Novel catalytic behavior of defective nanozymes with catalase-mimicking characteristics for the degradation of tetracycline.

Although nanozymes have shown significant potential in wastewater treatment, enhancing their degradation performance remains challenging. Herein, a novel catalytic behavior was revealed for defective nanozymes with catalase-mimicking characteristics that efficiently degraded tetracycline (TC) in wastewater. Hydroxyl groups adsorbed on defect sites facilitated the in-situ formation of vacancies during catalysis, thereby replenishing active sites. Additionally, electron transfer considerably enhanced the catalytic reaction. Consequently, numerous reactive oxygen species (ROS) were generated through these processes and subsequent radical reactions. The defective nanozymes, with their unique catalytic behavior, proved effective for the catalytic degradation of TC. Experimental results demonstrate that •OH, •O2-, 1O2 and e- were the primary contributors to the degradation process. In real wastewater samples, the normalized degradation rate constant for defective nanozymes reached 26.0 min-1 g-1 L, exceeding those of other catalysts. This study reveals the new catalytic behavior of defective nanozymes and provides an effective advanced oxidation process for the degradation of organic pollutants.

Unveiling the atlas of associations between 1,400 plasma metabolites and 24 tumors: Mendelian randomization analyses.

Background: Association between plasma metabolites and pan-cancer remains controversial. Herein, we performed a two-sample Mendelian randomization (MR) analysis to verify whether there is a causal relationship between the two and to point the way for cancer metabolism research. Methods: In our research, we downloaded 1,400 plasma metabolites from a large genome-wide association study (GWAS). We also obtained GWAS summary statistics for 24 types of cancers from the publicly available GWAS database, totaling 5,003,410 European individuals. We mainly used the fixed/random-effects inverse variance-weighted (IVW) method for two-sample MR analysis. Results: In a combined sample of 291,202 cancer cases and 4,712,208 controls, a total of 55 plasma metabolites were identified as causally associated with nine types of cancer as a result of our MR analysis [P<0.05, false discovery rate (FDR) <0.2], including methionine sulfone, gamma-glutamylcitrulline, alliin, tetradecanedioate, hexadecanedioate, glutarate, ceramide, linolenoylcarnitine, hydroxypalmitoyl sphingomyelin, 1-palmitoyl-2-linoleoyl-glycerylphosphorylcholine (1-palmitoyl-2-linoleoyl-GPC), 3-acetylphenol sulfate, retinol (vitamin a) to linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) ratio, etc. Reverse MR analysis revealed a causal relationship between lung cancer and the only plasma metabolite, 1-palmitoyl-2-linoleoyl-GPC (P<0.05, FDR <0.2). Conclusions: Our study provides a comprehensive atlas of cancer-related plasma metabolites, offering possible targets for cancer detection, as well as a reference for future research on tumorigenesis mechanisms and therapeutic targets.

Sirt6 Mono-ADP-Ribosylates YY1 to Promote Dystrophin Expression for Neuromuscular Transmission.

The degeneration of the neuromuscular junction (NMJ) and the decline in motor function are common features of aging, but the underlying mechanisms have remained largely unclear. This study reveals that Sirt6 is reduced in aged mouse muscles. Ablation of Sirt6 in skeletal muscle causes a reduction of Dystrophin levels, resulting in premature NMJ degeneration, compromised neuromuscular transmission, and a deterioration in motor performance. Mechanistic studies show that Sirt6 negatively regulates the stability of the Dystrophin repressor YY1 (Yin Yang 1). Specifically, Sirt6 mono-ADP-ribosylates YY1, causing its disassociation from the Dystrophin promoter and allowing YY1 to bind to the SMURF2 E3 ligase, leading to its degradation. Importantly, supplementation with nicotinamide mononucleotide (NMN) enhances the mono-ADP-ribosylation of YY1 and effectively delays NMJ degeneration and the decline in motor function in elderly mice. These findings provide valuable insights into the intricate mechanisms underlying NMJ degeneration during aging. Targeting Sirt6 could be a potential therapeutic approach to mitigate the detrimental effects on NMJ degeneration and improve motor function in the elderly population.

A gold nanoparticle-enhanced dCas9-mediated fluorescence resonance energy transfer for nucleic acid detection.

