Blocking CTLA-4 promotes pressure overload-induced heart failure via activating Th17 cells.

Targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) with specific antibody offers long-term benefits for cancer immunotherapy but can cause severe adverse effects in the heart. This study aimed to investigate the role of anti-CTLA-4 antibody in pressure overload-induced cardiac remodeling and dysfunction. Transverse aortic constriction (TAC) was used to induce cardiac hypertrophy and heart failure in mice. Two weeks after the TAC treatment, mice received anti-CTLA-4 antibody injection twice a week at a dose of 10 mg/kg body weight. The administration of anti-CTLA-4 antibody exacerbated TAC-induced decline in cardiac function, intensifying myocardial hypertrophy and fibrosis. Further investigation revealed that anti-CTLA-4 antibody significantly elevated systemic inflammatory factors levels and facilitated the differentiation of T helper 17 (Th17) cells in the peripheral blood of TAC-treated mice. Importantly, anti-CTLA-4 mediated differentiation of Th17 cells and hypertrophic phenotype in TAC mice were dramatically alleviated by the inhibition of interleukin-17A (IL-17A) by an anti-IL-17A antibody. Furthermore, the C-X-C motif chemokine receptor 4 (CXCR4) antagonist AMD3100, also reversed anti-CTLA-4-mediated cardiotoxicity in TAC mice. Overall, these results suggest that the administration of anti-CTLA-4 antibody exacerbates pressure overload-induced heart failure by activating and promoting the differentiation of Th17 cells. Targeting the CXCR4/Th17/IL-17A axis could be a potential therapeutic strategy for mitigating immune checkpoint inhibitors-induced cardiotoxicity.

Effectiveness and safety of adjuvant treatment of tislelizumab with or without chemotherapy in patients with high-risk upper tract urothelial carcinoma: a retrospective, real-world study.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare subset of urothelial cancers with poor prognosis. No consensus exists on the benefit of adjuvant immunotherapy for patients with UTUCs after nephroureterectomy with curative intent and the existing studies are limited. Herein, this study aimed to evaluate the effectiveness and safety of adjuvant treatment of tislelizumab with or without chemotherapy in patients with high-risk UTUC. METHODS: A retrospective study was conducted on 63 patients with high-risk UTUC who received tislelizumab with or without gemcitabine-cisplatin (GC) chemotherapy regimen after surgery between January 2020 and December 2022. Data on demographic and clinical characteristics, surgical, outcomes, prognostic factors, and safety were collected and analyzed. RESULTS: Among the 63 patients with high-risk UTUC, the median age was 66 years (interquartile range 57-72), with 33 (52%) being male. The majority of patients with staged pT3 (44%) and pN0 (78%) disease. Fifty-one patients (81%) received tislelizumab plus GC chemotherapy, and 12 (19%) were treated with tislelizumab monotherapy. After the median follow-up of 26 months (range 1-47), 49 (78%) patients achieved stable disease. The 2-year disease-free survival (DFS) and 2-year overall survival were 78.68% (95% CI: 60.02-87.07%) and 81.40% (95% CI: 68.76-89.31%), respectively. The cycles of GC chemotherapy were independent prognostic factors for survival, with higher DFS (hazard ratio = 0.68, 95% CI, 0.50-0.93; p = 0.016) observed in the subgroup undergoing ≥ 3 cycles versus < 3 cycles of GC chemotherapy. Fifty-eight patients (92%) experienced at least one treatment-related adverse event (TRAE), with grade 3-4 TRAEs occurring in 13%. The most common grade 3-4 TRAEs were decreased white blood cells, thrombocytopenia, and ulcers. CONCLUSIONS: The study demonstrates promising clinical benefits and a manageable safety profile of the tislelizumab-based adjuvant regimen for patients with high-risk UTUC. This suggests that adjuvant immunotherapy represents a potential therapeutic strategy for this population.

