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Increasing the molecular weight while maintaining mono-dispersity has been proved crucial in innovating high-performance photovoltaic materials in giant oligomeric acceptors. However, developing efficient giant oligomeric donors to replace the batch-varied polymers remains challenging due to a lack of design principles. Here, by designing two unique isomeric rhodanine-based linkers, we successfully regulate the assembly behaviors of giant dimeric donors (G-Dimer-Ds) and fabricate the first all-giant-oligomer OSCs pairing with giant dimeric acceptor DY. Multiple characterizations demonstrate the small homo-molecular interaction with strong thermal-driven assembly capability in G-Dimer-D2 simultaneously facilitates reducing energetic disorder, improving charge transport and obtaining stable morphology, resulting in a satisfactory efficiency of 15.70% and long-term photostability with an extrapolated T80 of ca.10,000 hours, and further enhancing thermal-driven assembly promotes efficiency of 16.05%. Our results provide construction approaches on efficient giant donors, and propose a promising type of OSC with completely definite structures, high efficiency and superior stability.

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BACKGROUND: Colonoscopic enteral tube placement using current methods has some shortcomings, such as the complexity of the procedure and tube dislodgement. The magnetic navigation technique (MNT) has been proven effective for nasoenteral feeding tube placement, and is associated with reduced cost and time to initiation of nutrition. This study attempted to develop a novel method for enteral tube placement using MNT. METHODS: The MNT device consisted of an external magnet and a 12 Fr tube with a magnet at the end. Ten swine were used, and bowel cleansing was routinely performed before colonoscopy. Intravenous anesthesia with propofol and ketamine was administered. A colonoscopic enteral tube was placed using the MNT. The position of the end of the enteral tube was determined by radiography, and angiography was performed to check for colonic perforations. Colonoscopy was used to detect intestinal mucosal damage after tube removal. RESULTS: MNT-assisted colonoscopic enteral tube placement was successfully completed in all pigs. The median operating time was 30 (26-47) min. No colon perforation was detected on colonography after enteral tube placement, and no colonic mucosal bleeding or injury was detected after the removal of the enteral tube. CONCLUSIONS: MNT-assisted colonoscopic enteral tube placement is feasible and safe in swine and may represent a valuable method for microbial therapy, colonic drainage, and host-microbiota interaction research in the future.

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OBJECTIVE: The objective of this study was to examine the utility of a combination of the modified Caprini score and D-dimer levels for the evaluation and management of lower extremity venous thrombosis following lung cancer surgery. The purpose was to offer insights for developing clinical intervention programs. METHODS: The study sample consisted of 224 patients who underwent surgery for lung cancer at the First Central Hospital of Baoding City. General patient data and D-dimer levels on the first day post-surgery were collected. The modified Caprini risk assessment score was calculated. All patients underwent ultrasonography of the lower limb veins before and after surgery to identify venous thrombosis in the lower limb veins. Differences in lower extremity venous thrombosis and D-dimer levels among patients in various modified Caprini score groups were compared and analyzed. RESULTS: Based on the modified Caprini risk assessment score, all patients were categorized into three groups: the low-risk, medium-risk, and high-risk groups. The groups did not differ significantly in terms of age, but the differences in the rates of lower extremity venous thrombosis in the low, intermediate, and high-risk Caprini risk groups (16.5%, 19.2%, and 37.1%, respectively) were statistically significant. Out of the total 224 patients, 47 (21%) were diagnosed with venous thromboembolisms post-surgery, and all of them had thrombosis of the intermuscular veins of the lower extremity. The difference in the modified Caprini risk assessment score between patients with and without lower extremity venous thrombosis was statistically significant (P = 0.035), as were the postoperative D-dimer levels (1.28 ± 1.64 vs. 2.69 ± 2.77, respectively; P < 0.05) between these two groups of patients. The modified Caprini risk assessment score showed an association with lower extremity venous thrombosis (r = 0.15, P = 0.56) with an area under the receiver operating characteristic curve (AUC) of 0.59. CONCLUSION: In this study, we found that combining the modified Caprini risk assessment score with D-dimer measurements enhanced the accuracy of assessing the severity of deep vein thrombosis (DVT). This combination can be beneficial in evaluating thrombosis risk post-lung cancer surgery and holds significant clinical utility.