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas proteins coupled with pre-amplification have shown great potential in molecular diagnoses. However, the current CRISPR-based methods require additional reporters and time-consuming process. Herein, a gold nanoparticle (AuNP)-enhanced CRISPR/dCas9-mediated fluorescence resonance energy transfer (FRET) termed Au-CFRET platform was proposed for rapid, sensitive, and specific detection of nucleic acid for the first time. In the Au-CFRET sensing platform, AuNP was functionalized with dCas9 and used as nanoprobe. Target DNA was amplified with FAM-labeled primers and then precisely bound with AuNP-dCas9. The formed complex rendered the distance between AuNP acceptor and FAM donor to be short enough for the occurrence of FRET, thus resulting in fluorescence quenching. Moreover, AuNPs were demonstrated to enhance binding efficiency of dCas9 to target DNA in Au-CFRET system. The key factors regarding the FRET efficiency were analyzed and characterized in detail, including the length of donor/acceptor and the size of AuNPs. Under the optimal conditions, Au-CFRET could determinate CaMV35S promoter of genetically modified rice as low as 21 copies µL-1. Moreover, Au-CFRET sensing system coupled with one-step extraction and recombinase polymerase amplification can identify the genuine plant seeds within 30 min from sampling to results at room/body temperature without expensive equipment or technical expertise, and requires no additional exogenous reporters. Therefore, the proposed sensing platform significantly simplified the system and shortened the assay time for nucleic acid diagnoses.

Engineered transcription factor-binding diversed functional nucleic acid-based synthetic biosensor.

Engineered transcription factors (eTFs) binding diversed functional nucleic acids (dFNAs), as innovative biorecognition systems, have gradually become indispensable core elements for building synthetic biosensors. They not only circumvent the limitations of the original TF-based biosensing technologies, but also inject new vitality into the field of synthetic biosensing. This review aims to provide the first comprehensive and systematic dissection of the eTF-dFNA synthetic biosensor concept. Firstly, the core principles and interaction mechanisms of eTF-dFNA biosensors are clarified. Next, we elaborate on the construction strategies of eTF-dFNA synthetic biosensors, detailing methods for the personalized customization of eTFs (irrational design, rational design, and semi-rational design) and dFNAs (SELEX, modifying and predicting), along with the exploration of strategies for the flexible selection of signal amplification and output modes. Furthermore, we discuss the exceptional performance and substantial advantages of eTF-dFNA synthetic biosensors, analyzing them from four perspectives: recognition domain, detection speed, sensitivity, and construction methodology. Building upon this analysis, we present their outstanding applications in point-of-care diagnostics, food-safety detection, environmental monitoring, and production control. Finally, we address the current limitations of eTF-dFNA synthetic biosensors candidly and envision the future direction of this technology, aiming to provide valuable insights for further research and applications in this burgeoning field.

A mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery.

Intravesical therapy (IT) is widely used to tackle various urological diseases. However, its clinical efficacy is decreased by the impermeability of various barriers presented on the bladder luminal surface, including the urinary mucus layer and the densely packed tissue barrier. In this study, we report a mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery. Upon intravesical instillation, its poloxamer 407 (PLX) hydrogel gelated and adhered to the urothelium to prolong its intravesical retention. The urea afterwards diffused into the hydrogel, thus generating a concentration gradient. Urease-powered membrane nanomotors (UMN) without asymmetric surface engineering could catalyze the urea and migrate down this concentration gradient to deeply and unidirectionally penetrate the urothelial barrier. Moreover, the intravesical hybrid system-delivered gemcitabine could effectively inhibit the bladder tumor growth without inducing any side effect. Therefore, our mucoadhesive-to-penetrating nanomotors-in-hydrogel system could serve as an alternative to IT to meet the clinical need for more efficacious therapeutics for urological diseases.

WormCNN-Assisted Establishment and Analysis of Glycation Stress Models in C. elegans: Insights into Disease and Healthy Aging.

Glycation Stress (GS), induced by advanced glycation end-products (AGEs), significantly impacts aging processes. This study introduces a new model of GS of Caenorhabditis elegans by feeding them Escherichia coli OP50 cultured in a glucose-enriched medium, which better simulates human dietary glycation compared to previous single protein-glucose cross-linking methods. Utilizing WormCNN, a deep learning model, we assessed the health status and calculated the Healthy Aging Index (HAI) of worms with or without GS. Our results demonstrated accelerated aging in the GS group, evidenced by increased autofluorescence and altered gene expression of key aging regulators, daf-2 and daf-16. Additionally, we observed elevated pharyngeal pumping rates in AGEs-fed worms, suggesting an addictive response similar to human dietary patterns. This study highlights the profound effects of GS on worm aging and underscores the critical role of computer vision in accurately assessing health status and aiding in the establishment of disease models. The findings provide insights into glycation-induced aging and offer a comprehensive approach to studying the effects of dietary glycation on aging processes.

