TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling.

TMEM16F, a Ca2+-activated lipid scramblase (CaPLSase) that dynamically disrupts lipid asymmetry, plays a crucial role in various physiological and pathological processes such as blood coagulation, neurodegeneration, cell-cell fusion, and viral infection. However, the mechanisms through which it regulates these processes remain largely elusive. Using endothelial cell-mediated angiogenesis as a model, here we report a previously unknown intracellular signaling function of TMEM16F. We demonstrate that TMEM16F deficiency impairs developmental retinal angiogenesis in mice and disrupts angiogenic processes in vitro. Biochemical analyses indicate that the absence of TMEM16F enhances the plasma membrane association of activated Src kinase. This in turn increases VE-cadherin phosphorylation and downregulation, accompanied by suppressed angiogenesis. Our findings not only highlight TMEM16F's intracellular signaling role in endothelial cells but also open new avenues for exploring the regulatory mechanisms of membrane lipid asymmetry and their implications in disease pathogenesis.

Deciphering and disrupting PIEZO1-TMEM16F interplay in hereditary xerocytosis.

ABSTRACT: Cell-surface exposure of phosphatidylserine (PS) is essential for phagocytic clearance and blood clotting. Although a calcium-activated phospholipid scramblase (CaPLSase) has long been proposed to mediate PS exposure in red blood cells (RBCs), its identity, activation mechanism, and role in RBC biology and disease remain elusive. Here, we demonstrate that TMEM16F, the long-sought-after RBC CaPLSase, is activated by calcium influx through the mechanosensitive channel PIEZO1 in RBCs. PIEZO1-TMEM16F functional coupling is enhanced in RBCs from individuals with hereditary xerocytosis (HX), an RBC disorder caused by PIEZO1 gain-of-function channelopathy. Enhanced PIEZO1-TMEM16F coupling leads to an increased propensity to expose PS, which may serve as a key risk factor for HX clinical manifestations including anemia, splenomegaly, and postsplenectomy thrombosis. Spider toxin GsMTx-4 and antigout medication benzbromarone inhibit PIEZO1, preventing force-induced echinocytosis, hemolysis, and PS exposure in HX RBCs. Our study thus reveals an activation mechanism of TMEM16F CaPLSase and its pathophysiological function in HX, providing insights into potential treatment.

A computational framework of routine test data for the cost-effective chronic disease prediction.

Chronic diseases, because of insidious onset and long latent period, have become the major global disease burden. However, the current chronic disease diagnosis methods based on genetic markers or imaging analysis are challenging to promote completely due to high costs and cannot reach universality and popularization. This study analyzed massive data from routine blood and biochemical test of 32 448 patients and developed a novel framework for cost-effective chronic disease prediction with high accuracy (AUC 87.32%). Based on the best-performing XGBoost algorithm, 20 classification models were further constructed for 17 types of chronic diseases, including 9 types of cancers, 5 types of cardiovascular diseases and 3 types of mental illness. The highest accuracy of the model was 90.13% for cardia cancer, and the lowest was 76.38% for rectal cancer. The model interpretation with the SHAP algorithm showed that CREA, R-CV, GLU and NEUT% might be important indices to identify the most chronic diseases. PDW and R-CV are also discovered to be crucial indices in classifying the three types of chronic diseases (cardiovascular disease, cancer and mental illness). In addition, R-CV has a higher specificity for cancer, ALP for cardiovascular disease and GLU for mental illness. The association between chronic diseases was further revealed. At last, we build a user-friendly explainable machine-learning-based clinical decision support system (DisPioneer: http://bioinfor.imu.edu.cn/dispioneer) to assist in predicting, classifying and treating chronic diseases. This cost-effective work with simple blood tests will benefit more people and motivate clinical implementation and further investigation of chronic diseases prevention and surveillance program.

EmAtlas: a comprehensive atlas for exploring spatiotemporal activation in mammalian embryogenesis.

The emerging importance of embryonic development research rapidly increases the volume for a professional resource related to multi-omics data. However, the lack of global embryogenesis repository and systematic analysis tools limits the preceding in stem cell research, human congenital diseases and assisted reproduction. Here, we developed the EmAtlas, which collects the most comprehensive multi-omics data and provides multi-scale tools to explore spatiotemporal activation during mammalian embryogenesis. EmAtlas contains data on multiple types of gene expression, chromatin accessibility, DNA methylation, nucleosome occupancy, histone modifications, and transcription factors, which displays the complete spatiotemporal landscape in mouse and human across several time points, involving gametogenesis, preimplantation, even fetus and neonate, and each tissue involves various cell types. To characterize signatures involved in the tissue, cell, genome, gene and protein levels during mammalian embryogenesis, analysis tools on these five scales were developed. Additionally, we proposed EmRanger to deliver extensive development-related biological background annotations. Users can utilize these tools to analyze, browse, visualize, and download data owing to the user-friendly interface. EmAtlas is freely accessible at http://bioinfor.imu.edu.cn/ematlas.

