIS1. Of the 20 DMGs that were interrogated on the RNA-seq panel, twelve were significantly differentially expressed according to site. However, with the exception of TBX15, most of these also showed differential expression according to NAB2::STAT6 fusion type, suggesting that the fusion oncogene contributes to transcriptional regulation of these genes. Transcriptomic data confirmed an inverse correlation between gene methylation and the expression of TBX15 in both SFT and TCGA sarcomas. TBX15 also showed differential mRNA expression and 5' UTR methylation between tumors located in different anatomic sites in TCGA data. In all analyses, TBX15 methylation and mRNA expression retained the strongest association with tissue of origin in SFT and other sarcomas, suggesting a possible marker to distinguish metastatic tumors from new primaries without genomic profiling. Epigenetic signatures may further help to identify SFT progenitor cells at different anatomic sites.

Prescribed performance dynamic surface control based on dual extended state observer for 2-dof hydraulic cutting arm.

In tunnel section forming operations, the boom-type roadheader tracking target trajectory with high precision is greatly significant in avoiding over and under excavation and improving excavation efficiency. However, there exist complex cutting loads, measurement noise, and model uncertainties, seriously degrading the tracking performance of traditional nominal model-based controllers. Hence, this study first fully analyzes the kinematics of all members of the cutting mechanism and establishes its complete multi-body dynamic model using the Lagrange method. Furthermore, a dual extended state observer is designed to estimate the mechanical system's angular velocity and unmodeled disturbances and actuators' uncertain nonlinearities. In particular, introducing a nonlinear filter replaces the traditional first-order filter in dynamic surface technology, overcoming the "explosion of complexity" while attenuating the conservatism of gains tuning. Then, a dual extended state observer-based prescribed performance dynamic surface controller is developed for roadheaders for the first time. Simultaneously, integrating an improved error transformation function into controller design effectively avoids the online computational burden caused by traditional logarithmic operations. Utilizing Lyapunov theory, the cutting system's prescribed transient response and steady-state performance are guaranteed. Finally, the proposed controller's effectiveness is verified by comparative experiments on the roadheader.

Protective and Damaging Mechanisms of Neuromelanin-Like Nanoparticles and Iron in Parkinson's Disease.

Parkinson's disease (PD) pathology speculates that neuromelanin (NM) and iron ions play a significant role in physiological and pathological conditions of PD. Because the difficult accessibility of NM has limited targeted research, synthetic melanin-like nanoparticles have been used to instead. In this report, the eumelanin and pheomelanin-like polydopamine (PDA) nanoparticles are prepared that can be used to simulate natural NM with or without chelating iron ion and studied the redox effects in vitro and in vivo on neuronal cells and PD. The synthetic pheomelanin-like PDA nanoparticles have much stronger redox activity than eumelanin-like PDA nanoparticles without or with iron ion. They can protect neurons by scavenging reactive oxygen species (ROS), while cause neuronal cell death and PD due to excessive binding of iron ions. This work provides new evidence for the relationship among two structural components of NM and iron in PD as well as displays the different effects on the roles of eumelanin and pheomelanin in redox activity under physiological or pathological conditions, which provide a new effective choice for cellular and animal models of PD and offer theoretical guidance for targeted treatment and mechanism research on PD.

Scalable Hierarchically Structured Materials from a Multiscale Particle System Enabled by Microscaffolds.

Structural hierarchy is the key to manufacturing multiscale particle-based composite materials. A novel manufacturing method was developed to generate scalable hierarchical structures in concrete. The new method used 3D-printed microscaffolds to interact with the multiscale particle packing in concrete, resulting in a structured lightweight composite material. The size of internal members can vary by more than two orders of magnitude, to adapt to different applications. Based on compression tests and microstructural investigation by optical microscope and quantitative nanomechanical mapping, we found that the new material is 63.93% more efficient in energy absorption capacity compared with traditional lightweight concrete. Our experimental trials also showed that introducing structural hierarchy can reduce the consumption of cementitious material in the system by up to 14% and significantly reduce the use of scaffolds. The method could be applied to a board spectrum of multiscale particle-based materials, such as dental cement and bone implant materials, to improve material performance and efficiency in medical and construction applications.