Incidence and type of adverse events in patients with cirrhosis receiving terlipressin: A systematic review and meta-analysis.

BACKGROUND: Terlipressin has been widely used for various cirrhosis-related complications, but its safety profile remains controversial. Herein, this issue was systematically evaluated. METHODS: All studies reporting adverse events (AEs) of terlipressin in cirrhosis were screened. Incidences were pooled using a random-effects model. Subgroup analyses were performed according to the patient's characteristics and treatment regimens. Interaction among subgroups was evaluated. RESULTS: Seventy-eight studies with 7257 patients with cirrhosis were included. The pooled incidences of any AEs, treatment-related AEs, any serious AEs (SAEs), treatment-related SAEs, treatment withdrawal due to AEs, and treatment withdrawal due to treatment-related AEs were 31%, 22%, 5%, 5%, 4%, and 4% in patients with cirrhosis receiving terlipressin, respectively. Patients with hepatorenal syndrome had higher incidences of any SAEs (29% vs. 0% vs. 0%, pinteraction = 0.01) and treatment-related SAEs (8% vs. 1% vs. 7%, pinteraction = 0.02) than those with variceal bleeding or ascites. Patients who received terlipressin with human albumin had higher incidences of any SAEs (18% vs. 1%, pinteraction = 0.04) and treatment-related SAEs (7% vs. 0%, pinteraction = 0.09) than those without albumin. Patients with total bilirubin level >4.3 mg/dL had higher incidences of any AEs (69% vs. 24%, pinteraction = 0.02), any SAEs (64% vs. 0%, pinteraction < 0.01), and treatment-related SAEs (8% vs. 1%, pinteraction = 0.04) than those ≤4.3 mg/dL. CONCLUSIONS: AEs are common in patients with cirrhosis receiving terlipressin and influenced by clinical scenarios, combination with albumin, and bilirubin levels.

A Gene Cluster of Mitochondrial Complexes Contributes to the Cognitive Decline of COVID-19 Infection.

"Brain fog," a persistent cognitive impairment syndrome, stands out as a significant neurological aftermath of coronavirus disease 2019 (COVID-19). Yet, the underlying mechanisms by which COVID-19 induces cognitive deficits remain elusive. In our study, we observed an upregulation in the expression of genes linked to the inflammatory response and oxidative stress, whereas genes associated with cognitive function were downregulated in the brains of patients infected with COVID-19. Through single-nucleus RNA sequencing (snRNA-seq) analysis, we found that COVID-19 infection triggers the immune responses in microglia and astrocytes and exacerbates oxidative stress in oligodendrocytes, oligodendrocyte progenitors (OPCs), and neurons. Further investigations revealed that COVID-19 infection elevates LUC7L2 expression, which inhibits mitochondrial oxidative phosphorylation (OXPHOS) and suppresses the expression of mitochondrial complex genes such as MT-ND1, MT-ND2, MT-ND3, MT-ND4L, MT-CYB, MT-CO3, and MT-ATP6. A holistic approach to protect mitochondrial complex function, rather than targeting a single molecular, should be an effective therapeutic strategy to prevent and treat the long-term consequences of "long COVID."

Biotemplated Janus Magnetic Microrobots Based on Diatomite for Highly Efficient Detection of Salmonella.

Foodborne illnesses caused by Salmonella bacteria pose a significant threat to public health. It is still challenging to detect them effectively. Herein, biotemplated Janus disk-shaped magnetic microrobots (BJDMs) based on diatomite are developed for the highly efficient detection of Salmonella in milk. The BJDMs were loaded with aptamer, which can be magnetically actuated in the swarm to capture Salmonella in a linear range of 5.8 × 102 to 5.8 × 105 CFU/mL in 30 min, with a detection limit as low as 58 CFU/mL. In addition, the silica surface of BJDMs exhibited a large specific surface area to adsorb DNA from captured Salmonella, and the specificity was also confirmed via tests of a mixture of diverse foodborne bacteria. These diatomite-based microrobots hold the advantages of mass production and low cost and could also be extended toward the detection of other types of bacterial toxins via loading different probes. Therefore, this work offers a reliable strategy to construct robust platforms for rapid biological detection in practical applications of food safety.

