Inhibition of ATP1V6G3 prompts hepatic stellate cell senescence with reducing ECM by activating Notch1 pathway to alleviate hepatic fibrosis.

Liver fibrosis is characterized by an excessive reparative response to various etiological factors, with the activated hepatic stellate cells (aHSCs) leading to extracellular matrix (ECM) accumulation. Senescence is a stable growth arrest, and the senescence of aHSCs is associated with the degradation of ECM and the regression of hepatic fibrosis, making it a promising approach for managing hepatic fibrosis. The role and specific mechanisms by which V-Type Proton ATPase Subunit G 3 (ATP6V1G3) influences senescence in activated HSCs during liver fibrosis remain unclear. Our preliminary results reveal upregulation of ATP6V1G3 in both human fibrotic livers and murine liver fibrosis models. Additionally, ATP6V1G3 inhibition induced senescence in aHSCs in vitro. Moreover, suppressing Notch1 reversed the senescence caused by ATP6V1G3 inhibition in HSCs. Thus, targeting ATP6V1G3, which appears to drive HSCs senescence through the Notch1 pathway, emerges as a potential therapeutic strategy for hepatic fibrosis.

Study on the chemical composition of Gegen-Tianma decoction and its absorbed constituents in rat plasma, brain based on UPLC-Q-TOF-MS and DESI-MSI.

In traditional Chinese medicinal practices, Gegen (GG) and Tianma (TM) are widely utilized for headache relief, but their material basis has not been comprehensively characterized. This research utilized ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) for precise determination of Gegen-Tianma's (GGTM) material composition, and employed desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) to pinpoint the brain-absorbed components and various metabolites post oral administration to rats. A total of 80 chemical constituents were identified from GGTM, 11 prototypes and 18 metabolites were identified from plasma. The brain tissue was identified in total 4 prototypes and 5 metabolites, these constituents were basically located in the prefrontal cortex and thalamus. The absorption patterns of components in the rat brain aligned with the varied distribution of metabolites within the brain. This study provides a solid theoretical basis for in-depth exploration of potential drug targets and elucidation of the specific mechanism of action of GGTM in the treatment of migraine.

SMARCA4-deficient undifferentiated tumor with high quality of life and far exceeding predicted survival: A case report.

RATIONALE: SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently reported rare malignancy that can rapidly metastasize to tissues and organs throughout the body. The tumor is characterized by a lower response to platinum-based chemotherapy. More regrettably, the mean survival time of patients with this disease after diagnosis is only 4 to 7 months. PATIENT CONCERNS: A 58-year-old man was admitted to a hospital for fatigue, sudden syncope, and a mass-like shadow of his left upper lobe demonstrated by a pulmonary computed tomographic. Based on his subsequent clinical and pathological features, he was highly suspected of SMARCA4-UT. DIAGNOSES: Combined with next-generation sequencing genetic testing and immunohistochemical examination results, the patient was diagnosed with SMARCA4-UT. INTERVENTIONS: The patient received a left upper lobectomy and lymph node dissection, four-course chemotherapy divided into 8 sessions with the use of paclitaxel simply, and a proper post-discharge self-care. OUTCOMES: The patient's operation and chemotherapy were all successful and he maintained a high quality of life after surgery that far exceeded his predicted survival. LESSONS: Early diagnosis, higher education level, attention to the disease and complications, reducing chemotherapy damage, adequate nutrient intake, relieving symptoms, controlling depression, and maintaining immunity and the ability to perform activities of daily living may all be the positive factors that can prolong the survival of patients with SMARCA4-UT.

Potential dynamic corneal response parameters for myopia: relationships between axial length with whole eye movement at the first and second applanations and the highest concavity.