Heavy-atom-free triplet benzothiophene-fused BODIPY derivatives for lipid droplet-specific biomaging and photodynamic therapy.

The twist fusion of a benzothiophene group and the introduction of a 4-methyloxystyryl donor group to the BODIPY core resulted in large spin-orbit coupling values and smaller singlet-triplet energy gaps for the novel infrared absorbed photosensitizers named BSBDP. They show a high reactive oxygen species efficiency exceeding 69% and a fluorescence quantum yield of 23% and are successfully applied in imaging-guided photodynamic therapy in vitro and in vivo.

The safety and prognostic evaluation of subsequent aortic surgery after thoracic endovascular aortic repair: a retrospective cohort study.

Background: Thoracic endovascular aortic repair (TEVAR) is a widely employed clinical procedure for treating various aortic pathologies. However, some patients require subsequent surgical interventions post-TEVAR, particularly due to life-threatening complications such as aortic dissection. This study aimed to evaluate the safety and prognosis associated with additional aortic surgeries following TEVAR. Methods: A retrospective analysis was conducted on 21 patients who underwent aortic surgery after TEVAR at Guangdong Provincial People's Hospital between September 2016 and August 2020. By compiling and reviewing perioperative data, we assessed surgical-related complications and survival rates. Results: Among the 21 patients, 95.2% were male, with an average age of 53 years. Preoperative comorbidities included hypertension in 15 individuals, abdominal aortic aneurysm in one patient, and coronary heart disease in two patients. The primary complications of TEVAR were stent leakage and retrograde aortic dissection, with the latter being the predominant type in subsequent aortic surgeries. The mean duration of aortic clamping during surgery was 130.0 minutes, with a deep hypothermic circulatory arrest time of 8.5 minutes. Postoperatively, two patients suffered in-hospital mortality, one developed renal dysfunction, four required re-entry into the operating room for further treatment, and the average length of hospital stay was 20 days. Following discharge, 14.3% of patients experienced complications, with central nervous system symptoms being the most prevalent. Kaplan-Meier survival analysis indicated a 5-year survival rate of 85.7%. Conclusions: Aortic surgical intervention following TEVAR is a safe therapeutic approach that can improve patient prognosis. However, meticulous management of the perioperative period is crucial for reducing the risk of complications and improving survival rates. This study provides valuable insights into aortic surgery post-TEVAR, but large-scale research is needed to validate these findings.

Anti-CTLA-4 m2a Antibody Exacerbates Cardiac Injury in Experimental Autoimmune Myocarditis Mice By Promoting Ccl5-Neutrophil Infiltration.

The risk for suffering immune checkpoint inhibitors (ICIs)-associated myocarditis increases in patients with pre-existing conditions and the mechanisms remain to be clarified. Spatial transcriptomics, single-cell RNA sequencing, and flow cytometry are used to decipher how anti-cytotoxic T lymphocyte antigen-4 m2a antibody (anti-CTLA-4 m2a antibody) aggravated cardiac injury in experimental autoimmune myocarditis (EAM) mice. It is found that anti-CTLA-4 m2a antibody increases cardiac fibroblast-derived C-X-C motif chemokine ligand 1 (Cxcl1), which promots neutrophil infiltration to the myocarditic zones (MZs) of EAM mice via enhanced Cxcl1-Cxcr2 chemotaxis. It is identified that the C-C motif chemokine ligand 5 (Ccl5)-neutrophil subpopulation is responsible for high activity of cytokine production, adaptive immune response, NF-κB signaling, and cellular response to interferon-gamma and that the Ccl5-neutrophil subpopulation and its-associated proinflammatory cytokines/chemokines promoted macrophage (Mφ) polarization to M1 Mφ. These altered infiltrating landscape and phenotypic switch of immune cells, and proinflammatory factors synergistically aggravated anti-CTLA-4 m2a antibody-induced cardiac injury in EAM mice. Neutralizing neutrophils, Cxcl1, and applying Cxcr2 antagonist dramatically alleviates anti-CTLA-4 m2a antibody-induced leukocyte infiltration, cardiac fibrosis, and dysfunction. It is suggested that Ccl5-neutrophil subpopulation plays a critical role in aggravating anti-CTLA-4 m2a antibody-induced cardiac injury in EAM mice. This data may provide a strategic rational for preventing/curing ICIs-associated myocarditis.