Innovative In Situ Passivation Strategy for High-Efficiency Sb2(S,Se)3 Solar Cells.

An effective defect passivation strategy is crucial for enhancing the performance of antimony selenosulfide (Sb2(S,Se)3) solar cells, as it significantly influences charge transport and extraction efficiency. Herein, a convenient and novel in situ passivation (ISP) technique is successfully introduced to enhance the performance of Sb2(S,Se)3 solar cells, achieving a champion efficiency of 10.81%, which is among the highest recorded for Sb2(S,Se)3 solar cells to date. The first principles calculations and the experimental data reveal that incorporating sodium selenosulfate in the ISP strategy effectively functions as an in situ selenization, effectively passivating deep-level cation antisite SbSe defect within the Sb2(S,Se)3 films and significantly suppressing non-radiative recombination in the devices. Space-charge-limited current (SCLC), photoluminescence (PL), and transient absorption spectroscopy (TAS) measurements verify the high quality of the passivated films, showing fewer traps and defects. Moreover, the ISP strategy improved the overall quality of the Sb2(S,Se)3 films, and fine-tuned the energy levels, thereby facilitating enhanced carrier transport. This study thus provides a straightforward and effective method for passivating deep-level defects in Sb2(S,Se)3 solar cells.

Protective role of the CD73-A2AR axis in cirrhotic cardiomyopathy through negative feedback regulation of the NF-κB pathway.

Background: Myocardial inflammation and apoptosis induced by cirrhosis are among the primary mechanisms of cirrhotic cardiomyopathy. CD73, a common extracellular nucleotidase also known as 5'-nucleotidase, is associated with the progression of inflammation and immunity in multiple organs. However, the mechanism by which CD73 contributes to myocardial inflammation and apoptosis in cirrhosis remains unclear. Methods: In this study, a cirrhotic cardiomyopathy model in mice was established by bile duct ligation. Myocardial-specific overexpression of CD73 was achieved by tail vein injection of AAV9 (adeno-associated virus)-cTNT-NT5E-mCherry, and cardiac function in mice was assessed using echocardiography. Myocardial inflammation infiltration and apoptosis were evaluated through pathological observation and ELISA assays. The expression of CD73, A2AR, apoptotic markers, and proteins related to the NF-κB pathway in myocardial tissue were measured. Results: In the myocardial tissue of the cirrhotic cardiomyopathy mouse model, the expression of CD73 and A2AR increased. Overexpression of CD73 in the myocardium via AAV9 injection and stimulation of A2AR with CGS 21680 inhibited myocardial inflammation and cardiomyocyte apoptosis induced by cirrhosis. Additionally, overexpression of CD73 suppressed the activation of the NF-κB pathway by upregulating the expression of the adenosine receptor A2A. Conclusion: Our study reveals that the CD73/A2AR signaling axis mitigates myocardial inflammation and apoptosis induced by cirrhosis through negative feedback regulation of the NF-κB pathway.

Engineering the Substrate Specificity of UDP-Glycosyltransferases for Synthesizing Triterpenoid Glycosides with a Linear Trisaccharide as Aided by Ancestral Sequence Reconstruction.

Triterpenoids have wide applications in the pharmaceutical and agricultural industries. The glycosylation of triterpenoids catalyzed by UDP-glycosyltransferases (UGTs) is a crucial method for producing valuable derivatives with enhanced functions. However, only a few UDP-glucosyltransferases have been reported to synthesize the rare triterpenoids with linear-chain trisaccharide at C3-OH. This study revealed that the UGT91H subfamily primarily contributed to the 2"-O-glycosylation of triterpenoids with high regioselectivity, then the substrate scope was further expanded by ancestral sequence reconstruction (ASR). With ancestral enzyme UGT91H_A1 as a model, the sequence-structure-function relationship was explored. A RTAS loop (R212/T213/A214/S215) was identified to affect the substrate specificity of UGT91H_A1. Transferring this RTAS loop to the corresponding position of UGT91H enzymes successfully expanded their substrate spectra. The functional role of RTAS loop was further elucidated by molecular dynamics simulation and quantum mechanical computation. UGT91H_A1 was applied to the low-cost synthesis of terpenoid rhamnosides with a linear trisaccharide in combining with a self-sufficient UDP-rhamnose regeneration system. Finally, we developed a phylogeny-based platform to efficiently mining new UGT91Hs from plant genomic data. This study provided robust biocatalysts for synthesizing various triterpenoid glycosides with a linear trisaccharide and demonstrated ASR as an efficient tool in engineering the function of UDP-glycosyltransferases.