Mesenchymal stem cell-derived exosomes in myocardial infarction: Therapeutic potential and application.

Myocardial infarction refers to the irreversible impairment of cardiac function resulting from the permanent loss of numerous cardiomyocytes and the formation of scar tissue. This condition is caused by acute and persistent inadequate blood supply to the heart's arteries. In the treatment of myocardial infarction, Mesenchymal stem cells (MSCs) play a crucial role because of their powerful therapeutic effects. These effects primarily stem from the paracrine secretion of multiple factors by MSCs, with exosome-carried microRNAs being the most effective component in promoting cardiac function recovery after infarction. Exosome therapy has emerged as a promising cell-free treatment for myocardial infarction as a result of its relatively simple composition, low immunogenicity and controlled transplantation dose. Despite these advantages, maintaining the stability of exosomes after transplantation and enhancing their targeting effect remain significant challenges in clinical applications. In recent developments, several approaches have been designed to optimize exosome therapy. These include enhancing exosome retention, improving their ability to target specific effects, pretreating MSC-derived exosomes and employing transgenic MSC-derived exosomes. This review primarily focuses on describing the biological characteristics of exosomes, their therapeutic potential and their application in treating myocardial infarction.

Giant Deformation Induced Staggered-Layer Structure Promoting the Thermoelectric and Mechanical Performance in n-Type Bi2(Te, Se)3.

Bismuth telluride has long been recognized as the most promising near-room temperature thermoelectric material for commercial application; however, the thermoelectric performance for n-type Bi2(Te, Se)3-based alloys is far lagging behind that of its p-type counterpart. In this work, a giant hot deformation (GD) process is implemented in an optimized Bi2Te2.694Se0.3I0.006+3 wt%K2Bi8Se13 precursor and generates a unique staggered-layer structure. The staggered-layered structure, which is only observed in severely deformed crystals, exhibits a preferential scattering on heat-carrying phonons rather than charge-carrying electrons, thus resulting in an ultralow lattice thermal conductivity while retaining high-weight carrier mobility. Moreover, the staggered-layer structure is located adjacent to the van der Waals gap in Bi2(Te, Se)3 lattice and is able to strengthen the interaction between anion layers across the gap, leading to obviously improved compressive strength and Vickers hardness. Consequently, a high peak figure of merit ZT of ≈ 1.3 at 423 K, and an average ZT of ≈ 1.2 at 300-473 K can be achieved in GD sample. This study demonstrates that the GD process can successfully decouple the electrical and thermal transports with simultaneously enhanced mechanic performance.

iProbiotics: a machine learning platform for rapid identification of probiotic properties from whole-genome primary sequences.

Lactic acid bacteria consortia are commonly present in food, and some of these bacteria possess probiotic properties. However, discovery and experimental validation of probiotics require extensive time and effort. Therefore, it is of great interest to develop effective screening methods for identifying probiotics. Advances in sequencing technology have generated massive genomic data, enabling us to create a machine learning-based platform for such purpose in this work. This study first selected a comprehensive probiotics genome dataset from the probiotic database (PROBIO) and literature surveys. Then, k-mer (from 2 to 8) compositional analysis was performed, revealing diverse oligonucleotide composition in strain genomes and apparently more probiotic (P-) features in probiotic genomes than non-probiotic genomes. To reduce noise and improve computational efficiency, 87 376 k-mers were refined by an incremental feature selection (IFS) method, and the model achieved the maximum accuracy level at 184 core features, with a high prediction accuracy (97.77%) and area under the curve (98.00%). Functional genomic analysis using annotations from gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Rapid Annotation using Subsystem Technology (RAST) databases, as well as analysis of genes associated with host gastrointestinal survival/settlement, carbohydrate utilization, drug resistance and virulence factors, revealed that the distribution of P-features was biased toward genes/pathways related to probiotic function. Our results suggest that the role of probiotics is not determined by a single gene, but by a combination of k-mer genomic components, providing new insights into the identification and underlying mechanisms of probiotics. This work created a novel and free online bioinformatic tool, iProbiotics, which would facilitate rapid screening for probiotics.

