Genetically evaluating the causal role of peripheral immune cells in colorectal cancer: a two-sample Mendelian randomization study.

BACKGROUND: Investigating novel therapeutic strategies for colorectal cancer (CRC) is imperative. However, there is limited research on the use of drugs to target peripheral blood immune cells in this context. To address this gap, we performed a two-sample Mendelian randomization (MR) analysis to identify potential therapeutic targets for CRC. METHODS: We applied two-sample MR to identify the causal relationship between peripheral blood immune cells and CRC. GWAS data were obtained from the IEU OPEN GWAS project. Based on the implications from the MR results, we conducted a comprehensive database search and genetic analysis to explore potential underlying mechanisms. We predicted miRNAs for each gene and employed extensive research for potential therapeutic applications. RESULTS: We have identified causal associations between two peripheral immune cells and colorectal cancer. Activated & resting Treg %CD4 + cell was positively associated with the risks of CRC, while DN (CD4-CD8-) %leukocyte cell exhibited a protective role in tumor progression. NEK7 (NIMA related kinase 7) and LHX9 (LIM homeobox 9) expressed in Treg cells were positively associated with CRC risks and may play a vital role in carcinogenesis. CONCLUSIONS: This study identified causal relationship between peripheral immune cell and CRC. Treg and DN T cells were implicated to own promoting and inhibiting effects on CRC progression respectively. NEK7 and LHX9 in Treg cells were identified as potential biotarget for antitumor therapies.

Superconducting Field-Effect Transistors with PdxTe-Te Intimate Contacts.

Superconducting-based electronic devices have shown great potential for future quantum computing applications. One key building block device is a superconducting field-effect transistor based on a superconductor-semiconductor-superconductor Josephson-junction (JJ) with a gate-tunable semiconducting channel. However, the performance of such devices is highly dependent on the quality of the superconductor to semiconductor interface. In this study, we present an alternative method to obtain a high-quality interface by using intimate contact. We investigate the proximity-induced superconductivity in chiral crystal tellurium (Te) and fabricate a PdxTe-Te-PdxTe JJ with an ambipolar supercurrent that is gate-tunable and exhibits multiple Andreev reflections. The semiconducting two-dimensional Te single crystal is grown hydrothermally and partially converted to superconducting PdxTe by controlled annealing. Our work demonstrates a promising path for realizing controllable superconducting electronic devices with high-quality superconducting interfaces; thus, we can continue to advance the field of quantum computing and other interface-based technologies.

Structure regulation and synchrotron radiation investigation of cathode materials for aqueous Zn-ion batteries.

In view of the advantages of low cost, environmental sustainability, and high safety, aqueous Zn-ion batteries (AZIBs) are widely expected to hold significant promise and increasingly infiltrate various applications in the near future. The development of AZIBs closely relates to the properties of cathode materials, which depend on their structures and corresponding dynamic evolution processes. Synchrotron radiation light sources, with their rich advanced experimental methods, serve as a comprehensive characterization platform capable of elucidating the intricate microstructure of cathode materials for AZIBs. In this review, we initially examine available cathode materials and discuss effective strategies for structural regulation to boost the storage capability of Zn2+. We then explore the synchrotron radiation techniques for investigating the microstructure of the designed materials, particularly through in situ synchrotron radiation techniques that can track the dynamic evolution process of the structures. Finally, the summary and future prospects for the further development of cathode materials of AZIBs and advanced synchrotron radiation techniques are discussed.

