Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study.

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. METHODS: A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP). RESULTS: Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001). CONCLUSIONS: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.

AURKB promotes colorectal cancer progression by triggering the phosphorylation of histone H3 at serine 10 to activate CCNE1 expression.

Aurora kinase B (AURKB) initiates the phosphorylation of serine 10 on histone H3 (pH3S10), a crucial process for chromosome condensation and cytokinesis in mammalian mitosis. Nonetheless, the precise mechanisms through which AURKB regulates the cell cycle and contributes to tumorigenesis as an oncogenic factor in colorectal cancer (CRC) remain unclear. Here, we report that AURKB was highly expressed and positively correlated with Ki-67 expression in CRC. The abundant expression of AURKB promotes the growth of CRC cells and xenograft tumors in animal model. AURKB knockdown substantially suppressed CRC proliferation and triggered cell cycle arrest in G2/M phase. Interestingly, cyclin E1 (CCNE1) was discovered as a direct downstream target of AURKB and functioned synergistically with AURKB to promote CRC cell proliferation. Mechanically, AURKB activated CCNE1 expression by triggering pH3S10 in the promoter region of CCNE1. Furthermore, it was showed that the inhibitor specific for AURKB (AZD1152) can suppress CCNE1 expression in CRC cells and inhibit tumor cell growth. To conclude, this research demonstrates that AURKB accelerated the tumorigenesis of CRC through its potential to epigenetically activate CCNE1 expression, suggesting AURKB as a promising therapeutic target in CRC.

Atypical connectome topography and signal flow in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common pharmaco-resistant epilepsy in adults. While primarily associated with mesiotemporal pathology, recent evidence suggests that brain alterations in TLE extend beyond the paralimbic epicenter and impact macroscale function and cognitive functions, particularly memory. Using connectome-wide manifold learning and generative models of effective connectivity, we examined functional topography and directional signal flow patterns between large-scale neural circuits in TLE at rest. Studying a multisite cohort of 95 patients with TLE and 95 healthy controls, we observed atypical functional topographies in the former group, characterized by reduced differentiation between sensory and transmodal association cortices, with most marked effects in bilateral temporo-limbic and ventromedial prefrontal cortices. These findings were consistent across all study sites, present in left and right lateralized patients, and validated in a subgroup of patients with histopathological validation of mesiotemporal sclerosis and post-surgical seizure freedom. Moreover, they were replicated in an independent cohort of 30 TLE patients and 40 healthy controls. Further analyses demonstrated that reduced differentiation related to decreased functional signal flow into and out of temporolimbic cortical systems and other brain networks. Parallel analyses of structural and diffusion-weighted MRI data revealed that topographic alterations were independent of TLE-related cortical thinning but partially mediated by white matter microstructural changes that radiated away from paralimbic circuits. Finally, we found a strong association between the degree of functional alterations and behavioral markers of memory dysfunction. Our work illustrates the complex landscape of macroscale functional imbalances in TLE, which can serve as intermediate markers bridging microstructural changes and cognitive impairment.

Cellular senescence in cancer: molecular mechanisms and therapeutic targets.

Aging exhibits several hallmarks in common with cancer, such as cellular senescence, dysbiosis, inflammation, genomic instability, and epigenetic changes. In recent decades, research into the role of cellular senescence on tumor progression has received widespread attention. While how senescence limits the course of cancer is well established, senescence has also been found to promote certain malignant phenotypes. The tumor-promoting effect of senescence is mainly elicited by a senescence-associated secretory phenotype, which facilitates the interaction of senescent tumor cells with their surroundings. Targeting senescent cells therefore offers a promising technique for cancer therapy. Drugs that pharmacologically restore the normal function of senescent cells or eliminate them would assist in reestablishing homeostasis of cell signaling. Here, we describe cell senescence, its occurrence, phenotype, and impact on tumor biology. A "one-two-punch" therapeutic strategy in which cancer cell senescence is first induced, followed by the use of senotherapeutics for eliminating the senescent cells is introduced. The advances in the application of senotherapeutics for targeting senescent cells to assist cancer treatment are outlined, with an emphasis on drug categories, and the strategies for their screening, design, and efficient targeting. This work will foster a thorough comprehension and encourage additional research within this field.