Giant dielectric response and relaxation behavior of Bi3+/W6+ co-doped TiO2 ceramics.

With the rapid development of electronic information technology, dielectric ceramics are widely used in the field of passive devices such as multi-layer ceramic capacitors. In this paper, (Bi2/3W1/3)xTi1-xO2 (BWTOx) ceramics with superior dielectric properties have been prepared by using a traditional solid-state method. Remarkably, at a (Bi2/3W1/3)4+ doping level of 0.01, a (Bi2/3W1/3)0.01Ti0.99O2 ceramic achieved a giant dielectric permittivity of ∼1.5 × 104 and a low loss tangent of ∼0.07 at 1 kHz, as well as a good temperature independence, which could satisfy the operating temperature standards for X9R capacitors. The abnormal dielectric relaxation in the low temperature region can be explained by the interface polarization. Data based on the complex impedance spectroscopy and X-ray photoemission spectroscopy results indicate that the colossal permittivity of BWTOx ceramics is mainly ascribed to the internal barrier layer capacitance effect. The findings of this work could provide valuable insights for achieving large dielectric constants and good temperature stability simultaneously in BWTOx and other related electronic ceramic materials.

Superior Energy Storage Properties and Optical Transparency in K0.5 Na0.5 NbO3 -Based Dielectric Ceramics via Multiple Synergistic Strategies.

Eco-friendly transparent dielectric ceramics with superior energy storage properties are highly desirable in various transparent energy-storage electronic devices, ranging from advanced transparent pulse capacitors to electro-optical multifunctional devices. However, the collaborative improvement of energy storage properties and optical transparency in KNN-based ceramics still remains challenging. To address this issue, multiple synergistic strategies are proposed, such as refining the grain size, introducing polar nanoregions, and inducing a high-symmetry phase structure. Accordingly, outstanding energy storage density (Wtotal  ≈7.5 J cm-3 , Wrec  ≈5.3 J cm-3 ) and optical transmittance (≈76% at 1600 nm, ≈62% at 780 nm) are simultaneously realized in the 0.94(K0.5 Na0.5 )NbO3 -0.06Sr0.7 La0.2 ZrO3 ceramic, together with satisfactory charge-discharge performances (discharge energy density: ≈2.7 J cm-3 , power density: ≈243 MW cm-3 , discharge rate: ≈76 ns), surpassing previously reported KNN-based transparent ceramics. Piezoresponse force microscopy and transmission electron microscopy revealed that this excellent performance can be attributed to the nanoscale domain and submicron-scale grain size. The significant improvement in the optical transparency and energy storage properties of the materials resulted in the widening of the application prospects of the materials.

All Cubic-Phase δ-TAGS Thermoelectrics Over the Entire Mid-Temperature Range.

GeTe-based pseudo-binary (GeTe)x (AgSbTe2 )100- x (TAGS-x) is recognized as a promising p-type mid-temperature thermoelectric material with outstanding thermoelectric performance; nevertheless, its intrinsic structural transition and metastable microstructure (due to Ag/Sb/Ge localization) restrict the long-time application of TAGS-x in practical thermoelectric devices. In this work, a series of non-stoichiometric (GeTe)x (Ag1- δ Sb1+ δ Te2+ δ )100- x (x = 85∼50; δ = ≈0.20-0.23), referred to as δ-TAGS-x, with all cubic phase over the entire testing temperature range (300-773 K), is synthesized. Through optimization of crystal symmetry and microstructure, a state-of-the-art ZTmax of 1.86 at 673 K and average ZTavg of 1.43 at ≈323-773 K are realized in δ-TAGS-75 (δ = 0.21), which is the highest value among all reported cubic-phase GeTe-based thermoelectric systems so far. As compared with stoichiometric TAGS-x, the remarkable thermoelectric achieved in cubic δ-TAGS-x can be attributed to the alleviation of highly (electrical and thermal) resistive grain boundary Ag8 GeTe6 phase. Moreover, δ-TAGS-x exhibits much better mechanical properties than stoichiometric TAGS-x, together with the outstanding thermoelectric performance, leading to a robust single-leg thermoelectric module with ηmax of ≈10.2% and Pmax of ≈0.191 W. The finding in this work indicates the great application potential of non-stoichiometric δ-TAGS-x in the field of mid-temperature waste heat harvesting.