Transcutaneous auricular vagus nerve stimulation with task-oriented training improves upper extremity function in patients with subacute stroke: a randomized clinical trial.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising brain stimulation modality in poststroke upper extremity rehabilitation. Although several studies have examined the safety and reliability of taVNS, the mechanisms underlying motor recovery in stroke patients remain unclear. Objectives: This study aimed to investigate the effects of taVNS paired with task-oriented training (TOT) on upper extremity function in patients with subacute stroke and explore the potential underlying mechanisms. Methods: In this double-blinded, randomized, controlled pilot trial, 40 patients with subacute stroke were randomly assigned to two groups: the VNS group (VG), receiving taVNS during TOT, and the Sham group (SG), receiving sham taVNS during TOT. The intervention was delivered 5 days per week for 4 weeks. Upper extremity function was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT). Activities of daily living were measured by the modified Barthel Index (MBI). Motor-evoked potentials (MEPs) were measured to evaluate cortical excitability. Assessments were administered at baseline and post-intervention. Additionally, the immediate effect of taVNS was detected using functional near-infrared spectroscopy (fNIRS) and heart rate variability (HRV) before intervention. Results: The VG showed significant improvements in upper extremity function (FMA-UE, ARAT) and activities of daily living (MBI) compared to the SG at post-intervention. Furthermore, the VG demonstrated a higher rate of elicited ipsilesional MEPs and a shorter latency of MEPs in the contralesional M1. In the VG, improvements in FMA-UE were significantly associated with reduced latency of contralesional MEPs. Additionally, fNIRS revealed increased activation in the contralesional prefrontal cortex and ipsilesional sensorimotor cortex in the VG in contrast to the SG. However, no significant between-group differences were found in HRV. Conclusion: The combination of taVNS with TOT effectively improves upper extremity function in patients with subacute stroke, potentially through modulating the bilateral cortex excitability to facilitate task-specific functional recovery.

Universal Intercalation/Alloying Hybrid Mechanism with -ICOHP Criterion in MAX Toward Steadily Ascending Lithium-Ion Batteries.

Profiting from the unique atomic laminated structure, metallic conductivity, and superior mechanical properties, transition metal carbides and nitrides named MAX phases have shown great potential as anodes in lithium-ion batteries. However, the complexity of MAX configurations poses a challenge. To accelerate such application, a minus integrated crystal orbital Hamilton populations descriptor is innovatively proposed to rapidly evaluate the lithium storage potential of various MAX, along with density functional theory computations. It confirms that surface A-element atoms bound to lithium ions have odds of escaping from MAX. Interestingly, the activated A-element atoms enhance the reversible uptake of lithium ions by MAX anodes through an efficient alloying reaction. As an experimental verification, the charge compensation and SnxLiy phase evolution of designed Zr2SnC MAX with optimized structure is visualized via in situ synchrotron radiation XRD and XAFS technique, which further clarifies the theoretically expected intercalation/alloying hybrid storage mechanism. Notably, Zr2SnC electrodes achieve remarkably 219.8% negative capacity attenuation over 3200 cycles at 1 A g-1. In principle, this work provides a reference for the design and development of advanced MAX electrodes, which is essential to explore diversified applications of the MAX family in specific energy fields.

Anion Additive Integrated Electric Double Layer and Solvation Shell for Aqueous Zinc Ion Battery.

Aqueous zinc ion batteries (AZIBs) show great potential in large-scale energy storage systems. However, the inferior cycling life due to water-induced parasitic reactions and uncontrollable dendrites growth impede their application. Electrolyte optimization via the use of additives is a promising strategy to enhance the stability of AZIBs. Nevertheless, the mechanism of optimal multifunctional additive strategy requires further exploration. Herein, sodium dodecyl benzene sulfonate (SDBS) is proposed as a dual-functional additive in ZnSO4 electrolyte. Benefiting from the additive, both side reactions and zinc dendrites growth are significantly inhibited. Further, a synchrotron radiational spectroscopic study is employed to investigate SDB- adjusted electric double layer (EDL) near the Zn surface and the optimized solvation sheath of Zn2+. First-principles calculations verify the firm adsorption of SDB-, and restriction of random diffusion of Zn2+ on the Zn surface. In particular, the SDBS additive endows Zn||Zn symmetric cells with a 1035 h ultra-stable plating/stripping at 0.2 mA cm-2. This work not only provides a promising design strategy by dual-functional electrolyte additives for high stable AZIBs, but also exhibits the prospect of synchrotron radiation spectroscopy analysis on surface EDL and Zn2+ solvation shell optimization.

URI alleviates tyrosine kinase inhibitors-induced ferroptosis by reprogramming lipid metabolism in p53 wild-type liver cancers.