Discovery of ß-nitrostyrene derivatives as potential quorum sensing inhibitors for biofilm inhibition and antivirulence factor therapeutics against Serratia marcescens.

Quorum sensing (QS) inhibition has emerged as a promising target for directed drug design, providing an appealing strategy for developing antimicrobials, particularly against infections caused by drug-resistant pathogens. In this study, we designed and synthesized a total of 33 ß-nitrostyrene derivatives using 1-nitro-2-phenylethane (NPe) as the lead compound, to target the facultative anaerobic bacterial pathogen Serratia marcescens. The QS-inhibitory effects of these compounds were evaluated using S. marcescens NJ01 and the reporter strain Chromobacterium violaceum CV026. Among the 33 new ß-nitrostyrene derivatives, (E)-1-methyl-4-(2-nitrovinyl)benzene (m-NPe, compound 28) was proven to be a potent inhibitor that reduced biofilm formation of S. marcescens NJ01 by 79%. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) results revealed that treatment with m-NPe (50 µg/ml) not only enhanced the susceptibility of the formed biofilms but also disrupted the architecture of biofilms by 84%. m-NPe (50 µg/ml) decreased virulence factors in S. marcescens NJ01, reducing the activity of protease, prodigiosin, and extracellular polysaccharide (EPS) by 36%, 72%, and 52%, respectively. In S. marcescens 4547, the activities of hemolysin and EPS were reduced by 28% and 40%, respectively, outperforming the positive control, vanillic acid (VAN). The study also found that the expression levels of QS- and biofilm-related genes (flhD, fimA, fimC, sodB, bsmB, pigA, pigC, and shlA) were downregulated by 1.21- to 2.32-fold. Molecular dynamics analysis showed that m-NPe could bind stably to SmaR, RhlI, RhlR, LasR, and CviR proteins in a 0.1 M sodium chloride solution. Importantly, a microscale thermophoresis (MST) test revealed that SmaR could be a target protein for the screening of a quorum sensing inhibitor (QSI) against S. marcescens. Overall, this study highlights the efficacy of m-NPe in suppressing the virulence factors of S. marcescens, identifying it as a new potential QSI and antibiofilm agent capable of restoring or improving antimicrobial drug sensitivity.

Antibacterial activity and mechanism of Stevia extract against antibiotic-resistant Escherichia coli by interfering with the permeability of the cell wall and the membrane.

Natural plant-derived compounds with broad-spectrum antimicrobial activity have become an effective strategy against multidrug-resistant bacteria. The present study was designed to compare the antibacterial activity of six chlorogenic acid (CA) isomers extracted from stevia and investigated the underlying antibacterial mechanisms involved. The results indicated that isochlorogenic acid C (ICAC) exhibited the strongest antibacterial activity against the tested bacteria, especially E. coli, at a 2 mg/mL minimum inhibitory concentration (MIC) and 8 mg/mL minimum bactericidal concentration (MBC). At the MBC, ICAC inhibited 72.66% of the clinical multidrug-resistant strains. Scanning electron microscopy (SEM) revealed that ICAC induced considerable morphological alterations in E. coli ATCC25922 and C4E2. The significant increase in the activity of extracellular alkaline phosphatase (AKP) indicated that ICAC damages the permeability of the bacterial cell wall. Additionally, the intracellular membrane (IM) permeability and the content of lipopolysaccharide (LPS), a main component of the outer membrane (OM), were determined. The significant decrease in LPS content and increased leakage of intracellular proteins and K+ from E. coli indicated that ICAC could induce the exfoliation of OM and disrupt IM permeability, resulting in the loss of barrier function. The uptake of propidium iodide (PI), a compromised cell membrane nucleic acid stain, and confocal laser scanning microscopy (CLSM) further demonstrated that ICAC disrupted IM integrity. Moreover, the bactericidal effect and damage to bacterial microstructural function occurred in a dose-dependent manner. These data demonstrate that ICAC has excellent antibacterial activity and is a promising approach for overcoming the antibiotic resistance of pathogenic bacteria.