Observation and quantification of the pseudogap in unitary Fermi gases.

The microscopic origin of high-temperature superconductivity in cuprates remains unknown. It is widely believed that substantial progress could be achieved by better understanding of the pseudogap phase, a normal non-superconducting state of cuprates1,2. In particular, a central issue is whether the pseudogap could originate from strong pairing fluctuations3. Unitary Fermi gases4,5, in which the pseudogap-if it exists-necessarily arises from many-body pairing, offer ideal quantum simulators to address this question. Here we report the observation of a pair-fluctuation-driven pseudogap in homogeneous unitary Fermi gases of lithium-6 atoms, by precisely measuring the fermion spectral function through momentum-resolved microwave spectroscopy and without spurious effects from final-state interactions. The temperature dependence of the pairing gap, inverse pair lifetime and single-particle scattering rate are quantitatively determined by analysing the spectra. We find a large pseudogap above the superfluid transition temperature. The inverse pair lifetime exhibits a thermally activated exponential behaviour, uncovering the microscopic virtual pair breaking and recombination mechanism. The obtained large, temperature-independent single-particle scattering rate is comparable with that set by the Planckian limit6. Our findings quantitatively characterize the pseudogap in strongly interacting Fermi gases and they lend support for the role of preformed pairing as a precursor to superfluidity.

How to rationally design homogeneous catalysts for efficient CO2 electroreduction?

Electrified converting CO2 into valuable fuels and chemicals using a homogeneous electrochemical CO2 reduction (CO2ER) approach simplifies the operation, providing a potential option for decoupling energy harvesting and renewable chemical production. These merits benefit the scenarios where decentralization and intermittent power are key factors. This perspective aims to provide an overview of recent progress in homogeneous CO2ER. We introduce firstly the fundamentals chemistry of the homogeneous CO2ER, followed by a summary of the crucial factors and the important criteria broadly employed for evaluating the performance. We then highlight the recent advances in the most widely explored transition-metal coordinate complexes for the C1 and multicarbon (C2+) products from homogeneous CO2ER. Finally, we summarize the remaining challenges and opportunities for developing homogeneous electrocatalysts for efficient CO2ER. This perspective is expected to favor the rational design of efficient homogeneous electrocatalysts for selective CO2ER toward renewable fuels and feedstocks.

Delay-dependent Lurie-Postnikov type Lyapunov-Krasovskii functionals for stability analysis of discrete-time delayed neural networks.

This paper addresses the influence of time-varying delay and nonlinear activation functions with sector restrictions on the stability of discrete-time neural networks. Compared to previous works that mainly focuses on the influence of delay information, this paper devotes to activation nonlinear functions information to help compensate the analysis technique based on Lyapunov-Krasovskii functional (LKF). A class of delay-dependent Lurie-Postnikov type integral terms involving sector constraints of nonlinear activation function is proposed to complement the LKF construction. The less conservative criteria for the stability analysis of discrete-time delayed networks is given by using improved LKF. Numerical examples show that conservatism can be reduced by the delay-dependent integral terms involving nonlinear activation functions.

Reduction of 5-Hydroxymethylfurfural to 2,5-Bis(hydroxymethyl)Furan at High Current Density using a Ga-Doped AgCu:Cationomer Hybrid Electrocatalyst.

Hydrogenation of biomass-derived chemicals is of interest for the production of biofuels and valorized chemicals. Thermochemical processes for biomass reduction typically employ hydrogen as the reductant at elevated temperatures and pressures. Here, the authors investigate the direct electrified reduction of 5-hydroxymethylfurfural (HMF) to a precursor to bio-polymers, 2,5-bis(hydroxymethyl)furan (BHMF). Noting a limited current density in prior reports of this transformation, a hybrid catalyst consisting of ternary metal nanodendrites mixed with a cationic ionomer, the latter purposed to increase local pH and facilitate surface proton diffusion, is investigated. This approach, when implemented using Ga-doped Ag-Cu electrocatalysts designed for p-d orbital hybridization, steered selectivity to BHMF, achieving a faradaic efficiency (FE) of 58% at 100 mA cm-2 and a production rate of 1 mmol cm-2 h-1, the latter a doubling in rate compared to the best prior reports.