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Here Fe2O(SeO3)2/Fe3C@NC catalysts with high performance were fabricated for zinc-air batteries (ZABs). The experimental results confirmed that the existence of Fe-O-Se bonds in Fe2O(SeO3)2 crystal phase, and the Fe-O-Se bonds could obviously enhance ORR and OER catalytic performance of Fe2O(SeO3)2/Fe3C@NC. Density functional theoretical calculations (DFT) confirmed that the Fe2O(SeO3)2 in Fe2O(SeO3)2/Fe3C@NC had a higher d-band center of Fe atom and a lower p-orbital coupling degree with its own lattice O atom than Fe2O3, which leads to Fe site of Fe2O(SeO3)2 being more likely to adsorb external oxygen intermediates. The Fe-O-Se bonds in Fe2O(SeO3)2 results in the modification of coordination environment of Fe atoms and optimizes the adsorption energy of Fe site for oxygen intermediates. Compared with Fe2O3/Fe3C@NC, the Fe2O(SeO3)2/Fe3C@NC showed obvious enhancements of ORR/OER catalytic activities with a half-wave potential of 0.91 V for ORR in 0.1 M KOH electrolyte and a low overpotential of 345 mV for OER at 10 mA cm-2 in a 1.0 M KOH electrolyte. The peak power density and specific capacity of Fe2O(SeO3)2/Fe3C@NC-based ZABs are higher than those of Pt/C+RuO2-ZABs. The above results demonstrate that the asymmetrical Fe-O-Se bonds in Fe2O(SeO3)2 plays a key role in improving the bifunctional catalytic activities of ORR/OER for ZABs.

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Background: Previous studies have highlighted the crucial role of Wnt7B in the development of various cancers, including breast, pancreatic, and gastric cancers. However, research into the involvement of Wnt7B is often confined to specific tumor types, with a noticeable lack of comprehensive studies spanning multiple cancer forms. The potential of Wnt7B as a diagnostic or prognostic cancer biomarker has not been fully explored. Methods: In this study, we combined bioinformatics and immunohistochemistry analyses to examine the expression patterns and functions of Wnt7B in cancerous and adjacent noncancerous tissues across a range of tumors. Results: Our data indicate that Wnt7B may serve as a novel prognostic biomarker and therapeutic target in certain cancers. Conclusion: We found significant upregulation of Wnt7B expression levels in the majority of cancer cases examined. Furthermore, Wnt7B can influence cancer prognosis by modulating the tumor microenvironment, immune cell infiltration, and tumor stemness, among other factors. Additionally, we examined the associations between anticancer drug sensitivity and Wnt7B expression, which could aid in the development of more precise clinical therapies.

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Influenza A virus (IAV) can cause infectious respiratory diseases in humans and animals. IAVs mutate rapidly through antigenic drift and shift, resulting in the emergence of numerous IAV subtypes and significant challenges for IAV detection. Therefore, achieving the simultaneous detection of multiple IAVs is crucial. In this work, three specific aptamers targeting the hemagglutination (HA) protein of the influenza A H5N1, H7N9, and H9N2 viruses were screened using a multichannel magnetic microfluidic chip. The aptamers exhibit nanomolar affinity and excellent specificity for the HA protein of H5N1, H7N9, and H9N2 viruses. Furthermore, three specific aptamers were truncated and labeled with different fluorescence markers to realize fluorescence quantitative detection of influenza A H5N1, H7N9, and H9N2 viruses through an aptamer sandwich assay in 1 h. The limit of detection (LOD) of the developed method is 0.38 TCID50/mL for the H5N1 virus, 0.75 TCID50/mL for the H7N9 virus, and 1.14 TCID50/mL for the H9N2 virus. The detection method has excellent specificity, strong anti-interference ability, and good reproducibility. This work provides a sensitive quantitative detection method for the H5N1, H7N9, and H9N2 viruses, enabling quantitative fluorescence detection for multiple IAV subtypes.