MEF2C Alleviates Postoperative Cognitive Dysfunction by Repressing Ferroptosis.

BACKGROUND: Ferroptosis, a form of programmed cell death featured by lipid peroxidation, has been proposed as a potential etiology for postoperative cognitive dysfunction (POCD). Myocyte-specific enhancer factor 2C (MEF2C), a transcription factor expressed in various brain cell types, has been implicated in cognitive disorders. This study sought to ascertain whether MEF2C governs postoperative cognitive capacity by affecting ferroptosis. METHODS: Transcriptomic analysis of public data was used to identify MEF2C as a candidate differentially expressed gene in the hippocampus of POCD mice. The POCD mouse model was established via aseptic laparotomy under isoflurane anesthesia after treatment with recombinant adeno-associated virus 9 (AAV9)-mediated overexpression of MEF2C and/or the glutathione peroxidase 4 (GPX4) inhibitor RSL3. Cognitive performance, Nissl staining, and ferroptosis-related parameters were assessed. Dual-luciferase reporter gene assays and chromatin immunoprecipitation assays were implemented to elucidate the mechanism by which MEF2C transcriptionally activates GPX4. RESULTS: MEF2C mRNA and protein levels decreased in the mouse hippocampus following anesthesia and surgery. MEF2C overexpression ameliorated postoperative memory decline, hindered lipid peroxidation and iron accumulation, and enhanced antioxidant capacity, which were reversed by RSL3. Additionally, MEF2C was found to directly bind to the Gpx4 promoter and activate its transcription. CONCLUSIONS: Our findings suggest that MEF2C may be a promising therapeutic target for POCD through its negative modulation of ferroptosis.

Reconfigurable Assembly of Planar Colloidal Molecules via Chemical Reaction and Electric Polarization.

Colloidal molecules, ordered structures assembled from micro- and nanoparticles, serve as a valuable model for understanding the behavior of real molecules and for constructing materials with tunable properties. In this work, we introduce a universal strategy for assembling colloidal molecules consisting of a central active particle surrounded by several passive particles as ligands. During the assembly process, active particles attract the surrounding passive particles through phoresis and osmosis resulting from the chemical reactions on the surface of the active particles, while passive particles repel each other due to the electric polarization induced by an alternating current (AC) electric field. By carefully selecting particles of varying structures and sizes, we have assembled colloidal molecules of symmetric and asymmetric dimers, trimers, and multimers. Furthermore, the coordination number of these colloidal molecules can be regulated in real time and in situ by tuning the interaction forces between the constituent particles. Brownian dynamics simulations reproduced the formation of the colloidal molecules and validated that the self-assembly arises from chemically induced attraction and electrical dipolar repulsion. This strategy for reconfigurable colloidal assemblies poses the potential for designing adaptive micro-nanomachines.

Decellularised extracellular matrix-based injectable hydrogels for tissue engineering applications.

Decellularised extracellular matrix (dECM) is a biomaterial derived from natural tissues that has attracted considerable attention from tissue engineering researchers due to its exceptional biocompatibility and malleability attributes. These advantageous properties often facilitate natural cell infiltration and tissue reconstruction for regenerative medicine. Due to their excellent fluidity, the injectable hydrogels can be administered in a liquid state and subsequently formed into a gel state in vivo, stabilising the target area and serving in a variety of ways, such as support, repair, and drug release functions. Thus, dECM-based injectable hydrogels have broad prospects for application in complex organ structures and various tissue injury models. This review focuses on exploring research advances in dECM-based injectable hydrogels, primarily focusing on the applications and prospects of dECM hydrogels in tissue engineering. Initially, the recent developments of the dECM-based injectable hydrogels are explained, summarising the different preparation methods with the evaluation of injectable hydrogel properties. Furthermore, some specific examples of the applicability of dECM-based injectable hydrogels are presented. Finally, we summarise the article with interesting prospects and challenges of dECM-based injectable hydrogels, providing insights into the development of these composites in tissue engineering and regenerative medicine.