Cobalt/Iron Bimetallic Biochar Composites for Lead(II) Adsorption: Mechanism and Remediation Performance.

The performance of nano-zero-valent iron for heavy metal remediation can be enhanced via incorporation into bimetallic carbon composites. However, few economical and green approaches are available for preparing bimetallic composite materials. In this study, novel Co/Fe bimetallic biochar composites (BC@Co/Fe-X, where X = 5 or 10 represents the CoCl2 concentration of 0.05 or 0.1 mol L-1) were prepared for the adsorption of Pb2+. The effect of the concentration of cross-linked metal ions on Pb2+ adsorption was investigated, with the composite prepared using 0.05 mol L-1 Co2+ (BC@Co/Fe-5) exhibiting the highest adsorption performance. Various factors, including the adsorption period, Pb2+ concentration, and pH, affected the adsorption of Pb2+ by BC@Co/Fe-5. Further characterisation of BC@Co/Fe-5 before and after Pb2+ adsorption using methods such as X-ray diffraction and X-ray photoelectron spectroscopy suggested that the Pb2+ adsorption mechanism involved (i) Pb2+ reduction to Pb0 by Co/Fe, (ii) Co/Fe corrosion to generate Fe2+ and fix Pb2+ in the form of PbO, and (iii) Pb2+ adsorption by Co/Fe biochar. Notably, BC@Co/Fe-5 exhibited excellent remediation performance in simulated Pb2+-contaminated water and soil with good recyclability.

NIR-absorbing and emitting α,α-nitrogen-bridged BODIPY dimers with strong excitonic coupling.

Three new distinct NIR α,α-NH-bridged BODIPY dimers were prepared by a direct nucleophilic substitution reaction. The synergistic effects of the nitrogen bridges and strong excitonic coupling between each BODIPY unit play major roles in enhancing the delocalization of an electron spin over the entire BODIPY dimers. The in situ formed aminyl radical dimer showed an absorption maximum at 1040 nm.

Solid-State Emissive meso-Aryl/Alkyl-Substituted and Heteroatom-Mixed BOPPY Dyes: Syntheses, Structures, Physicochemical, Redox Properties, and Computational Analysis.

A series of solid-state emissive meso-aryl/alkyl-substituted and heteroatom-mixed bisBF2-anchoring fluorophore incorporating pyrrolyl-pyridylhydrazone (BOPPY) dyes have been developed by a one-pot condensation of ketonized or formylated pyrroles and 2-heterocyclohydrazine as well as the subsequent borylation coordination. Interestingly, the BOPPY dyes with meso-alkyl-substituted groups or oxygen-substituted pyridine moieties exhibit high fluorescence quantum yields (QYs) of up to 79%, the highest solid QY of 74%, and long lifetimes independent of polarity in the available BOPPYs. On the other hand, the BOPPYs with meso-aryl or N-substituted moieties display a high solution QY of up to 93% and slight emission wavelength maxima. However, the S-substituted BOPPY dye exhibited weak fluorescence in all studied solvents, which was attributed to the structural flexibility of the N-C-S bond and different from those BOPPYs with O or N substitution, indicated by quantum calculations. And the significant excited-state structural rearrangement in a polar solvent is further confirmed by femtosecond time-resolved transient absorption spectroscopy. More importantly, those novel and barely fluorescent BOPPYs in acetonitrile show advantageous aggregation-induced enhanced emission and viscosity-dependent activities. These advancements in the photophysical and electrochemical properties of BOPPY dyes offer valuable insights into their further development and potential applications.