Dppa2/4 as a trigger of signaling pathways to promote zygote genome activation by binding to CG-rich region.

Developmental pluripotency-associated 2 (Dppa2) and developmental pluripotency-associated 4 (Dppa4) as positive drivers were helpful for transcriptional regulation of zygotic genome activation (ZGA). Here, we systematically assessed the cooperative interplay of Dppa2 and Dppa4 in regulating cell pluripotency and found that simultaneous overexpression of Dppa2/4 can make induced pluripotent stem cells closer to embryonic stem cells (ESCs). Compared with other pluripotency transcription factors, Dppa2/4 can regulate majorities of signaling pathways by binding on CG-rich region of proximal promoter (0-500 bp), of which 85% and 77% signaling pathways were significantly activated by Dppa2 and Dppa4, respectively. Notably, Dppa2/4 also can dramatically trigger the decisive signaling pathways for facilitating ZGA, including Hippo, MAPK and TGF-beta signaling pathways and so on. At last, we found alkaline phosphatase, placental-like 2 (Alppl2) was completely silenced when Dppa2 and 4 single- or double-knockout in ESC, which is consistent with Dux. Moreover, Alppl2 was significantly activated in mouse 2-cell embryos and 4-8 cells stage of human embryos, further predicted that Alppl2 was directly regulated by Dppa2/4 as a ZGA candidate driver to facilitate pre-embryonic development.

HelPredictor models single-cell transcriptome to predict human embryo lineage allocation.

The in-depth understanding of cellular fate decision of human preimplantation embryos has prompted investigations on how changes in lineage allocation, which is far from trivial and remains a time-consuming task by experimental methods. It is desirable to develop a novel effective bioinformatics strategy to consider transitions of coordinated embryo lineage allocation and stage-specific patterns. There are rapidly growing applications of machine learning models to interpret complex datasets for identifying candidate development-related factors and lineage-determining molecular events. Here we developed the first machine learning platform, HelPredictor, that integrates three feature selection methods, namely, principal components analysis, F-score algorithm and squared coefficient of variation, and four classical machine learning classifiers that different combinations of methods and classifiers have independent outputs by increment feature selection method. With application to single-cell sequencing data of human embryo, HelPredictor not only achieved 94.9% and 90.9% respectively with cross-validation and independent test, but also fast classified different embryonic lineages and their development trajectories using less HelPredictor-predicted factors. The above-mentioned candidate lineage-specific genes were discussed in detail and were clustered for exploring transitions of embryonic heterogeneity. Our tool can fast and efficiently reveal potential lineage-specific and stage-specific biomarkers and provide insights into how advanced computational tools contribute to development research. The source code is available at https://github.com/liameihao/HelPredictor.

N6-methyladenosine functions and its role in skin cancer.

N6-methyladenosine (m6A) methylation is the most abundant mammalian mRNA modification. m6A regulates RNA processing, splicing, nucleation, translation and stability by transferring, removing and recognizing m6A methylation sites, which are critical for cancer initiation, progression, metabolism and metastasis. m6A is involved in pathophysiological tumour development by altering m6A modification and expression levels in tumour oncogenes and suppressor genes. Skin cancers are by far the most common malignancies in humans, with well over a million cases diagnosed each year. Skin cancers are grouped into two main categories: melanoma and non-melanoma skin cancers (NMSC), based on cell origin and clinical behaviour. In this review, we summarize m6A methylation functions in different skin cancers, and discuss how m6A methylation is involved in disease development and progression. Moreover, we review potential prognostic biomarkers and molecular targets for early skin cancer diagnosis and treatment.

The origin of dielectric relaxation behavior in TiO2 based ceramics co-doped with Zn2+, W6+ ions under a N2/O2 sintering atmosphere.