The clinical benefit of tyrosine kinase inhibitors (TKIs)-based systemic therapy for advanced hepatocellular carcinoma (HCC) is limited due to drug resistance. Here, we uncover that lipid metabolism reprogramming mediated by unconventional prefoldin RPB5 interactor (URI) endows HCC with resistance to TKIs-induced ferroptosis. Mechanistically, URI directly interacts with TRIM28 and promotes p53 ubiquitination and degradation in a TRIM28-MDM2 dependent manner. Importantly, p53 binds to the promoter of stearoyl-CoA desaturase 1 (SCD1) and represses its transcription. High expression of URI is correlated with high level of SCD1 and their synergetic expression predicts poor prognosis and TKIs resistance in HCC. The combination of SCD1 inhibitor aramchol and deuterated sorafenib derivative donafenib displays promising anti-tumor effects in p53-wild type HCC patient-derived organoids and xenografted tumors. This combination therapy has potential clinical benefits for the patients with advanced HCC who have wild-type p53 and high levels of URI/SCD1.

Tunable Chirality-Dependent Nonlinear Electrical Responses in 2D Tellurium.

Tellurium (Te) is an elemental semiconductor with a simple chiral crystal structure. Te in a two-dimensional (2D) form synthesized by a solution-based method shows excellent electrical, optical, and thermal properties. In this work, the chirality of hydrothermally grown 2D Te is identified and analyzed by hot sulfuric acid etching and high-angle tilted high-resolution scanning transmission electron microscopy. The gate-tunable nonlinear electrical responses, including the nonreciprocal electrical transport in the longitudinal direction and the nonlinear planar Hall effect in the transverse direction, are observed in 2D Te under a magnetic field. Moreover, the nonlinear electrical responses have opposite signs in left- and right-handed 2D Te due to the opposite spin polarizations ensured by the chiral symmetry. The fundamental relationship between the spin-orbit coupling and the crystal symmetry in two enantiomers provides a viable platform for realizing chirality-based electronic devices by introducing the degree of freedom of chirality into electron transport.

Safety and efficacy of GEMOX plus donafenib and tislelizumab as first-line therapy for advanced epithelial malignant biliary tract cancer.

AIM: This study was aimed to evaluate the safety and the efficacy of gemcitabine and oxaliplatin (GEMOX) combined with donafenib plus tislelizumab as the first-line treatment for patients with unresectable biliary tract cancer (BTC). METHODS: This is a prospective single-center exploratory study. Eligible patients (Stage III/IV BTC, at least one measurable disease according to RECIST v1.1, etc.) received gemcitabine 1000 mg/m2 IV Q3W, oxaliplatin 100 mg/m2 IV Q3W, donafenib 200 mg PO BID, and tislelizumab 200 mg IV Q3W until disease progression, unacceptable toxicity, or withdrawal of consent whichever occurred first. The primary endpoint was safety and secondary endpoints included disease control rate (DCR), objective response rate (ORR), conversion rate, and overall survival (OS). RESULTS: A total of 13 patients were enrolled. The median follow-up time was 420 days (range 345-487). The median duration of treatment was four cycles (range 1-15). The incidence of ≥Grade 3 treatment-related adverse events (TRAEs) was 53.8% and no Grade 5 TRAE. The most frequent Grade 3-4 TRAEs were rash (4/13, 30.8%), platelet count decreased (2/13, 15.4%), and fatigue (2/13, 15.4%). Tumor response was assessed in eight evaluable patients; ORR was 25.0% (95% CI, 3.2%-65.1%) and DCR 87.5% (95% CI, 47.3%-99.7%). The median PFS was 4.8 months (95% CI, 1.25-NE). Three Stage III patients underwent subsequent surgery with a conversion rate of 23.1%. The median OS was not estimable. CONCLUSIONS: GEMOX combined with donafenib plus tislelizumab as the first-line therapy for unresectable BTC showed manageable toxicity and encouraging efficacy especially in terms of promising conversion rate in Stage III patients.

Intercalant-induced V t2g orbital occupation in vanadium oxide cathode toward fast-charging aqueous zinc-ion batteries.

Intercalation-type layered oxides have been widely explored as cathode materials for aqueous zinc-ion batteries (ZIBs). Although high-rate capability has been achieved based on the pillar effect of various intercalants for widening interlayer space, an in-depth understanding of atomic orbital variations induced by intercalants is still unknown. Herein, we design an NH4+-intercalated vanadium oxide (NH4+-V2O5) for high-rate ZIBs, together with deeply investigating the role of the intercalant in terms of atomic orbital. Besides extended layer spacing, our X-ray spectroscopies reveal that the insertion of NH4+ could promote electron transition to 3dxy state of V t2g orbital in V2O5, which significantly accelerates the electron transfer and Zn-ion migration, further verified by DFT calculations. As results, the NH4+-V2O5 electrode delivers a high capacity of 430.0 mA h g-1 at 0.1 A g-1, especially excellent rate capability (101.0 mA h g-1 at 200 C), enabling fast charging within 18 s. Moreover, the reversible V t2g orbital and lattice space variation during cycling are found via ex-situ soft X-ray absorption spectrum and in-situ synchrotron radiation X-ray diffraction, respectively. This work provides an insight at orbital level in advanced cathode materials.