Unsymmetrical Benzothieno-Fused BODIPYs as Efficient NIR Heavy-Atom-Free Photosensitizers.

Heavy-atom-free photosensitizers are potentially suitable for use in photodynamic therapy (PDT). In this contribution, a new family of unsymmetrical benzothieno-fused BODIPYs with reactive oxygen efficiency up to 50% in air-saturated toluene was reported. Their efficient intersystem crossing (ISC) resulted in the generation of both 1O2 and O2-• under irradiation. More importantly, the PDT efficacy of a respective 4-methoxystyryl-modified benzothieno-fused BODIPY in living cells exhibited an extremely high phototoxicity with an ultralow IC50 value of 2.78 nM. The results revealed that the incorporation of an electron-donating group at the α-position of the unsymmetrical benzothieno-fused BODIPY platform might be an effective approach for developing long-wavelength absorbing heavy-atom-free photosensitizers for precision cancer therapy.

Synthesis and Properties of Bright Red-to-NIR BODIPY Dyes for Targeting Fluorescence Imaging and Near-Infrared Photothermal Conversion.

An efficient synthesis of 3-pyrrolylBODIPY dyes has been developed from a rational mixture of various aromatic aldehydes and pyrrole in a straightforward condensation reaction, followed by in situ successively oxidative nucleophilic substitution using a one-pot strategy. These resultant 3-pyrrolylBODIPYs without blocking substituents not only exhibit the finely tunable photophysical properties induced by the flexible meso-aryl substituents but also serve as a valuable synthetic framework for further selective functionalization. As a proof of such potential, one 3-pyrrolylBODIPY dye (581/603 nm) through the installation of the morpholine group is applicable for lysosome-targeting imaging. Furthermore, an ethene-bridged 3,3'-dipyrrolylBODIPY dimer was constructed, which displayed a near-infrared (NIR) emission extended to 1200 nm with a large fluorescence brightness (2840 M-1 cm-1). The corresponding dimer nanoparticles (NPs) afforded a high photothermal conversion efficiency (PCE) value of 72.5%, eventually resulting in favorable photocytotoxicity (IC50 = 9.4 µM) and efficient in vitro eradication of HeLa cells under 808 nm laser irradiation, highlighting their potential application for photothermal therapy in the NIR window.

Strategic Construction of meso-Aryl-Substituted N,N-Carbonyl-Bridged Dipyrrinones as Small, Bright, and Tunable Fluorophores.

A series of novel N,N-carbonyl-bridged dipyrrinone fluorophores have been directly constructed from α-halogenated dipyrrinones, which are conveniently obtained from the acid-catalyzed hydrolysis of readily available α,α'-dihalodipyrrins. This novel methodology affords efficient modulation of the functional groups at both the meso- and α-positions of this fluorophore. These resultant dyes show tunable absorption and emission wavelengths, good molar absorption coefficients, relatively large Stokes shifts, and excellent fluorescence quantum yields up to 0.99, and have been successfully applied in both one- and two-photon fluorescence microscopy imaging in living cells.

Prediction Model for Postoperative Pressure Injury in Patients with Acute Type A Aortic Dissection.

OBJECTIVE: To establish a risk assessment model to predict postoperative National Pressure Injury Advisory Panel stage 2 or higher pressure injury (PI) risk in patients undergoing acute type A aortic dissection surgery. METHODS: This retrospective assessment included consecutive patients undergoing acute type A aortic dissection surgery in the authors' hospital from September 2017 to June 2021. The authors used LASSO (logistic least absolute shrinkage and selection operator) regression analysis to identify the most relevant variables associated with PI by running cyclic coordinate descent with 10-times cross-validation. The variables selected by LASSO regression analysis were subjected to multivariate logistic analysis. A calibration plot, receiver operating characteristic curve, and decision curve analysis were used to validate the model. RESULTS: There were 469 patients in the study, including 94 (27.5%) with postoperative PI. Ten variables were selected from LASSO regression: body mass index, diabetes, Marfan syndrome, stroke, preoperative skin moisture, hemoglobin, albumin, serum creatinine, platelet, and d-dimer. Four risk factors emerged after multivariate logistic regression: Marfan syndrome, preoperative skin moisture, albumin, and serum creatinine. The area under the receiver operating characteristic curve of the model was 0.765. The calibration plot and the decision curve analysis both suggested that the model was suitable for predicting postoperative PI. CONCLUSIONS: This study built an efficient predictive model that could help identify high-risk patients.