Strain-Induced Photocatalytic H2 Production over BiVO4 in Pure Water without Any Cocatalyst.

In this study, BiVO4 nanosheets (BiVO4-NS) were prepared by a facile hydrothermal method. It is found that sonication-induced strain can effectively promote the H2 production over BiVO4-NS in the presence of pure water without any cocatalysts. With the assistance of the sonication, the H2 production over BiVO4-NS is 1.344 mmol·g-1 after 3 h simulated sunlight irradiation, which is 24.8 times higher than that of BiVO4-NS without sonication (0.054 mmol·g-1). In addition, the products of water oxidation are determined to be hydroxyl radicals and hydrogen peroxide. Moreover, BiVO4-NS also shows obviously enhanced photoactivity than that of the commercially available BiVO4 nanoparticles (BiVO4-C). The improved photoactivity of BiVO4-NS is attributed to the effective charge separation and low charge transfer resistance. The underlying mechanism of sonication-promoted water splitting is investigated by a variety of controlled experiments. The results show that ultrasonic waves can produce obvious strain inside the sample, which results in lattice distortion of BiVO4. Therefore, the conduction band of BiVO4 is obviously negative shifted, which is beneficial for H2 production. In addition, the strain in BiVO4 also produces local polarization of the sample, which effectively promotes the charge transfer and separation process. It is hoped that our study could provide a new strategy for achieving efficient photocatalytic water splitting.

Synaptic Transistors Using Scalable Graphene Nanoribbons.

Graphene has demonstrated potential for use in neuromorphic electronics due to its superior electrical properties. However, these devices are all based on graphene sheets without patterning, restricting its applications. Here, we demonstrate a graphene nanoribbon synaptic transistor (GNST), with the graphene nanoribbon (GNR) channels fabricated using an electro-hydrodynamically printed nanowire array as lithographic masks for scalable fabrication. The GNST shows tunable synaptic plasticity by spike duration, frequency, and number. Moreover, the device is energy-efficient and ambipolar and shows a regulated response by nanoribbon width. The characteristics of GNSTs are applicable to pattern recognition, showing an accuracy of 84.5%. The device is applicable to Pavlov's classical conditioning. This study reports the first synaptic transistor based on GNRs, providing new insights into future neuromorphic electronics.

What Happens in the Gut during the Formation of Neonatal Jaundice-Underhand Manipulation of Gut Microbiota?

Jaundice is a symptom of high blood bilirubin levels affecting about 80% of neonates. In neonates fed with breast milk, jaundice is particularly prevalent and severe, which is likely multifactorial. With the development of genomics and metagenomics, a deeper understanding of the neonatal gut microbiota has been achieved. We find there are accumulating evidence to indicate the importance of the gut microbiota in the mechanism of jaundice. In this paper, we present new comprehensive insight into the relationship between the microbiota and jaundice. In the new perspective, the gut is a crucial crossroad of bilirubin excretion, and bacteria colonizing the gut could play different roles in the excretion of bilirubin, including Escherichia coli as the main traffic jam causers, some Clostridium and Bacteroides strains as the traffic police, and most probiotic Bifidobacterium and Lactobacillus strains as bystanders with no effect or only a secondary indirect effect on the metabolism of bilirubin. This insight could explain why breast milk jaundice causes a longer duration of blood bilirubin and why most probiotics have limited effects on neonatal jaundice. With the encouragement of breastmilk feeding, our perspective could guide the development of new therapy methods to prevent this side effect of breastfeeding.

Local protein synthesis at neuromuscular synapses is required for motor functions.

Motor neurons are highly polarized, and their axons extend over great distances to form connections with myofibers via neuromuscular junctions (NMJs). Local translation at the NMJs in vivo has not been identified. Here, we utilized motor neuron-labeled RiboTag mice and the TRAP (translating ribosome affinity purification) technique to spatiotemporally profile the translatome at NMJs. We found that mRNAs associated with glucose catabolism, synaptic connection, and protein homeostasis are enriched at presynapses. Local translation at the synapse shifts from the assembly of cytoskeletal components during early developmental stages to energy production in adulthood. The mRNA of neuronal Agrin (Agrn), the key molecule for NMJ assembly, is present at motor axon terminals and locally translated. Disrupting the axonal location of Agrn mRNA causes impairment of synaptic transmission and motor functions in adult mice. Our findings indicate that spatiotemporal regulation of mRNA local translation at NMJs plays critical roles in synaptic transmission and motor functions in vivo.