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The artificial photocatalytic synthesis based on graphitic carbon nitride (g-C3N4) for H2O2 production is evolving rapidly. However, the simultaneous production of high-value products at electron and hole sites remains a great challenge. Here, we use transformable potassium iodide to obtain semi-crystalline g-C3N4 integrated with the I-/I3- redox shuttle mediators for efficient generation of H2O2 and benzaldehyde. The system demonstrates a prominent catalytic efficiency, with a benzaldehyde yield of 0.78 mol g-1 h-1 and an H2O2 yield of 62.52 mmol g-1 h-1. Such a constructed system can achieve an impressive 96.25% catalytic selectivity for 2e- oxygen reduction, surpassing previously reported systems. The mechanism study reveals that the strong crystal electric field from iodized salt enhances photo-generated charge carrier separation. The I-/I3- redox mediators significantly boost charge migration and continuous electron and proton supply for dual-channel catalytic synthesis. This groundbreaking work in photocatalytic co-production opens neoteric avenues for high-value synthesis.

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Targeted precise point editing and knock-in can be achieved by homology-directed repair(HDR) based gene editing strategies in mammalian cells. However, the inefficiency of HDR strategies seriously restricts their application in precision medicine and molecular design breeding. In view of the problem that exogenous donor DNA cannot be efficiently recruited autonomously at double-stranded breaks(DSBs) when using HDR strategies for gene editing, the concept of donor adapting system(DAS) was proposed and the CRISPR/Cas9-Gal4BD DAS was developed previously. Due to the large size of SpCas9 protein, its fusion with the Gal4BD adaptor is inconvenient for protein expression, virus vector packaging and in vivo delivery. In this study, two novel CRISPR/Gal4BD-SlugCas9 and CRISPR/Gal4BD-AsCas12a DASs were further developed, using two miniaturized Cas proteins, namely SlugCas9-HF derived from Staphylococcus lugdunensis and AsCas12a derived from Acidaminococcus sp. Firstly, the SSA reporter assay was used to assess the targeting activity of different Cas-Gal4BD fusions, and the results showed that the fusion of Gal4BD with SlugCas9 and AsCas12a N-terminals had minimal distraction on their activities. Secondly, the HDR efficiency reporter assay was conducted for the functional verification of the two DASs and the corresponding donor patterns were optimized simultaneously. The results demonstrated that the fusion of the Gal4BD adaptor binding sequence at the 5'-end of intent dsDNA template (BS-dsDNA) was better for the CRISPR/Gal4BD-AsCas12a DAS, while for the CRISPR/Gal4BD-SlugCas9 DAS, the dsDNA-BS donor pattern was recommended. Finally, CRISPR/Gal4BD-SlugCas9 DAS was used to achieve gene editing efficiency of 24%, 37% and 31% respectively for EMX1, NUDT5 and AAVS1 gene loci in HEK293T cells, which was significantly increased compared with the controls. In conclusion, this study provides a reference for the subsequent optimization of the donor adapting systems, and expands the gene editing technical toolbox for the researches on animal molecular design breeding.

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AIM: Fascin is an actin-binding protein that promotes tumor metastasis. The inhibition of fascin on the progress of non-small cell lung cancer (NSCLC) is not very clear. Hence, this study explored the potential effect of NP-G2-044, a novel fascin inhibitor, in human NSCLC lines and the Lewis lung cancer (LCC) mice model. METHODS: The growth of cells was analyzed via CCK-8 assays, and the flow cytometry was adopted for cell cycle and apoptosis analysis, as well as the migration and invasion of NSCLC cells with or without NP-G2-044. The therapy of NP-G2-044, which synergizes with cisplatin and PD-1, was evaluated in the established xenograft Lewis's lung cancer of mice. RESULTS: Fascin was overexpressed in human NSCLC cells, and inhibition of fascin by NP-G2-044 attenuated NSCLC cell growth and remarkably undermined the ability of migration and invasion in vitro, which was related to the reduced epithelialmesenchymal transition (EMT) including downregulation of N-cadherin and vimentin, and upregulation of E-cadherin. Further results implied that the above changes may be partially mediated by the Wnt/ß-catenin pathway. In vivo, NP-G2-044 slowed down tumor development and enhanced overall survival alone, leading to synergistic anticancer effects with cisplatin or PD-1 inhibitor. CONCLUSION: Fascin inhibition could inhibit the metastasis of NSCLC and has the potential to enhance the efficacy of cisplatin and PD-1 inhibitors by blocking the Wnt/ß- catenin pathway.