PURPOSE: To investigate the correlation between whole eye movement (WEM) parameters measured using Corvis ST and axial length (AL) to explore whether AL affects WEMs. METHODS: This single-center, cross-sectional study included data from healthy subjects and patients preparing for refractive surgery at the Qingdao Eye Hospital of Shandong First Medical University. Data were collected from July 2021 to April 2022. We first determined the correlations of WEMs at the time of corneal first applanation (A1_WEM), highest concavity (HC_WEM), and second applanation (A2_WEM), as well as the maximum value of WEM (WEM_Max) with AL. Subsequently, we established a series of regression models to analyze the relationships between different WEM values and AL. RESULTS: AL was negatively correlated with HC_WEM, A2_WEM, and WEM_Max (r = - 0.28, - 0.23, and - 0.22, respectively; P < 0.001). The correlation between AL and A1_WEM was not significant (P = 0.77). According to the adjusted regression models, AL was negatively associated with HC_WEM (Model 2: ß = -7.39, P < 0.001) and WEM_Max (Model 4: ß = -3.52, P = 0.02), while the associations of AL with A1_WEM (Model 1: P = 0.61) and A2_WEM (Model 3: P = 0.23) were not significant. CONCLUSIONS: AL is an independent negative influencing factor for HC_WEM. WEM is a potentially useful parameter that reflects the biomechanical properties of the eye behind the cornea in myopia.

The Restriction Activity Investigation of Rv2528c, an Mrr-like Modification-Dependent Restriction Endonuclease from Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb), as a typical intracellular pathogen, possesses several putative restriction-modification (R-M) systems, which restrict exogenous DNA's entry, such as bacterial phage infection. Here, we investigate Rv2528c, a putative Mrr-like type IV restriction endonuclease (REase) from Mtb H37Rv, which is predicted to degrade methylated DNA that contains m6A, m5C, etc. Rv2528c shows significant cytotoxicity after being expressed in Escherichia coli BL21(DE3)pLysS strain. The Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay indicates that Rv2528c cleaves genomic DNA in vivo. The plasmid transformation efficiency of BL21(DE3)pLysS strain harboring Rv2528c gene was obviously decreased after plasmids were in vitro methylated by commercial DNA methyltransferases such as M.EcoGII, M.HhaI, etc. These results are consistent with the characteristics of type IV REases. The in vitro DNA cleavage condition and the consensus cleavage/recognition site of Rv2528c still remain unclear, similar to that of most Mrr-family proteins. The possible reasons mentioned above and the potential role of Rv2528c for Mtb were discussed.

Construction of a Risk Prediction Model for the Occurrence of Acute Skin Failure in Critically Ill Patients: A Prospective Study.

BACKGROUND: The risk factors for acute skin failure (ASF), a serious complication of the skin, are not fully understood. PURPOSE: This study was designed to explore the risk factors for ASF in critically ill patients and construct a clinical prediction model. METHODS: Intensive care unit patients were prospectively observed and assigned into two groups: with and without ASF. A logistic regression model was constructed, and its predictive power and clinical utility were evaluated. RESULTS: Of the 204 eligible patients enrolled as participants, 58 (28.43%) developed ASF. Sepsis, vasoactive drugs, and age were shown to be risk factors for ASF, whereas peripheral perfusion index ratio and albumin level were shown to be protective factors. The area under the receiver operating characteristic curve was 0.83. The maximum Youden index of the model was 0.39 (specificity: 0.87, sensitivity: 0.77). The Hosmer-Lemeshow test (p = .20) and calibration curve showed good fitness and predictive utility with respect to the model. CONCLUSIONS: The developed model effectively predicts ASF risk, allowing for the early identification of high-risk patients. Identifying risk factors such as sepsis, vasoactive drugs, and age and considering protective factors such as peripheral perfusion index and albumin levels may help optimize care plans. Clinical staff should pay special attention to these factors and their impact on skin health in critically ill patients.

HigA2 (Rv2021c) Is a Transcriptional Regulator with Multiple Regulatory Targets in Mycobacterium tuberculosis.