A Degree-Dependent Polynomial-Based Reciprocally Convex Matrix Inequality and Its Application to Stability Analysis of Delayed Neural Networks.

In this article, several improved stability criteria for time-varying delayed neural networks (DNNs) are proposed. A degree-dependent polynomial-based reciprocally convex matrix inequality (RCMI) is proposed for obtaining less conservative stability criteria. Unlike previous RCMIs, the matrix inequality in this article produces a polynomial of any degree in the time-varying delay, which helps to reduce conservatism. In addition, to reduce the computational complexity caused by dealing with the negative definite of the high-degree terms, an improved lemma is presented. Applying the above matrix inequalities and improved negative definiteness condition helps to generate a more relaxed stability criterion for analyzing time-varying DNNs. Two examples are provided to illustrate this statement.

Unveiling CRESS DNA Virus Diversity in Oysters by Virome.

Oysters that filter feed can accumulate numerous pathogens, including viruses, which can serve as a valuable viral repository. As oyster farming becomes more prevalent, concerns are mounting about diseases that can harm both cultivated and wild oysters. Unfortunately, there is a lack of research on the viruses and other factors that can cause illness in shellfish. This means that it is harder to find ways to prevent these diseases and protect the oysters. This is part of a previously started project, the Dataset of Oyster Virome, in which we further study 30 almost complete genomes of oyster-associated CRESS DNA viruses. The replication-associated proteins and capsid proteins found in CRESS DNA viruses display varying evolutionary rates and frequently undergo recombination. Additionally, some CRESS DNA viruses have the capability for cross-species transmission. A plethora of unclassified CRESS DNA viruses are detectable in transcriptome libraries, exhibiting higher levels of transcriptional activity than those found in metagenome libraries. The study significantly enhances our understanding of the diversity of oyster-associated CRESS DNA viruses, emphasizing the widespread presence of CRESS DNA viruses in the natural environment and the substantial portion of CRESS DNA viruses that remain unidentified. This study's findings provide a basis for further research on the biological and ecological roles of viruses in oysters and their environment.

Identifying individual's distractor suppression using functional connectivity between anatomical large-scale brain regions.

Distractor suppression (DS) is crucial in goal-oriented behaviors, referring to the ability to suppress irrelevant information. Current evidence points to the prefrontal cortex as an origin region of DS, while subcortical, occipital, and temporal regions are also implicated. The present study aimed to examine the contribution of communications between these brain regions to visual DS. To do it, we recruited two independent cohorts of participants for the study. One cohort participated in a visual search experiment where a salient distractor triggering distractor suppression to measure their DS and the other cohort filled out a Cognitive Failure Questionnaire to assess distractibility in daily life. Both cohorts collected resting-state functional magnetic resonance imaging (rs-fMRI) data to investigate function connectivity (FC) underlying DS. First, we generated predictive models of the DS measured in visual search task using resting-state functional connectivity between large anatomical regions. It turned out that the models could successfully predict individual's DS, indicated by a significant correlation between the actual and predicted DS (r = 0.32, p < 0.01). Importantly, Prefrontal-Temporal, Insula-Limbic and Parietal-Occipital connections contributed to the prediction model. Furthermore, the model could also predict individual's daily distractibility in the other independent cohort (r = -0.34, p < 0.05). Our findings showed the efficiency of the predictive models of distractor suppression encompassing connections between large anatomical regions and highlighted the importance of the communications between attention-related and visual information processing regions in distractor suppression. Current findings may potentially provide neurobiological markers of visual distractor suppression.

Progranulin promotes regulatory T cells plasticity by mitochondrial metabolism through AMPK/PGC-1α pathway in ARDS.