Three-Dimensional Printing of Yttrium Oxide Transparent Ceramics via Direct Ink Writing.

The utilization of 3D printing technology for the fabrication of intricate transparent ceramics overcomes the limitations associated with conventional molding processes, thereby presenting a highly promising solution. In this study, we employed direct ink writing (DIW) to prepare yttrium oxide transparent ceramics using a ceramic slurry with excellent moldability, solid content of 45 vol%, and shear-thinning behavior. A successfully printed transparent yttrium oxide ring measuring 30 mm in diameter, 10 mm in inner diameter, and 0.9 mm in thickness was obtained from the aforementioned slurry. After de-binding and sintering procedures, the printed ceramic exhibited in-line transmittance of 71% at 850 nm. This work not only produced complex yttria transparent ceramics with intricate shapes, but also achieved in-line transmittance that was comparable to that of the CIP method (79%), which can meet certain optical applications.

Hydrogen-Rich Gas Enhanced Sprint-Interval Performance: Metabolomic Insights into Underlying Mechanisms.

(1) Background: The diversity of blood biomarkers used to assess the metabolic mechanisms of hydrogen limits a comprehensive understanding of its effects on improving exercise performance. This study evaluated the impact of hydrogen-rich gas (HRG) on metabolites following sprint-interval exercise using metabolomics approaches, aiming to elucidate its underlying mechanisms of action. (2) Methods: Ten healthy adult males participated in the Wingate Sprint-interval test (SIT) following 60 min of HRG or placebo (air) inhalation. Venous blood samples were collected for metabolomic analysis both before and after gas inhalation and subsequent to completing the SIT. (3) Results: Compared with the placebo, HRG inhalation significantly improved mean power, fatigue index, and time to peak for the fourth sprint and significantly reduced the attenuation values of peak power, mean power, and time to peak between the first and fourth. Metabolomic analysis highlighted the significant upregulation of acetylcarnitine, propionyl-L-carnitine, hypoxanthine, and xanthine upon HRG inhalation, with enrichment pathway analysis suggesting that HRG may foster fat mobilization by enhancing coenzyme A synthesis, promoting glycerophospholipid metabolism, and suppressing insulin levels. (4) Conclusions: Inhaling HRG before an SIT enhances end-stage anaerobic sprint capabilities and mitigates fatigue. Metabolomic analysis suggests that HRG may enhance ATP recovery during interval stages by accelerating fat oxidation, providing increased energy replenishment for late-stage sprints.

The methyltransferase METTL3 regulates endothelial cell proliferation and inflammation via m6A RNA methylation-mediated TRAF1 expression.

The imbalance of vascular endothelial cell homeostasis is the key mechanism for the progression of many vascular diseases. RNA modification, particularly N6-Methyladenosine (m6A), plays important function in numerous biological processes. Nevertheless, the regulatory function of m6A RNA methylation in endothelial dysfunction remains insufficiently characterized. In this study, we established that the m6A methyltransferase METTL3 is critical for regulating endothelial function. Functionally, depletion of METTL3 results in decreased endothelial cells proliferation, survival and inflammatory response. Conversely, overexpression of METTL3 elicited the opposite effects. Mechanistically, MeRIP-seq identified that METTL3 catalyzed m6A modification of TRAF1 mRNA and enhanced TRAF1 translation, thereby up-regulation of TRAF1 protein. Over-expression of TRAF1 successfully rescued the inhibition of proliferation and adhesion of endothelial cells due to METTL3 knockdown. Additionally, m6A methylation-mediated TRAF1 expression can be reversed by the demethylase ALKBH5. Knockdown of ALKBH5 upregulated the level of m6A and protein level of TRAF1, and also increased endothelial cells adhesion and inflammatory response. Collectively, our findings suggest that METTL3 regulates vascular endothelium homeostasis through TRAF1 m6A modification, suggesting that targeting the METTL3-m6A-TRAF1 axis may hold therapeutic potential for patients with vascular diseases.