Monolayer Thiol Engineered Covalent Interface toward Stable Zinc Metal Anode.

Interface engineering of zinc metal anodes is a promising remedy to relieve their inferior stability caused by dendrite growth and side reactions. Nevertheless, the low affinity and additional weight of the protective coating remain obstacles to their further implementation. Here, aroused by DFT simulation, self-assembled monolayers (SAMs) are selectively constructed to enhance the stability of zinc metal anodes in dilute aqueous electrolytes. It is found that the monolayer thiol molecules relatively prefer to selectively graft onto the unstable zinc crystal facets through strong Zn-S chemical interactions to engineer a covalent interface, enabling the uniform deposition of Zn2+ onto (002) crystal facets. Therefore, dendrite-free anodes with suppressed side reactions can be achieved, proven by in situ optical visualization and differential electrochemical mass spectrometry (DEMS). In particular, the thiol endows the symmetric cells with a 4000 h ultrastable plating/stripping at a specific current density of 1.0 mA cm-2, much superior to those of bare zinc anodes. Additionally, the full battery of modified anodes enables stable cycling of 87.2% capacity retention after 3300 cycles. By selectively capping unstable crystal facets with inert molecules, this work provides a promising design strategy at the molecular level for stable metal anodes.

CRISPR-Guided Proximity Labeling of RNA-Protein Interactions.

Proximity labeling employs modified biotin ligases or peroxidases that produce reactive radicals to covalently label proximate proteins with biotin in living cells. The resulting biotinylated proteins can then be isolated and identified. A combination of programmable DNA targeting and proximity labeling that maps proteomic landscape at DNA elements with dCas9-APEX2 has been established in living cells. However, defining interactome at RNA elements has lagged behind. In combination with RNA-targeting CRISPR-Cas13, proximity labeling can also be used to identify proteins that interact with specific RNA elements in living cells. From this viewpoint, we briefly summarize the latest advances in CRISPR-guided proximity labeling in studying RNA-protein interactions, and we propose applying the most recent engineered proximity-labeling enzymes to study RNA-centric interactions in the future.

A novel prognostic index of stomach adenocarcinoma based on immunogenomic landscape analysis and immunotherapy options.

Stomach adenocarcinoma (STAD) is one of the most common malignant tumors worldwide. In this study, we attempted to construct a valid immune-associated gene prognostic index risk model that can predict the survival of patients with STAD and the efficacy of immune checkpoint inhibitors (ICIs) treatment. Transcriptome, clinical, and gene mutational data were obtained from the TCGA database. Immune-related genes were downloaded from the ImmPort and InnateDB databases. A total of 493 immune-related genes were identified to be enriched in functions associated with immune response, as well as in immune and tumor-related pathways. Further, 36 candidate genes related to the overall survival (OS) of STAD were obtained by weighted gene co-expression network analysis (WGCNA). Next, based on a Cox regression analysis, we constructed an immune-associated gene prognostic index (IAGPI) risk model based on eight genes, which was verified using the GEO STAD cohort. The patients were divided into two subsets according to their risk score. Patients in the low-risk group had better OS than those in the high-risk group. In the low-risk group, there were more CD8, activated memory CD4, and follicular helper T cells, and M1 macrophages, whereas monocytes, M2 macrophages, eosinophils, and neutrophils were more abundant in the high-risk group. The patients in the low-risk group were more sensitive to ICIs therapy. The IAGPI risk model can precisely predict the prognosis, reflect the tumor immune microenvironment, and predict the efficacy of ICIs therapy in patients with STAD.

Development and experimental verification of a prognosis model for cuproptosis-related subtypes in HCC.