As the aging population increases, the focus on elderly patients with acute respiratory distress syndrome (ARDS) is also increasing. In this article, we found progranulin (PGRN) differential expression in ARDS patients and healthy controls, even in young and old ARDS patients. Its expression strongly correlates with several cytokines in both young and elderly ARDS patients. PGRN has comparable therapeutic effects in young and elderly mice with lipopolysaccharide-induced acute lung injury, manifesting as lung injury, apoptosis, inflammation, and regulatory T cells (Tregs) differentiation. Considering that Tregs differentiation relies on metabolic reprogramming, we discovered that Tregs differentiation was mediated by mitochondrial function, especially in the aged population. Furthermore, we demonstrated that PGRN alleviated the mitochondrial damage during Tregs differentiation through the AMPK/PGC-1α pathway in T cells. Collectively, PGRN may regulate mitochondria function to promote Tregs differentiation through the AMPK/PGC-1α pathway to improve ARDS.

Oral compound probiotic supplements can improve the quality of life for patients with lung cancer during chemotherapy: A randomized placebo-controlled study.

BACKGROUND: Chemotherapy is an important approach for lung cancer patients. The study was designed to evaluate the feasibility of the compound probiotic supplements in improving the quality of life for lung cancer patients undergoing chemotherapy. METHODS: This randomized, double-blind, placebo-controlled trial enrolled chemotherapy-naive patients with lung cancer who were scheduled to receive platinum-based doublet chemotherapy. All eligible patients were randomly administered (1:1) compound probiotic supplements (group BP-1) or placebo (group C) for two chemotherapy cycles. The EORTC QLQ C30 questionnaire scores were evaluated before the first, second, and third cycles of chemotherapy. The primary endpoint was the difference in the EROTC QLQ C30 questionnaire score between the two groups after two cycles of chemotherapy. RESULTS: A total of 110 patients were recruited from March 2021 to January 2022. After undergoing two cycles of chemotherapy, group BP-1 were significantly better in various dimensions of the overall quality of life, role function, nausea and vomiting, appetite loss, constipation, and diarrhea relative to group C (76.90 ± 18.31 vs. 58.89 ± 17.17; 93.33 ± 11.58 vs. 85.93 ± 15.06; 0.00 ± 0.00 vs. 27.04 ± 29.15; 6.67 ± 13.53 vs. 22.22 ± 18.80; 0.95 ± 5.63 vs. 28.15 ± 22.42; 2.86 ± 9.47 vs. 15.56 ± 16.82; p < 0.05, respectively). The incidence of nausea and vomiting, appetite loss, constipation, and diarrhea in group BP-1 was significantly lower than in group C (0% vs. 71.43%, 16.67% vs. 57.14%, 2.38% vs. 63.27%, and 7.14% vs. 42.86%, respectively, p < 0.001). CONCLUSIONS: Compound probiotic supplements can improve the quality of life and relieve chemotherapy-related gastrointestinal side effects for lung cancer patients receiving platinum-based doublet chemotherapy. (Chinese Clinical Trial Registry: ChiCTR1800019269).

Exploring the catalytic diversity of two short-chain dehydrogenases/reductases from Stachybotrys chartarum.

Short-chain dehydrogenase/reductases (SDRs) belong to the NAD(P)(H)-dependent oxidoreductase superfamily, which have various functions of catalyzing oxidation/reduction reactions and have been generally used as powerful biocatalysts in the production of pharmaceuticals. In this study, ScSDR1 and ScSDR2, two new SDRs have been identified and characterized from Stachybotrys chartarum 3.5365. Substrate scope investigation revealed that both of the enzymes possessed the ability to oxidize ß-OH to ketone specifically, and exhibited substrate promiscuity and high stereo-selectivity for efficiently catalyzing the structurally different prochiral ketones to chiral alcohols. These findings not only suggest that ScSDR1 and ScSDR2 might be potent synthetic tools in drug research and development, but also provide good examples for further engineered enzymes with higher efficiency and stereo-selectivity.

Pd Decoration with Synergistic High Oxygen Mobility Boosts Hydrogen Sensing Performance at Low Working Temperature on WO3 Nanosheet.