Toxin-antitoxin (TA) systems are the major mechanism for persister formation in Mycobacterium tuberculosis (Mtb). Previous studies found that HigBA2 (Rv2022c-Rv2021c), a predicted type II TA system of Mtb, could be activated for transcription in response to multiple stresses such as anti-tuberculosis drugs, nutrient starvation, endure hypoxia, acidic pH, etc. In this study, we determined the binding site of HigA2 (Rv2021c), which is located in the coding region of the upstream gene higB2 (Rv2022c), and the conserved recognition motif of HigA2 was characterized via oligonucleotide mutation. Eight binding sites of HigA2 were further found in the Mtb genome according to the conserved motif. RT-PCR showed that HigA2 can regulate the transcription level of all eight of these genes and three adjacent downstream genes. DNA pull-down experiments showed that twelve functional regulators sense external regulatory signals and may regulate the transcription of the HigBA2 system. Of these, Rv0903c, Rv0744c, Rv0474, Rv3124, Rv2603c, and Rv3583c may be involved in the regulation of external stress signals. In general, we identified the downstream target genes and possible upstream regulatory genes of HigA2, which paved the way for the illustration of the persistence establishment mechanism in Mtb.

Transcriptome profiling of fast/glycolytic and slow/oxidative muscle fibers in aging and obesity.

Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.

[Construction and external validation of a risk prediction model for unplanned interruption during continuous renal replacement therapy].

OBJECTIVE: To identify the independent factors of unplanned interruption during continuous renal replacement therapy (CRRT) and construct a risk prediction model, and to verify the clinical application effectiveness of the model. METHODS: A retrospective study was conducted on critically ill adult patients who received CRRT treatment in the intensive care unit (ICU) of Zhejiang Hospital from January 2021 to August 2022 for model construction. According to whether unplanned weaning occurred, the patients were divided into two groups. The potential influencing factors of unplanned CRRT weaning in the two groups were compared. The independent influencing factors of unplanned CRRT weaning were screened by binary Logistic regression and a risk prediction model was constructed. The goodness of fit of the model was verified by a Hosmer-Lemeshow test and its predictive validity was evaluated by receiver operator characteristic curve (ROC curve). Then embed the risk prediction model into the hospital's ICU multifunctional electronic medical record system for severe illness, critically ill patients with CRRT admitted to the ICU of Zhejiang Hospital from November 2022 to October 2023 were prospectively analyzed to verify the model's clinical application effect. RESULTS: (1) Model construction and internal validation: a total of 331 critically ill patients with CRRT were included to be retrospectively analyzed. Among them, there were 238 patients in planned interruption group and 93 patients in unplanned interruption group. Compared with the planned interruption group, the unplanned interruption group was shown as a lower proportion of males (80.6% vs. 91.6%) and a higher proportion of chronic diseases (60.2% vs. 41.6%), poor blood purification catheter function (31.2% vs. 6.3%), as a higher platelet count (PLT) before CRRT initiation [×109/L: 137 (101, 187) vs. 109 (74, 160)], lower level of blood flow rate [mL/min: 120 (120, 150) vs. 150 (140, 180)], higher proportion of using pre-dilution (37.6% vs. 23.5%), higher filtration fraction [23.0% (17.5%, 32.9%) vs. 19.1% (15.7%, 22.6%)], and frequency of blood pump stops [times: 19 (14, 21) vs. 9 (6, 13)], the differences of the above 8 factors between the two groups were statistically significant (all P < 0.05). Binary Logistic regression analysis showed that chronic diseases [odds ratio (OR) = 3.063, 95% confidence interval (95%CI) was 1.200-7.819], blood purification catheter function (OR = 4.429, 95%CI was 1.270-15.451), blood flow rate (OR = 0.928, 95%CI was 0.900-0.957), and frequency of blood pump stops (OR = 1.339, 95%CI was 1.231-1.457) were the independent factors for the unplanned interruption of CRRT (all P < 0.05). These 4 factors were used to construct a risk prediction model, and ROC curve analysis showed that the area under the curve (AUC) predicted by the model was 0.952 (95%CI was 0.930-0.973, P = 0.003 0), with a sensitivity of 88.2%, a specificity of 89.9%, and a maximum value of 1.781 for the Youden index. (2) External validation: prospective inclusion of 110 patients, including 63 planned interruption group and 47 unplanned interruption group. ROC curve analysis showed that the AUC of the risk prediction model was 0.919 (95%CI was 0.870-0.969, P = 0.004 3), with a sensitivity of 91.5%, a specificity of 79.4%, and a maximum value of the Youden index of 1.709. CONCLUSIONS: The risk prediction model for unplanned interruption during CRRT has a high predictive efficiency, allowing for rapid and real-time identification of the high risk patients, thus providing references for preventative nursing.