BACKGROUND: Cuproptosis is a recently discovered mechanism of programmed cell death caused by intracellular aggregation of mitochondrial lipoylated proteins and destabilization of iron-sulfur proteins triggered by copper. Hepatocellular carcinoma (HCC) is a common malignant tumor with a poor prognosis. We aimed to predict the survival of patients with HCC using the cuproptosis-related gene (CRG) expression. METHODS: We analyzed the expression, methylation, and mutation status of CRGs in 538 HCC patients and correlated the date with clinical prognosis. HCC patients were divided into two clusters based on their CRG expression. The relationship between CRGs, risk genes, and the immune microenvironment was analyzed using the CIBERSORT algorithm and the single-cell data analysis method. A cuproptosis risk model was constructed according to the five risk genes using the LASSO COX method. To facilitate the clinical applicability of the proposed risk model, we constructed a nomogram and conducted an antineoplastic drug sensitivity analysis. RESULTS: Our results suggest that the expression levels of CRGs in HCC are regulated by methylation. The prognoses were significantly different between the patients of the two clusters. The prognostic risk score positively correlated with memory T cell activation and negatively correlated with natural killer (NK) and regulatory T cell activation. CONCLUSION: Our findings indicate the involvement of CRG regulation in HCC and provide new insights into prognosis assessment. Drug sensitivity analysis predicted drug candidates for the treatment of patients with different HCC subtypes.

The TTYH3/MK5 Positive Feedback Loop regulates Tumor Progression via GSK3-ß/ß-catenin signaling in HCC.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and identification of novel targets is necessary for its diagnosis and treatment. This study aimed to investigate the biological function and clinical significance of tweety homolog 3 (TTYH3) in HCC. TTYH3 overexpression promoted cell proliferation, migration, and invasion and inhibited HCCM3 and Hep3B cell apoptosis. TTYH3 promoted tumor formation and metastasis in vivo. TTYH3 upregulated calcium influx and intracellular chloride concentration, thereby promoting cellular migration and regulating epithelial-mesenchymal transition-related protein expression. The interaction between TTYH3 and MK5 was identified through co-immunoprecipitation assays and protein docking. TTYH3 promoted the expression of MK5, which then activated the GSK3ß/ß-catenin signaling pathway. MK5 knockdown attenuated the activation of GSK3ß/ß-catenin signaling by TTYH3. TTYH3 expression was regulated in a positive feedback manner. In clinical HCC samples, TTYH3 was upregulated in the HCC tissues compared to nontumor tissues. Furthermore, high TTYH3 expression was significantly correlated with poor patient survival. The CpG islands were hypomethylated in the promoter region of TTYH3 in HCC tissues. In conclusion, we identified TTYH3 regulates tumor development and progression via MK5/GSK3-ß/ß-catenin signaling in HCC and promotes itself expression in a positive feedback loop.

Silencing miRNA-324-3p protects against cerebral ischemic injury via regulation of the GATA2/A1R axis.

Previous studies have suggested that miR-324-3p is related to the pathophysiology of cerebral ischemia, but the mechanism underlying this relationship is unclear. In this study, we found that miR-324-3p expression was decreased in patients with acute ischemic stroke and in in vitro and in vivo models of ischemic stroke. miR-324-3p agomir potentiated ischemic brain damage in rats subjected to middle cerebral artery occlusion, as indicated by increased infarct volumes and cell apoptosis rates and greater neurological deficits. In a PC12 cell oxygen-glucose deprivation/reoxygenation model, a miR-324-3p mimic decreased cell viability and expression of the anti-apoptotic protein BCL2 and increased expression of the pro-apoptotic protein BAX and rates of cell apoptosis, whereas treatment with a miR-324-3p inhibitor had the opposite effects. Silencing miR-324-3p increased adenosine A1 receptor (A1R) expression through regulation of GATA binding protein 2 (GATA2). These findings suggest that silencing miR-324-3p reduces ischemic brain damage via the GATA2/A1R axis.

Identification of Four Novel COL4A5 Variants and Detection of Splicing Abnormalities in Three Chinese X-Linked Alport Syndrome Families.