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Single-atom catalysts with precise structure and extremely high catalytic efficiency remain a fervent focus in the fields of materials chemistry and catalytic science. Herein, a nickel-substituted polyoxometalate (POM) {NiSb6O4(H2O)3[ß-Ni(hmta)SbW8O31]3}15- (NiPOM) with one extremely exposed nickel site [NiO3(H2O)3] was synthesized using the conventional aqueous method. The uniform dispersion of single nickel center with well-defined structure was facilely achieved by anchoring nanosized NiPOM on graphene oxide (GO). The resulting NiPOM/GO can couple with CdS photoabsorber for the construction of low-cost and ultra-efficient hydrogen evolution system. The H2 yield can reach to 2753.27 mmol gPOM-1 h-1, which represents a record value among all the POM-based photocatalytic systems. Remarkablely, an extremely high hydrogen yield of 3647.28 mmol gPOM-1 h-1 was achieved with simultaneous photooxidation of commercial waste plastic, representing the first POM-based photocatalytic system for H2 evolution and waste plastic conversion. This work highlights a straightforward strategy for constructing extremely exposed single-metal site with precise microenvironment by facilely manipulating nanosized molecular cluster to control individual atom.

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NETosis happens when neutrophils are activated and neutrophil extracellular traps (NETs) are formed synchronously, which is a hallmark of psoriasis. However, the specific trigger that drives NET formation and the distinct contents and interaction with interleukin-36 receptor (IL-36R) of NETs remain to be further elucidated. This work identified NET formation driven by toll-like receptor (TLR) 3 ligand (especially polyinosinic-polycytidylic acid (Poly(I:C)) were enhanced by purinergic receptor P2X ligand-gated ion channel 7 receptor (P2X7R) ligands (especially adenosine 5'-triphosphate (ATP)). NET formation was accompanied by the secretion of inflammatory cytokines and characterized by IL-1ß decoration. NET formation blockade decreased expressions of inflammatory cytokines and chemokines, which consequently improved inflammatory responses. Additionally, imiquimod (IMQ)-induced psoriasiform symptoms including neutrophilic infiltration tended to be time-sensitive. Mouse primary keratinocytes and mice deficient in Il1rl2, which encodes IL-36R, mitigated inflammatory responses and NET formation, thereby delaying the pathophysiology of psoriasis. Together, the findings provided the therapeutic potential for IL-36 targeting NET inhibitors in psoriasis treatment.

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Herein, the reaction mechanism for the GaCl3-catalyzed Knoevenagel condensation of 2-formylindacenodithieno[3,2-b]thiophene (ITIC-CHO) and active methylene compound 1,1-dicyanomethylene-3-indanone (IC) to synthesize ITIC in the presence of acetic anhydride was investigated using the density functional theory (DFT) method. The calculated results indicate that this reaction follows a bimolecular GaCl3 catalytic mechanism. The free energy span for the monomolecular GaCl3 catalytic mechanism is the highest (31.8 kcal/mol), followed by the trimolecular GaCl3 catalytic mechanism (26.4 kcal/mol) and the bimolecular GaCl3 catalytic mechanism (26.3 kcal/mol). The trimolecular GaCl3 path and bimolecular GaCl3 path are competitive, but the former path is limited by the concentration of GaCl3. The inclusion of GaCl3 could stabilize the transition states of C-H activation. Compared to the GaCl3-catalyzed Knoevenagel condensation, that catalyzed by pyridine is not advantageous, owning a high energy span of 31.7 kcal/mol. These agree well with experimental results. This work could provide a novel theoretical understanding of the Knoevenagel condensation, which could inspire the development of a synthesis strategy for electron acceptor materials.