Pd-based materials have received remarkable attention and exhibit excellent H2 sensing performance due to their superior hydrogen storage and catalysis behavior. However, the synergistic effects originated from the decoration of Pd on a metal oxide support to boost the sensing performance are ambiguous, and the deep investigation of metal support interaction (MSI) on the H2 sensing mechanism is still unclear. Here, the model material of Pd nanoparticle-decorated WO3 nanosheet is synthesized, and individual fine structures can be achieved by treating it at different temperatures. Notably, the Pd-WO3-300 materials display superior H2 sensing performance at a low working temperature (110 °C), with a superior sensing response (Ra/Rg = 40.63 to 10 ppm), high sensing selectivity, and anti-interference ability. DFT calculations and detailed structural investigations confirm that the moderate MSI facilitates the generation of high mobility surface O2- (ad) species and a proper ratio of surface Pd0-Pd2+ species, which can significantly boost the desorption of intermediate PdHx species at low temperatures and contribute to enhanced sensing performance. Our work illustrates the effect of MSI on sensing performance and provides insight into the design of advanced sensing materials.

Asymmetric Friedel-Crafts reaction of unsaturated carbonyl-tethered heteroarenes via vinylogous activation of Pd0-π-Lewis base catalysis.

The alkyne group can undergo facile transformations under palladium catalysis, such as hydropalladation, Wacker reaction, etc. Here we demonstrate that a chiral Pd0 complex can chemoselectively dihapto-coordinate to the alkyne moiety of 2-indolyl propiolates, and raise the Highest Occupied Molecular Orbital (HOMO)-energy ofthe deactivated heteroarenes via π-Lewis base catalysis. As a result, asymmetric C3-selective Friedel-Crafts addition to activated alkenes occurs, finally affording [3 + 2] or [3 + 4] annulation products with high enantioselectivity and exclusive E-selectivity. Moreover, this π-Lewis base vinylogous HOMO-activation strategy can be extended to remote Friedel-Crafts reaction of diverse five-membered heteroarenes tethered to a 2-enone or 2-acrylate motif with imines or 1-azadienes, and excellent enantiocontrol is generally achieved for the multifunctional adducts, which can be effectively converted to diverse frameworks with higher molecular complexity. In addition, NMR and density functional theory calculation studies are conducted to elucidate the catalytic mechanism.

Photothermal-Starvation Therapy Nanomodulator Capable of Inhibiting Colorectal Cancer Recurrence and Metastasis by Energy Metabolism Reduction.

The recurrence and metastasis of colorectal cancer (CRC) have been considered as a severe challenge in clinical treatment. Recent studies have demonstrated that matrix metalloproteinases (MMPs) and lactate can promote local tumor angiogenesis, recurrence, and metastasis. The expression of MMPs is highly dependent on energy metabolism, and lactate is considered an alternative energy source for tumor proliferation and metastasis. Therefore, using a rational approach, a photothermal-starvation therapy nanomodulator that can reduce energy metabolism to suppress CRC recurrence and metastasis is designed. To design a suitable nanomodulator, glucose oxidase (GOX), indocyanine green (IR820), and α-cyano-4-hydroxycinnamic acid (CHC) into nanoparticles by a coassembly method are combined. The photothermal properties of IR820 provide the appropriate temperature and oxygen supply for the enzymatic reaction of GOX to promote intracellular glucose consumption. CHC inhibits the expression of monocarboxylate transporter 1 (MCT1), the transporter of lactic acid into cells, and also reduces oxygen consumption and promotes the GOX reaction. Additionally, altering adenosine triphosphate synthesis to block heat shock proteins expression can be an effective means to prevent IR820-mediated photothermal therapy resistance. Thus, this dual photothermal-starvation therapy nanomodulator efficiently suppresses the recurrence and metastasis of CRC by depleting intracellular nutrients.

Analysis of the Promoter Regions of gga-miR-31 and Its Regulation by RA and C-jun in Chicken.