Chronic renal disease associated with X-linked Alport syndrome (XLAS) is relatively rare. However, due to the lack of specificity in the pathologic and clinical manifestations of the disease, it is easy to be misdiagnosed. In this study, we included three Chinese families with XLAS and used targeted NGS to find gene variants. In family X1, the 36-year-old male proband had hematuria, massive proteinuria, sensorineural deafness and ESRD at 33. In silico prediction showed the novel c.1424-4C > G variant reduced the score of the normal 3' splice site from 0.47 to 0.00 (according to BDGP). Transcriptional analysis from his peripheral blood cells indicated that it caused the insertion of an amino acid [p.(Lys474_Gly475insVal)]. In family X2, the proband was a 32-year-old male, who had hematuria, proteinuria, hypertension, hearing loss and progressed into ESRD at 30 years. He carried a novel missense variant c.2777G > T p.(Gly926Val). In family X3, the proband, a 16-year-old male, had hematuria, massive proteinuria, sensorineural deafness and ESRD; the results of renal pathological findings were consistent with AS. He carried a novel variant c.4529-2A > T, so did his mother with ESRD and probable XLAS. Bioinformatic analysis with BDGP showed that it abolished the acceptor site from 0.83 to 0.00. RT-PCR analysis from his kidney tissue indicated that it caused exon 50 skipping and exon 50 skipping along with inserting a cryptic exon derived from intron 49 p.[Gly1510Aspfs*11, Gly1510Alafs*35]. Another novel missense variant c.1552G > A p.(Gly518Arg) was identified in his mother and his aunt. No skewed X-chromosome inactivation was involved in these two female patients. In conclusion, four novel variants in COL4A5 were identified and transcriptional analysis is essential to investigate the pathogenicity of intronic variants. Thus we found a rare event in a female patient with XLAS caused by two COL4A5 variants in trans.

Data-driven capacity estimation of commercial lithium-ion batteries from voltage relaxation.

Accurate capacity estimation is crucial for the reliable and safe operation of lithium-ion batteries. In particular, exploiting the relaxation voltage curve features could enable battery capacity estimation without additional cycling information. Here, we report the study of three datasets comprising 130 commercial lithium-ion cells cycled under various conditions to evaluate the capacity estimation approach. One dataset is collected for model building from batteries with LiNi0.86Co0.11Al0.03O2-based positive electrodes. The other two datasets, used for validation, are obtained from batteries with LiNi0.83Co0.11Mn0.07O2-based positive electrodes and batteries with the blend of Li(NiCoMn)O2 - Li(NiCoAl)O2 positive electrodes. Base models that use machine learning methods are employed to estimate the battery capacity using features derived from the relaxation voltage profiles. The best model achieves a root-mean-square error of 1.1% for the dataset used for the model building. A transfer learning model is then developed by adding a featured linear transformation to the base model. This extended model achieves a root-mean-square error of less than 1.7% on the datasets used for the model validation, indicating the successful applicability of the capacity estimation approach utilizing cell voltage relaxation.

ICA69 aggravates ferroptosis causing septic cardiac dysfunction via STING trafficking.

Previous studies have demonstrated that cardiomyocyte apoptosis, ferroptosis, and inflammation participate in the progress of sepsis-induced cardiomyopathy (SIC). Although Islet cell autoantigen 69 (ICA69) is an imperative molecule that could regulate inflammation and immune response in numerous illnesses, its function in cardiovascular disease, particularly in SIC, is still elusive. We confirmed that LPS significantly enhanced the expression of ICA69 in wild-type (WT) mice, macrophages, and cardiomyocytes. The knockout of ICA69 in lipopolysaccharide(LPS)-induced mice markedly elevated survival ratio and heart function, while inhibiting cardiac muscle and serum inflammatory cytokines, reactive oxygen (ROS), and ferroptosis biomarkers. Mechanistically, increased expression of ICA69 triggered the production of STING, which further resulted in the production of intracellular lipid peroxidation, eventually triggering ferroptosis and heart injury. Intriguingly, ICA69 deficiency only reversed the ferroptotic marker levels, such as prostaglandin endoperoxide synthase 2 (PTGS2), malonaldehyde (MDA), 4-hydroxynonenal (4HNE), glutathione peroxidase 4 (GPX4), superoxide dismutase (SOD), iron and lipid ROS, but had no effects on the xCT-dependent manner. Additionally, greater ICA69 level was identified in septic patients peripheralblood mononuclear cells (PBMCs) than in normal control groups. Generally, we unveil that ICA69 deficiency can relieve inflammation and ferroptosis in LPS-induced murine hearts and macrophages, making targeting ICA69 in heart a potentially promising treatment method for SIC.