Petrocodonliboensis (Gesneriaceae), a new species from Guizhou, China.

Petrocodonliboensis Sheng H.Tang & Jia W.Yang is a new species of Gesneriaceae from Guizhou, southwestern China. The new taxon has a pale-yellow corolla and is most similar to P.luteoflorus. However, it differs from the latter by having a urceolate (vs. cannulate) corolla tube, an abaxial corolla lip 0.8-1.1 mm (vs. 2-2.2 mm) long, and filaments 1.5-1.7 mm (vs. ca. 7 mm) long that are straight (vs. S-shaped or geniculate near the middle). The new taxon is assessed as "Data Deficient" (DD) according to the IUCN standards.

Oxytocin ameliorates cognitive impairments by attenuating excitation/inhibition imbalance of neurotransmitters acting on parvalbumin interneurons in a mouse model of sepsis-associated encephalopathy.

Inflammation plays a crucial role in the initiation and progression of sepsis, and it also induces alterations in brain neurotransmission, thereby contributing to the development of sepsis-associated encephalopathy (SAE). Parvalbumin (PV) interneurons are pivotal contributors to cognitive processes in various central dysfunctions including SAE. Oxytocin, known for its ability to augment the firing rate of gamma-aminobutyric acid (GABA)ergic interneurons and directly stimulate inhibitory interneurons to enhance the tonic inhibition of pyramidal neurons, has prompted an investigation into its potential effects on cognitive dysfunction in SAE. In the current study, we administered intranasal oxytocin to the SAE mice induced by lipopolysaccharide (LPS). Behavioral assessments, including open field, Y-maze, and fear conditioning, were used to evaluate cognitive performance. Golgi staining revealed hippocampal synaptic deterioration, local field potential recordings showed weakened gamma oscillations, and immunofluorescence analysis demonstrated decreased PV expression in the cornu ammonis 1 (CA1) region of the hippocampus following LPS treatment, which was alleviated by oxytocin. Furthermore, immunofluorescence staining of PV co-localization with vesicular glutamate transporter 1 or vesicular GABA transporter indicated a balanced excitation/inhibition effect of neurotransmitters on PV interneurons after oxytocin administration in the SAE mice, leading to improved cognitive function. In conclusion, cognitive function improved after oxytocin treatment. The number of PV neurons in the hippocampal CA1 region and the balance of excitatory/inhibitory synaptic transmission on PV interneurons, as well as changes in local field potential gamma oscillations in the hippocampal CA1 region, may represent its specific mechanisms.

Organellophagy regulates cell death:A potential therapeutic target for inflammatory diseases.

BACKGROUND: Dysregulated alterations in organelle structure and function have a significant connection with cell death, as well as the occurrence and development of inflammatory diseases. Maintaining cell viability and inhibiting the release of inflammatory cytokines are essential measures to treat inflammatory diseases. Recently, many studies have showed that autophagy selectively targets dysfunctional organelles, thereby sustaining the functional stability of organelles, alleviating the release of multiple cytokines, and maintaining organismal homeostasis. Organellophagy dysfunction is critically engaged in different kinds of cell death and inflammatory diseases. AIM OF REVIEW: We summarized the current knowledge of organellophagy (e.g., mitophagy, reticulophagy, golgiphagy, lysophagy, pexophagy, nucleophagy, and ribophagy) and the underlying mechanisms by which organellophagy regulates cell death. KEY SCIENTIFIC CONCEPTS OF REVIEW: We outlined the potential role of organellophagy in the modulation of cell fate during the inflammatory response to develop an intervention strategy for the organelle quality control in inflammatory diseases.