The role of gga-miR-31 in chicken germ cell differentiation and spermatogenesis is of significant importance. The transcriptional properties of gga-miR-31 are crucial in establishing the foundation for the formation of chicken spermatogonia stem cells and spermatogenesis. In this study, a series of recombinant vectors including varying lengths of the gga-miR-31 promoter were predicted and constructed. Through the utilization of the dual luciferase reporting system, the upstream -2180~0 bp region of gga-miR-31 was identified as its promoter region. Furthermore, it was predicted and confirmed that the activity of the gga-miR-31 promoter is increased by retinoic acid (RA). The binding of RA to the gga-miR-31 and Stra8 promoter regions was found to be competitive. Through the deletion of C-jun binding sites and the manipulation of C-jun expression levels, it was determined that C-jun inhibits the activity of the gga-miR-31 promoter. Furthermore, the combined treatment of C-jun and RA demonstrated that the positive regulatory effect of RA on the gga-miR-31 promoter is attenuated in the presence of high levels of C-jun. Overall, this study establishes a foundation for further investigation into the regulatory mechanisms of gga-miR-31 action, and provides a new avenue for inducing chicken embryonic stem cells (ESC) to differentiate into spermatogonial stem cells (SSC), and sperm formation.

ZmMS1/ZmLBD30-orchestrated transcriptional regulatory networks precisely control pollen exine development.

Because of its significance for plant male fertility and, hence, direct impact on crop yield, pollen exine development has inspired decades of scientific inquiry. However, the molecular mechanism underlying exine formation and thickness remains elusive. In this study, we identified that a previously unrecognized repressor, ZmMS1/ZmLBD30, controls proper pollen exine development in maize. Using an ms1 mutant with aberrantly thickened exine, we cloned a male-sterility gene, ZmMs1, which encodes a tapetum-specific lateral organ boundary domain transcription factor, ZmLBD30. We showed that ZmMs1/ZmLBD30 is initially turned on by a transcriptional activation cascade of ZmbHLH51-ZmMYB84-ZmMS7, and then it serves as a repressor to shut down this cascade via feedback repression to ensure timely tapetal degeneration and proper level of exine. This activation-feedback repression loop regulating male fertility is conserved in maize and sorghum, and similar regulatory mechanism may also exist in other flowering plants such as rice and Arabidopsis. Collectively, these findings reveal a novel regulatory mechanism of pollen exine development by which a long-sought master repressor of upstream activators prevents excessive exine formation.

Exosomes derived from M2-type microglia ameliorate oxygen-glucose deprivation/reoxygenation-induced HT22 cell injury by regulating miR-124-3p/NCOA4-mediated ferroptosis.

Background: Although it has been reported that miRNA carried by M2 microglial exosomes protects neurons from ischemia-reperfusion brain injury, the mechanism of action remains poorly understood. This study aimed to explore the miRNA signaling pathway by which M2-type microglia-derived exosomes (M2-exosomes) ameliorate oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cytotoxicity in HT22 cells. Methods: BV2 microglia were induced by M2 polarization. Then, M2-exosomes were identified via transmission electron microscopy and special biomarker detection and co-cultured with HT22 cells. Cell proliferation was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Intracellular concentrations of reactive oxygen species (ROS), Fe2+, glutathione (GSH), and malondialdehyde (MDA) were determined using dichlorofluorescein fluorescence and biochemical determination. miR-124-3p levels were determined using qRT-PCR, and protein expressions were examined via western blotting. Results: OGD/R suppressed the proliferation and induced the accumulation of Fe2+, ROS, and MDA and reduction of GSH in mouse HT22 cells, suggesting ferroptosis of HT22 cells. OGD/R-induced changes in the above mentioned indexes was ameliorated by M2-exosomes but restored by the exosome inhibitor GW4869. M2-exosomes with (mimic-exo) or without miR-124-3p (inhibitor-exo) promoted and suppressed proliferation and ferroptosis-associated indexes of HT22 cells, respectively. Moreover, mimic-exo and inhibitor-exo inhibited and enhanced NCOA4 expression in HT22 cells, respectively. NCOA4 overexpression reversed the protective effects of miR-124-3p mimic-exo in OGD/R-conditioned cells. NCOA4 was targeted and regulated by miR-124-3p. Conclusions: M2-exosome protects HT22 cells against OGD/R-induced ferroptosis injury by transferring miR-124-3p and NCOA4 into HT22 cells, with the latter being a target gene for miR-124-3p.