Dense (Zn0.5W0.5)xTi1-xO2 (ZWTOx) ceramics were fabricated using a conventional solid state reaction method with sintering under a nitrogen atmosphere (ZWTOx-N2) and an oxygen atmosphere (ZWTOx-O2), respectively. Colossal permittivity (ε > 104) and low loss (tan δ < 0.1) were simultaneously achieved in ZWTOx-N2 ceramics, and two types of dielectric relaxation behaviors observed were interpreted to be due to interface polarization and disassociation between oxygen vacancies and trivalent titanium ions, respectively. The impedance plots suggested that the ZWTOx-N2 ceramics are electrical heterostructures composed of semiconductor and insulator grain boundaries, which proved that the CP performance of ZWTOx-N2 ceramics almost originates from the internal barrier layer capacitance (IBLC) effect. In addition, a series of anomalous dielectric behaviors such as low permittivity and low frequency dispersion were observed for ZWTOx-O2 ceramics; polarization (P)-electric field (E) hysteresis loop curves were obtained for ZWTOx-O2 ceramics, and that impedance plots have shown that the ZWTOx-O2 ceramics display higher insulation resistivity. Density functional theory (DFT) calculations illustrated that the Zn2+-W6+ ion pairs are easy to form in ZWTOx-O2 ceramics, which causes destruction of the local lattice and thus leads to abnormal dielectric behavior. This work will provide a new strategy for defect engineering in TiO2 and other CP materials.

TNN is first linked to auditory neuropathy.

Autosomal recessive nonsyndromic auditory neuropathy is attributed to a genetic etiology. We identified a compound heterozygous missense variant, c.G736A (p.G246S) and c.C2954T (p.T985 M) in TNN of affected patients in a pedigree via candidate gene screening and exome sequencing. To determine the genetic etiology of deafness in the pedigree with a heterozygous missense variant in the gene TNN encoding tenascin-W associated with autosomal recessive nonsyndromic auditory neuropathy, the cochlear expression of tenascin-W was evaluated at mRNA and protein levels in mice, and Tnn knock out mice were generated and utilized to study the function of Tnn in the auditory system. Immunofluorescence stainings showed that tenascin-W was mainly expressed in the somatic cytoplasm of spiral ganglion neurons of mice. Homozygous Tnn knockout was lethal in mice, whereas Tnn heterozygous mice showed decreases in spiral ganglion neuron density and progressive hearing loss. We demonstrate that tenascin-W is expressed in the murine cochleae and is essential for the development of spiral ganglion neurons. An abnormal expression of tenascin-W can influence the development and function of SGNs and affect the function of the auditory system.

eHSCPr discriminating the cell identity involved in endothelial to hematopoietic transition.

MOTIVATION: Hematopoietic stem cells (HSCs) give rise to all blood cells and play a vital role throughout the whole lifespan through their pluripotency and self-renewal properties. Accurately identifying the stages of early HSCs is extremely important, as it may open up new prospects for extracorporeal blood research. Existing experimental techniques for identifying the early stages of HSCs development are time-consuming and expensive. Machine learning has shown its excellence in massive single-cell data processing and it is desirable to develop related computational models as good complements to experimental techniques. RESULTS: In this study, we presented a novel predictor called eHSCPr specifically for predicting the early stages of HSCs development. To reveal the distinct genes at each developmental stage of HSCs, we compared F-score with three state-of-art differential gene selection methods (limma, DESeq2, edgeR) and evaluated their performance. F-score captured the more critical surface markers of endothelial cells and hematopoietic cells, and the area under receiver operating characteristic curve (ROC) value was 0.987. Based on SVM, the 10-fold cross-validation accuracy of eHSCpr in the independent dataset and the training dataset reached 94.84% and 94.19%, respectively. Importantly, we performed transcription analysis on the F-score gene set, which indeed further enriched the signal markers of HSCs development stages. eHSCPr can be a powerful tool for predicting early stages of HSCs development, facilitating hypothesis-driven experimental design and providing crucial clues for the in vitro blood regeneration studies. AVAILABILITY AND IMPLEMENTATION: http://bioinfor.imu.edu.cn/ehscpr. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

miR-24-3p obstructs the proliferation and migration of human skin fibroblasts after thermal injury by targeting PPAR-ß and positively regulated by NF-κB.

Thermal injury repair is a complex process during which the maintenance of the proliferation and migration of human skin fibroblasts (HSFs) exert a crucial role. MicroRNAs have been proven to exert an essential function in repairing skin burns. This study delves into the regulatory effects of miR-24-3p on the migration and proliferation of HSFs that have sustained a thermal injury, thereby, providing deeper insight into thermal injury repair pathogenesis. The PPAR-ß protein expression level progressively increased in a time-dependent manner on the 12th, 24th and 48th hour following the thermal injury of the HSFs. The knockdown of PPAR-ß markedly suppressed the proliferation of and migration of HSF. Following thermal injury, the knockdown also promoted the inflammatory cytokine IL-6, TNF-α, PTGS-2 and P65 expression. PPAR-ß contrastingly exhibited an opposite trend. A targeted relationship between PPAR-ß and miR-24-3p was predicted and verified. miR-24-3p inhibited thermal injured HSF proliferation and migration and facilitated inflammatory cytokine expression through the regulation of PPAR-ß. p65 directly targeted the transcriptional precursor of miR-24 and promoted miR-24 expression. A negative correlation between miR-24-3p expression level and PPAR-ß expression level in rats' burnt dermal tissues was observed. Our findings reveal that miR-24-3p is conducive to rehabilitating the denatured dermis, which may be beneficial in providing effective therapy of skin burns.