Dynamically stable co-assembled supramolecular BOPPY systems with chiral amplification.

New and dynamical chiral co-assembled systems bearing BOPPY were successfully developed with amplified CPL signals. Remarkably, these stable chiral co-assemblies prepared at high concentrations retain uniform microrods and exceptional chiroptical performance (glum = 0.028, ΦF = 14%) after 48 h.

Tuning of Redox Potentials and LUMO Levels of BODIPYs via Site-Selective Direct Cyanation.

Through a strong oxidant Pb(OAc)4 promoted oxidative nucleophilic hydrogen substitution, site-selective direct and stepwise cyanation of BODIPYs using tetrabutylammonium cyanide was developed to give α-cyanated BODIPY derivatives. Characterization of optical and electrochemical properties of these dyes provides substantial enhancement of the electron affinity, with a reduction potential and LUMO level as low as -0.04 V and -4.43 eV, respectively. Radical anions of these electron-deficient 3,5-dicyanated BODIPYs were characterized by absorption and EPR spectroscopy.

The role of surgeon's intuition for acute type A aortic dissection in an era of evidence-based medicine: a prospective cohort study.

Background: Intuition may play a role in clinical practice. This prospective cohort study aimed to explore whether surgeons' intuition is valid in predicting the operative mortality of acute type A aortic dissection (ATAAD). Methods: After admission (before surgery), attending surgeons were asked to rate the mortality on a scale of 1 to 10, with 1 to 3 representing unlikely, 4-6 possible, and 7-10 very likely. The area under the curve (AUC) of receiver operating characteristic (ROC) analysis was performed to assess the accuracy of prediction models. Results: A significantly higher Surgeon's Score [5.0 (2.0, 8.0) vs. 8.0 (7.0, 10.0)] was observed in the mortality group, compared to the survival group. The odds ratio (OR) for Surgeon's Score was 1.32 [95% confidence interval (CI): 1.09-1.66, P=0.009]. Least absolute shrinkage and selection operator (LASSO) regression picked the following variables as significant predictors for early mortality of ATAAD: Surgeon's Score, Penn classification, age, aortic regurgitation, coronary artery disease, chronic obstructive pulmonary disease, platelet count, and ejection fraction. The AUC for the German Registry for Acute Aortic Dissection Type A (GERAADA) score and Surgeon's Score were 0.740 (95% CI: 0.625-0.854), and 0.710 (95% CI: 0.586-0.833), respectively. The combined model of GERAADA score and Surgeon's Score yielded an AUC of up to 0.761 (95% CI: 0.638-0.884). Conclusions: Intuition certainly has a place alongside evidence-based medicine. The duet of intuition and statistics-based scoring systems allows us to make more accurate predictions, potentially resulting in more rational clinical decisions.

Single-cell analysis of graft-infiltrating host cells identifies caspase-1 as a potential therapeutic target for heart transplant rejection.