High microvessel and lymphatic vessel density predict poor prognosis in patients with esophageal squamous cell carcinoma.

Background: Microangiogenesis and lymphangiogenesis are essential for tumor growth in the tumor microenvironment, contributing to tumor invasion and metastasis. Limited literature exists on these processes in esophageal squamous cell carcinoma (ESCC). Therefore, the purpose of this study is to explore the impacts of microangiogenesis and lymphangiogenesis on the occurrence, progression, and prognosis assessment of ESCC. Methods: Surgical specimens and paraffin-embedded human tissues were procured from ESCC patients, encompassing 100 ESCC tissues and 100 cancer-adjacent normal (CAN) tissues. CD34 and D2-40 were utilized as markers for microvessel endothelial cells and lymphatic vessel endothelial cells, respectively. Microvascular density (MVD) and lymphatic vessel density (LVD) were evaluated through immunohistochemical quantification. Results: We found that tumor tissues in ESCC patients had significantly higher MVD and LVD than cancer-adjacent normal (CAN) tissues. High MVD and LVD were associated with lymph node metastasis and advanced tumor clinical stages. Additionally, both high MVD and high LVD were strongly linked to poorer prognosis among cancer patients. Furthermore, a positive correlation was found between high MVD and high LVD (p < 0.05). The presence of these markers individually indicated a worse prognosis, with their combined assessment showcasing enhanced prognostic value. Conclusions: Overall, the increased MVD and LVD indicates higher invasion and metastasis of ESCC, closely correlating with unfavorablefor poor prognosis of ESCC patients.

Chronic hypoxia drives the occurrence of ferroptosis in liver of fat greening (Hexagrammos otakii) by activating HIF-1α and promoting iron production.

BACKGROUND: Hypoxia caused by global climate change and human activities has become a growing concern eliciting serious effect and damages to aquatic animals. Hexagrammos otakii is usually a victim of hypoxia which caused by high density aquaculture and high nutrient input. The mechanism underlying ferroptosis regulation after hypoxia-stress in liver of H. otakii, however, remains elusive. METHODS: For a duration of 15 days, expose the H. otakii to low concentrations of dissolved oxygen (3.4 ± 0.2 mg/L). Detecting alterations in the H. otakii liver tissue by chemical staining, immunohistochemistry, and electron microscopy. The expression variations of relevant genes in the liver of the H. otakii were simultaneously detected using Western blot and qPCR. A correlation analysis was performed between HIF-1α and iron ion expression in the liver of H. otakii following hypoxic stress. RESULTS: In this study, we conducted the whole ferroptosis integrated analysis of H. otakii under chronic hypoxic condition. Reactive oxygen species (ROS) are highly accumulated under the hypoxia treatment (Superoxide Dismutase, SOD; Catalase, CAT), and which results in a significantly enhanced of lipid peroxidation (Lipid Peroxidation, LPO; Malondialdehyde, MDA; Aminotransferase, AST; Alanine aminotransferase, ALT) in liver tissue. The HIF-1α signaling is activated to cope with the hypoxia stress through strategies including changing iron ion concentration (Fe3+ and TFR1) to breaking the oxidation balance (GSH and GSH-Px), and enhancing ferroptosis gene expression (GPX4). The expression of genes related to ferroptosis pathway (DMT1, FTH1, STEAP3, ACSL4, γ-GCS, SLC7A11) is significantly upregulated and associated to the expression of iron and HIF-1α. CONCLUSIONS: It is demonstrated that the HIF-1α/Fe3+/ROS/GPX4 axis is involved in promoting ferroptosis in fat greening hepatocytes following hypoxia-stress. Ultimately, our findings unveil a process by which hypoxic stress strongly encourages ferroptosis by triggering HIF-1α and boosting iron synthesis.