De novo Splice Site Mutation of the CHD7 Gene in a Chinese Patient with Typical CHARGE Syndrome.

INTRODUCTION: CHARGE syndrome (CS, OMIM 214800) is a rare genetic disease characterized by multiple congenital abnormalities, including coloboma, heart defect, atresia of the choanae, retardation of development, genital anomalies, and ear anomalies/deafness. The syndrome is mainly caused by a heterozygous variant in the chromodomain helicase DNA-binding protein 7 (CHD7) gene that encodes the CHD7 protein, involved in the ATP-dependent remodeling of chromatin. METHODS: In this study, the next-generation sequencing targeted panel was used to detect a de novo variant c.3523-2A>G in the CHD7 gene in a patient with severe CS, congenital heart disease, left coloboma of the choroid, cryptorchidism, and congenital deafness. The Sanger sequencing confirmed the variant and clarified it as de novo variant by short tandem repeat analysis in the patient family. We analyzed the effect of a variant by Minigene assay to evaluate the pathogenicity of the variant. RESULTS: In summary, cDNA analysis confirmed that c.3523-2A>G variant activates a cryptic splice site, resulting in 172 base pair missing in exon 15, leading to the premature truncation of the CHD7 protein (p.V1175Afs*11). CONCLUSION: The present study functionally characterized the novel c.3523-2A>G variant in CHD7, providing further confirmatory evidence that it is associated with CS.

m6A modification of mRNA in skin diseases. / çš®è‚¤ç— ä¸­ç¼–ç RNA的m6A修饰.

N6-methyladenosine (m6A) is the predominant post-transcriptional modification for eukaryotic mRNA. It's regulated by methyltransferases, demethylases, and m6A binding proteins, and plays an important role in regulating splicing, translation, and degradation of mRNA. Skin diseases, especially immune skin diseases and skin tumors, have a complicated pathogenesis and are refractory to treatment, seriously affecting the patient quality of life. Recent studies have revealed that m6A and its regulatory proteins can affect the development of numerous skin diseases. The m6A modification was found to be involved in skin accessory development, including hair follicle and sweat gland formation. The level of m6A modification was significantly altered in a variety of skin diseases including melanoma, cutaneous squamous cell carcinoma, Merkel cell carcinoma, and psoriasis, and affected a variety of biological processes including cell proliferation and differentiation migration. The m6A and its regulatory proteins may become potential molecular markers or therapeutic targets for skin diseases, and have promising clinical applications in early diagnosis, efficacy determination, prognosis prediction, and gene therapy of skin diseases.

Nucleolin regulates the proliferation of vascular smooth muscle cells in atherosclerotic via Aurora B.

Vascular smooth muscle cells (VSMCs) play a significant role in atherosclerosis. As a multifunctional protein, nucleolin (NCL) is involved in many important physiological and pathological processes. In this study, we aimed to investigate the role of nucleolin in VSMCs proliferation and cell cycle. The expression of nucleolin increased in VSMCs of mice with aortas advanced plaques. With the left common carotid-artery ligation-injury model, immunofluorescence staining revealed that nucleolin and Ki67 expression increased in VSMCs in mice left carotid artery compared with right carotid artery after surgery. POVPC or ox-LDL up-regulated nucleolin mRNA and protein expression in a dose- and time-dependent manner in HAVSMCs. POVPC (5µg/ml) or ox-LDL (50µg/ml) promoted the proliferation of HAVSMCs. Nucleolin ablation relieved the pro-proliferation role of VSMCs. The cell cycle assay and cell ability results showing that POVPC or ox-LDL increased the proliferation, but nucleolin ablation inhibited the proliferation of HAVSMCs. And nucleolin ablation can prevent DNA replication at S phase and induce cell cycle arrest in S phase. The bioinformatics database predicts protein-protein interactions with nucleolin and aurora B. Nucleolin overexpression and ablation affected the expression of aurora B. These findings indicate for the first time that nucleolin actively involved the proliferation of VSMCs via aurora B.