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High-performance organic cathode interlayers (CILs) play a crucial role in the advance of organic solar cells (OSCs). However, organic CILs have exhibited inferior performances to their inorganic counterparts over a long time, due to the inherent shortcoming of poor charge transporting capability. Here, we designed and synthesized a perylene-diimide (PDI) zwitterion PDI-B as high-performance organic CIL for OSCs. We revealed that an obvious H-aggregate of PDI-B was formed during the solution processing, thereby significantly enhancing the charge transporting capability of the CIL. Compared to the classic PDINN, the π-π stacking distance of PDI-B was reduced from 4.2 Å to 3.9 Å, which further facilitated the charge transport. Consequently, PDI-B showed a high conductivity of 1.81×10-3S/m; this is comparable to that of inorganic CILs. The binary OSC showed an elevated PCE of 19.23%, which is among the highest PCE values for binary OSCs. Benefitting from improved solvent resistance and good compatibility with large-area processing method of PDI-B, the photovoltaic performances of inverted and 1-cm2 OSC were significantly improved. The results from this work provide a new approach of optimizing the condensed structure of PDI film to boost the charge conductivity, opening an avenue to develop high-performance PDI-based CILs.

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A common problem for Zn alloys is the trade-off between antibacterial ability and biocompatibility. This paper proposes a strategy to solve this problem by increasing release ratio of Ca2+ ions, which is realized by significant refinement of CaZn13 particles through bottom circulating water-cooled casting (BCWC) and rolling. Compared with conventionally fabricated Zn-0.3Ca alloy, the BCWC-rolled alloy shows higher antibacterial abilities against E. coli and S. aureus, meanwhile much less toxicity to MC3T3-E1 cells. Additionally, plasticity, degradation uniformity, and ability to induce osteogenic differentiation in vitro of the alloy are improved. The elongation up to 49 %, which is the highest among Zn alloys with Ca, and is achieved since the sizes of CaZn13 particles and Zn grains are small and close. As a result, the long-standing problem of low formability of Zn alloys containing Ca has also been solved due to the elimination of large CaZn13 particles. The BCWC-rolled alloy is a promising candidate of making GBR membrane.

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Naturally derived compounds show promise as treatments for microbial infections. Polyphenols, abundantly found in various plants, fruits, and vegetables, are noted for their physiological benefits including antimicrobial effects. This study introduced a new set of acylated phloroglucinol derivatives, synthesized and tested for their antifungal activity in vitro against seven different pathogenic fungi. The standout compound, 3-methyl-1-(2,4,6-trihydroxyphenyl) butan-1-one (2b), exhibited remarkable fungicidal strength, with EC50 values of 1.39 µg/mL against Botrytis cinerea and 1.18 µg/mL against Monilinia fructicola, outperforming previously screened phenolic compounds. When tested in vivo, 2b demonstrated effective antifungal properties, with cure rates of 76.26% for brown rot and 83.35% for gray mold at a concentration of 200 µg/mL, rivaling the commercial fungicide Pyrimethanil in its efficacy against B. cinerea. Preliminary research suggests that 2b's antifungal mechanism may involve the disruption of spore germination, damage to the fungal cell membrane, and leakage of cellular contents. These results indicate that compound 2b has excellent fungicidal properties against B. cinerea and holds potential as a treatment for gray mold.

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The efficient synthesis of chiral macrocycles with highly enantioselective recognition remains a challenge. We have addressed this issue by synthesizing a pair of chiral macrocycles, namely, R/S-BINOL[2], achieving total isolated yields of up to 62% through a two-step reaction sequence. These macrocycles are readily purified by column chromatography over silica gel without the need for chiral separation, thus streamlining the overall synthesis. R/S-BINOL[2] demonstrated enantioselective recognition toward chiral ammonium salts, with enantioselectivity (KS/KR) values reaching up to 13.2, although less favorable separations were seen for other substrates. R/S-BINOL[2] also displays blue circularly polarized luminescence with a |glum| value of up to 2.2 × 10-3. The R/S-BINOL[2] macrocycles of this study are attractive as chiral hosts in that they both display enantioselective guest recognition and benefit from a concise, high-yielding synthesis. As such, they may have a role to play in chiral separations.