Aims: Understanding the cellular mechanisms underlying early allograft rejection is crucial for the development of effective immunosuppressant strategies. This study aims to investigate the cellular composition of graft-infiltrating cells during the early rejection stage at a single-cell level and identify potential therapeutic targets. Methods: A heterotopic heart transplant model was established using enhanced green fluorescent protein (eGFP)-expressing mice as recipients of allogeneic or syngeneic grafts. At 3 days post-transplant, eGFP-positive cells infiltrating the grafts were sorted and subjected to single-cell RNA-seq analysis. Potential molecular targets were evaluated by assessing graft survival and functions following administration of various pharmacological inhibitors. Results: A total of 27,053 cells recovered from syngrafts and allografts were classified into 20 clusters based on expression profiles and annotated with a reference dataset. Innate immune cells, including monocytes, macrophages, neutrophils, and dendritic cells, constituted the major infiltrating cell types (>90%) in the grafts. Lymphocytes, fibroblasts, and endothelial cells represented a smaller population. Allografts exhibited significantly increased proportions of monocyte-derived cells involved in antigen processing and presentation, as well as activated lymphocytes, as compared to syngrafts. Differential expression analysis revealed upregulation of interferon activation-related genes in the innate immune cells infiltrating allografts. Pro-inflammatory polarization gene signatures were also enriched in these infiltrating cells of allografts. Gene profiling and intercellular communication analysis identified natural killer cells as the primary source of interferon-γ signaling, activating inflammatory monocytes that displayed strong signals of major histocompatibility complexes and co-stimulatory molecules. The inflammatory response was also associated with promoted T cell proliferation and activation in allografts during the early transplant stages. Notably, caspase-1 exhibited specific upregulation in inflammatory monocytes in response to interferon signaling. The regulon analysis also revealed a significant enrichment of interferon-related motifs within the transcriptional regulatory network of downstream inflammatory genes including caspase-1. Remarkably, pharmacological inhibition of caspase-1 was shown to reduce immune infiltration, prevent acute graft rejection, and improve cardiac contractile function. Conclusion: The single-cell transcriptional profile highlighted the crucial role of caspase-1 in interferon-mediated inflammatory monocytes infiltrating heart transplants, suggesting its potential as a therapeutic target for attenuating rejection.

Radiomics nomogram for prediction of glypican-3 positive hepatocellular carcinoma based on hepatobiliary phase imaging.

Introduction: The hepatobiliary-specific phase can help in early detection of changes in lesion tissue density, internal structure, and microcirculatory perfusion at the microscopic level and has important clinical value in hepatocellular carcinoma (HCC). Therefore, this study aimed to construct a preoperative nomogram for predicting the positive expression of glypican-3 (GPC3) based on gadoxetic acid-enhanced (Gd-EOB-DTPA) MRI hepatobiliary phase (HBP) radiomics, imaging and clinical feature. Methods: We retrospectively included 137 patients with HCC who underwent Gd-EOB-DTPA-enhanced MRI and subsequent liver resection or puncture biopsy at our hospital from January 2017 to December 2021 as training cohort. Subsequently collected from January 2022 to June 2023 as a validation cohort of 49 patients, Radiomic features were extracted from the entire tumor region during the HBP using 3D Slicer software and screened using a t-test and least absolute shrinkage selection operator algorithm (LASSO). Then, these features were used to construct a radiomics score (Radscore) for each patient, which was combined with clinical factors and imaging features of the HBP to construct a logistic regression model and subsequent nomogram model. The clinicoradiologic, radiomics and nomogram models performance was assessed by the area under the curve (AUC), calibration, and decision curve analysis (DCA). In the validation cohort,the nomogram performance was assessed by the area under the curve (AUC). Results: In the training cohort, a total of 1688 radiomics features were extracted from each patient. Next, radiomics with ICCs<0.75 were excluded, 1587 features were judged as stable using intra- and inter-class correlation coefficients (ICCs), 26 features were subsequently screened using the t-test, and 11 radiomics features were finally screened using LASSO. The nomogram combining Radscore, age, serum alpha-fetoprotein (AFP) >400ng/mL, and non-smooth tumor margin (AUC=0.888, sensitivity 77.7%, specificity 91.2%) was superior to the radiomics (AUC=0.822, sensitivity 81.6%, specificity 70.6%) and clinicoradiologic (AUC=0.746, sensitivity 76.7%, specificity 64.7%) models, with good consistency in calibration curves. DCA also showed that the nomogram had the highest net clinical benefit for predicting GPC3 expression.In the validation cohort, the ROC curve results showed predicted GPC3-positive expression nomogram model AUC, sensitivity, and specificity of 0.800, 58.5%, and 100.0%, respectively. Conclusion: HBP radiomics features are closely associated with GPC3-positive expression, and combined clinicoradiologic factors and radiomics features nomogram may provide an effective way to non-invasively and individually screen patients with GPC3-positive HCC.