Dysregulated dendritic cells in sepsis: functional impairment and regulated cell death.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Studies have indicated that immune dysfunction plays a central role in the pathogenesis of sepsis. Dendritic cells (DCs) play a crucial role in the emergence of immune dysfunction in sepsis. The major manifestations of DCs in the septic state are abnormal functions and depletion in numbers, which are linked to higher mortality and vulnerability to secondary infections in sepsis. Apoptosis is the most widely studied pathway of number reduction in DCs. In the past few years, there has been a surge in studies focusing on regulated cell death (RCD). This emerging field encompasses various forms of cell death, such as necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death (ADCD). Regulation of DC's RCD can serve as a possible therapeutic focus for the treatment of sepsis. Throughout time, numerous tactics have been devised and effectively implemented to improve abnormal immune response during sepsis progression, including modifying the functions of DCs and inhibiting DC cell death. In this review, we provide an overview of the functional impairment and RCD of DCs in septic states. Also, we highlight recent advances in targeting DCs to regulate host immune response following septic challenge.

Diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging parameters and serum tumor markers in rectal carcinoma prognosis.

BACKGROUND: Rectal carcinoma (RC), one of the most common malignancies globally, presents an increasing incidence and mortality year by year, especially among young people, which seriously affects the prognosis and quality of life of patients. At present, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters and serum carbohydrate antigen 19-9 (CA19-9) and CA125 Levels have been used in clinical practice to evaluate the T stage and differentiation of RC. However, the accuracy of these evaluation modalities still needs further research. This study explores the application and value of these methods in evaluating the T stage and differentiation degree of RC. AIM: To analyze the diagnostic performance of DCE-MRI parameters combined with serum tumor markers (TMs) in assessing pathological processes and prognosis of RC patients. METHODS: A retrospective analysis was performed on 104 RC patients treated at Yantai Yuhuangding Hospital from May 2018 to January 2022. Patients were categorized into stages T1, T2, T3, and T4, depending on their T stage and differentiation degree. In addition, they were assigned to low (L group) and moderate-high differentiation (M + H group) groups based on their differentiation degree. The levels of DCE-MRI parameters and serum CA19-9 and CA125 in different groups of patients were compared. In addition, the value of DCE-MRI parameters [volume transfer constant (Ktrans), rate constant (Kep), and extravascular extracellular volume fraction (Ve) in assessing the differentiation and T staging of RC patients was discussed. Furthermore, the usefulness of DCE-MRI parameters combined with serum CA19-9 and CA125 Levels in the evaluation of RC differentiation and T staging was analyzed. RESULTS: Ktrans, Ve, CA19-9 and CA125 were higher in the high-stage group and L group than in the low-stage group and M + H Group, respectively (P < 0.05). The areas under the curve (AUCs) of the Ktran and Ve parameters were 0.638 and 0.694 in the diagnosis of high and low stages, respectively, and 0.672 and 0.725 in diagnosing moderate-high and low differentiation, respectively. The AUC of DCE-MRI parameters (Ktrans + Ve) in the diagnosis of high and low stages was 0.742, and the AUC in diagnosing moderate-high and low differentiation was 0.769. The AUCs of CA19-9 and CA-125 were 0.773 and 0.802 in the diagnosis of high and low stages, respectively, and 0.834 and 0.796 in diagnosing moderate-high and low differentiation, respectively. Then, we combined DCE-MRI (Ktrans + Ve) parameters with CA19-9 and CA-125 and found that the AUC of DCE-MRI parameters plus serum TMs was 0.836 in the diagnosis of high and low stages and 0.946 in the diagnosis of moderate-high and low differentiation. According to the Delong test, the AUC of DCE-MRI parameters plus serum TMs increased significantly compared with serum TMs alone in the diagnosis of T stage and differentiation degree (P < 0.001). CONCLUSION: The levels of the DCE-MRI parameters Ktrans and Ve and the serum TMs CA19-9 and CA125 all increase with increasing T stage and decreasing differentiation degree of RC and can be used as indices to evaluate the differentiation degree of RC in clinical practice. Moreover, the combined evaluation of the above indices has a better effect and more obvious clinical value, providing important guiding importance for clinical condition judgment and treatment selection.