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BACKGROUND: Elderly patients with esophageal cancer can benefit from concurrent chemoradiotherapy (CCRT). However, the optimal concurrent chemotherapy regimen remains undetermined. We aimed to compare the efficacy and safety of CCRT with paclitaxel-based or S-1 regimens in treating elderly patients with esophageal squamous cell carcinoma (ESCC). METHODS: From January 2016 to November 2022, a total of 349 patients aged 70 and above with ESCC were included. The patient population was divided into two treatment groups: patients receiving paclitaxel-based CCRT were allocated to the TP group, and those receiving S-1 regimen CCRT were allocated to the S-1 group. Propensity score matching (PSM) was used to balance potential biases. Survival outcomes, overall response rate, and treatment-related toxicities were assessed. RESULTS: After PSM, there were 82 patients in each group. The median follow up of the surviving patients was 42.6 months (IQR 28.0-58.8 months). The 2-year overall survival (OS) rate (71.4% vs 65.4%; log-rank P = 0.010) and progression-free survival (PFS) rate (64.4% vs 58.0%; log-rank P = 0.048) were significantly higher in the TP group. Compared with the S-1 group, the TP group experienced a higher rate of grade 3 and above hematologic toxicities, such as leukopenia (47.6% vs 15.9%, P < 0.001) and neutropenia (35.4% vs 6.1%, P < 0.001). One patient in the TP group and two patients in the S-1 group had grade 5 toxic effects. CONCLUSIONS: Our findings suggest that paclitaxel-based CCRT was well tolerated in elderly patients with ESCC and provided significant survival benefits over S-1 regimen.

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This research adopted the Fischer indole synthesis method to continue constructing a novel drug-like chemical entity based on the guidance of isocryptolepine and obtained four series of derivatives: Y, Da, Db, and Dc. The antimicrobial activity of these derivatives against plant pathogens was further evaluated. The results showed that Dc-2 had the best antifungal effect against Botrytis cinerea, and its EC50 value was up to 1.29 µg/mL. In addition, an in vivo activity test showed that the protective effect of Dc-2 on apples was 82.2% at 200 µg/mL, which was better than that of Pyrimethanil (45.4%). Meanwhile, it was found by scanning electron microscopy and transmission electron microscopy that the compound Dc-2 affected the morphology of mycelia. The compound Dc-2 was found to damage the cell membrane by PI and ROS staining. Through experiments such as leakage of cell contents, it was found that the compound Dc-2 changed the permeability of the cell membrane and caused the leakage of substances in the cell. According to the above studies, compound Dc-2 can be used as a candidate lead compound for further structural optimization and development.

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The pursuit of innovative therapeutic strategies in oncology remains imperative, given the persistent global impact of cancer as a leading cause of mortality. Immunotherapy is regarded as one of the most promising techniques for systemic cancer therapies among the several therapeutic options available. Nevertheless, limited immune response rates and immune resistance urge us on an augmentation for therapeutic efficacy rather than sticking to conventional approaches. Ferroptosis, a novel reprogrammed cell death, is tightly correlated with the tumor immune environment and interferes with cancer progression. Highly mutant or metastasis-prone tumor cells are more susceptible to iron-dependent nonapoptotic cell death. Consequently, ferroptosis-induction therapies hold the promise of overcoming resistance to conventional treatments. The most prevalent post-transcriptional modification, RNA m6A modification, regulates the metabolic processes of targeted RNAs and is involved in numerous physiological and pathological processes. Aberrant m6A modification influences cell susceptibility to ferroptosis, as well as the expression of immune checkpoints. Clarifying the regulation of m6A modification on ferroptosis and its significance in tumor cell response will provide a distinct method for finding potential targets to enhance the effectiveness of immunotherapy. In this review, we comprehensively summarized regulatory characteristics of RNA m6A modification on ferroptosis and discussed the role of RNA m6A-mediated ferroptosis on immunotherapy, aiming to enhance the effectiveness of ferroptosis-sensitive immunotherapy as a treatment for immune-resistant malignancies.

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