Synthesis, Properties, and Semiconducting Characteristics of Bisbenzothieno[b]-Fused BODIPYs.

A novel family of bisbenzothieno[b]-fused BODIPYs containing seven fused aromatic rings has been developed from readily available benzothieo[3,2-b]pyrroles through an efficient two-step synthetic route, exhibiting planar skeletons with excellent photostabilities, deep-red absorptions, and near-infrared emissions (up to 753 nm). Importantly, the thin-film transistors based on BTB with a meso-dimethylamino-phenyl group exhibit unipolar n-type charge transporting characteristics with a high electron mobility of 0.013 cm2 V-1 s-1.

Human aortic smooth muscle cell regulation by METTL3 via upregulation of m6A NOTCH1 modification and inhibition of NOTCH1.

Background: Thoracic aortic dissection (TAD) is a very serious vascular condition that requires immediate treatment. Phenotypic conversion of human aortic smooth muscle cells (HASMCs) has been reported to be a causal factor for TAD development. Genetic variations affecting RNA modification may play a functional role in TAD. In this study, we aimed to explore the potential role of the methyltransferase like 3 (METTL3) and notch homolog 1 (NOTCH1) N6-methyladenosine (m6A) modification mechanisms in HASMCs. Methods: HASMCs were cultured. METTL3 was knocked down and overexpressed. Then, both METTL3 and NOTCH1 were simultaneously knocked down in HASMCs. HASMC proliferation was determined using Cell Counting Kit-8 (CCK-8). METTL3, NOTCH1, α-smooth muscle actin (α-SMA), smooth muscle protein 22-alpha (SM22α), and calponin expressions were monitored with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. An m6A dot blot assay was used to examine the m6A modification levels. The NOTCH1 3' untranslated region (3'UTR) m6A modification was analyzed using SRAMP and RMBase v. 2.0. A methylated RNA immunoprecipitation (MeRIP) assay was used to evaluate the METTL3 overexpression effect on m6A modification of NOTCH1 messenger RNA (mRNA). A dual-luciferase assay was used to investigate the effect of METTL3 binding of the NOTCH1 mRNA m6A modification site. YTH domain family 2 (YTHDF2)-RNA immunoprecipitation (RIP) was used to detect the change in YTHDF2's ability to bind to NOTCH1 mRNA after METTL3 overexpression. Results: Overexpression of METTL3 inhibited α-SMA, SM22α, calponin, and NOTCH1 expressions and promoted HASMC proliferation. Knocking down METTL3 had the opposite effect. The cointerference of the METTL3 and NOTCH1 results suggested that METTL3 regulated NOTCH1, contributing to HASMC phenotypic changes. The MeRIP assay showed that the m6A modification of NOTCH1 mRNA increased after METTL3 overexpression. The dual-luciferase assay indicated that the NOTCH1 mRNA m6A modification site and METTL3 overexpression promoted NOTCH1 mRNA degradation. YTHDF2-RIP further demonstrated that the binding ability of YTHDF2 and NOTCH1 mRNA was enhanced after METTL3 overexpression. Conclusions: METTL3 regulated the phenotypic changes of HASMC by upregulating m6A modification of NOTCH1 and inhibiting NOTCH1.