Extracellular cold-inducible RNA-binding protein mediated neuroinflammation and neuronal apoptosis after traumatic brain injury.

Background: Extracellular cold-inducible RNA-binding protein (eCIRP) plays a vital role in the inflammatory response during cerebral ischaemia. However, the potential role and regulatory mechanism of eCIRP in traumatic brain injury (TBI) remain unclear. Here, we explored the effect of eCIRP on the development of TBI using a neural-specific CIRP knockout (KO) mouse model to determine the contribution of eCIRP to TBI-induced neuronal injury and to discover novel therapeutic targets for TBI. Methods: TBI animal models were generated in mice using the fluid percussion injury method. Microglia or neuron lines were subjected to different drug interventions. Histological and functional changes were observed by immunofluorescence and neurobehavioural testing. Apoptosis was examined by a TdT-mediated dUTP nick end labelling assay in vivo or by an annexin-V assay in vitro. Ultrastructural alterations in the cells were examined via electron microscopy. Tissue acetylation alterations were identified by non-labelled quantitative acetylation via proteomics. Protein or mRNA expression in cells and tissues was determined by western blot analysis or real-time quantitative polymerase chain reaction. The levels of inflammatory cytokines and mediators in the serum and supernatants were measured via enzyme-linked immunoassay. Results: There were closely positive correlations between eCIRP and inflammatory mediators, and between eCIRP and TBI markers in human and mouse serum. Neural-specific eCIRP KO decreased hemispheric volume loss and neuronal apoptosis and alleviated glial cell activation and neurological function damage after TBI. In contrast, eCIRP treatment resulted in endoplasmic reticulum disruption and ER stress (ERS)-related death of neurons and enhanced inflammatory mediators by glial cells. Mechanistically, we noted that eCIRP-induced neural apoptosis was associated with the activation of the protein kinase RNA-like ER kinase-activating transcription factor 4 (ATF4)-C/EBP homologous protein signalling pathway, and that eCIRP-induced microglial inflammation was associated with histone H3 acetylation and the α7 nicotinic acetylcholine receptor. Conclusions: These results suggest that TBI obviously enhances the secretion of eCIRP, thereby resulting in neural damage and inflammation in TBI. eCIRP may be a biomarker of TBI that can mediate the apoptosis of neuronal cells through the ERS apoptotic pathway and regulate the inflammatory response of microglia via histone modification.

Nutrient deprivation induces mouse embryonic diapause mediated by Gator1 and Tsc2.

Embryonic diapause is a special reproductive phenomenon in mammals that helps embryos to survive various harsh stresses. However, the mechanisms of embryonic diapause induced by the maternal environment is still unclear. Here, we uncovered that nutrient deficiency in uterine fluid was essential for the induction of mouse embryonic diapause, shown by a decreased concentration of arginine, leucine, isoleucine, lysine, glucose and lactate in the uterine fluid of mice suffering from maternal starvation or ovariectomy. Moreover, mouse blastocysts cultured in a medium with reduced levels of these six components could mimic diapaused blastocysts. Our mechanistic study indicated that amino acid starvation-dependent Gator1 activation and carbohydrate starvation-dependent Tsc2 activation inhibited mTORC1, leading to induction of embryonic diapause. Our study elucidates the essential environmental factors in diapause induction.

Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.