RESUMO
Stem-like properties contribute to tumor growth, metastasis, and chemoresistance. High-grade serous ovarian cancer (HGSOC) exhibits a very aggressive phenotype characterized by extensive metastasis, rapid progression, and therapy resistance. Frizzled 6 (FZD6) is overexpressed in HGSOC, and higher levels of FZD6 have been associated with shorter survival times in patients with HGSOC. Functionally, FZD6 promotes HGSOC growth and peritoneal metastasis. It endues HGSOC cells with stem-like properties by modulating POU5F1, ALDH1, and EPCAM. It can also desensitize HGSOC cells to certain chemical drugs. As a putative ligand for FZD6, WNT7B is also implicated in cell proliferation, stem-like properties, invasion and migration, and chemoresistance. SMAD7 is a downstream component of FZD6 signaling that is thought to mediate FZD6-associated phenotypes, at least in part. Therefore, FZD6/WNT7B-SMAD7 can be considered a tumor-promoting signaling pathway in HGSOC that may be responsible for tumor growth, peritoneal metastasis, and chemoresistance.
RESUMO
BACKGROUND: Postpartum depression (PPD) has received widespread attention. Shenzhen has been running a large-scale program for PPD since 2013. The program requires mothers to self-assess when applying information technology to PPD screening beginning in 2021. The purpose of this study was to conduct a longitudinal analysis of the impact of mHealth apps on the health-seeking behaviors of PPD patients. METHODS: Longitudinal data from districts in the Shenzhen Maternal and Child Health Management Information System (MCHMIS) for ten years was used in this study. Referral success rate (RSR, successful referrals to designated hospitals as a percentage of needed referrals) was used to assess health-seeking behavior. Trend χ2 tests were used to assess the overall trend of change after the implementation of mHealth in ten districts in Shenzhen. Interrupted Time Series Analysis (ITSA) was employed to assess the role of the mHealth app in changing patient health-seeking behaviors. RESULTS: For the results of the trend χ2 tests, the ten districts of Shenzhen showed an upward trend. For the ITSA results, different results were shown between districts. Nanshan district, Longhua district, and Longgang district all demonstrated an upward trend in the first-year application of the mHealth app. Nanshan district and Longgang district both exhibited an upward trend in terms of sustained effects. CONCLUSIONS: There is a difference in the performance of the mHealth app across the ten districts. The results show that the three districts with better health resource allocation, Nanshan, Longgang, and Longhua districts, demonstrated more significant mHealth app improvements. The mHealth app's functions, management systems, and health resource allocation may be potential factors in the results. This suggests that when leveraging mHealth applications, the first step is to focus on macro-level area resource allocation measures. Secondly, there should be effective process design and strict regulatory measures. Finally, there should also be appropriate means of publicity.
Assuntos
Depressão Pós-Parto , Aplicativos Móveis , Encaminhamento e Consulta , Telemedicina , Humanos , Feminino , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/terapia , Estudos Longitudinais , China , Encaminhamento e Consulta/estatística & dados numéricos , Adulto , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Análise de Séries Temporais Interrompida , Programas de Rastreamento/métodos , Gravidez , Política de SaúdeRESUMO
Metal-free molecular antiferroelectric (AFE) holds a promise for energy storage on account of its unique physical attributes. However, it is challenging to explore high-curie temperature (Tc) molecular AFEs, due to the lack of design strategies regarding the rise of phase transition energy barriers. By renewing the halogen substitution strategy, we have obtained a series of high-Tc molecular AFEs of the halogen-substituted phenethylammonium bromides (x-PEAB, x=H/F/Cl/Br), resembling the binary stator-rotator system. Strikingly, the p-site halogen substitution of PEA+ cationic rotators raises their phase transition energy barrier and greatly enhances Tc up to ~473â K for Br-PEAB, on par with the record-high Tc values for molecular AFEs. As a typical case, the member 4-fluorophenethylammonium bromide (F-PEAB) shows notable AFE properties, including high Tc (~374â K) and large electric polarization (~3.2â µC/cm2). Further, F-PEAB also exhibits a high energy storage efficiency (η) of 83.6 % even around Tc, catching up with other AFE oxides. This renewing halogen substitution strategy in the molecular AFE system provides an effective way to design high-Tc AFEs for energy storage devices.
RESUMO
2D Dion-Jacobson (DJ) phase hybrid perovskites have shown great promise in the photoelectronic field owing to their outstanding optoelectronic performance and superior structural rigidity. However, DJ phase lead-free double perovskites are still a virgin land with direct X-ray detection. Herein, we have designed and synthesized a new DJ phase lead-free layered double perovskite of (HIS)2 AgSbBr8 (1, HIS2+ = histammonium). Centimeter-sized (18 × 10 × 5 mm3 ) single crystals of 1 are successfully grown via the temperature cooling technique, exhibiting remarkable semiconductive characteristics such as a high resistivity (2.2 × 1011 Ω cm), a low trap state density (3.56 × 1010 cm-3 ), and a large mobility-lifetime product (1.72 × 10-3 cm2 V-1 ). Strikingly, its single-crystal-based X-ray detector shows a high sensitivity of 223 µC Gy-1 air cm-2 under 33.3 V mm-1 , a low detection limit (84.2 nGyair s-1 ) and superior anti-fatigue. As far as we know, we firstly demonstrates the potential of 2D DJ phase lead-free hybrid double perovskite in X-ray detection, showing excellent photoelectric response and operational stability. This work will pave a promising pathway to the innovative application of hybrid perovskites for eco-friendly and efficient X-ray detection.
RESUMO
OBJECTIVES: Contezolid acefosamil is a novel O-acyl phosphoramidate prodrug of contezolid. In the current study, we aimed to systemically evaluate the efficacy of contezolid acefosamil against infections caused by multiple Gram-positive pathogens, and compare the efficacy of the prodrug by oral and intravenous administrations. METHODS: The in vivo pharmacodynamic efficacy of contezolid acefosamil was evaluated in mouse models of systemic (with five S. aureus, three S. pneumoniae and two S. pyogenes bacterial isolates) and thigh (with two S. aureus isolates) infections using linezolid as the reference agent. RESULTS: In both models, contezolid acefosamil administrated either orally or intravenously, demonstrated high antibacterial efficacy similar to linezolid, and the antibacterial efficacy of oral and intravenous contezolid acefosamil were comparable. CONCLUSIONS: The high aqueous solubility and great efficacy of contezolid acefosamil support its clinical development as an injectable and oral antibiotic suitable for serious Gram-positive infections.
Assuntos
Pró-Fármacos , Animais , Camundongos , Linezolida , Pró-Fármacos/farmacologia , Staphylococcus aureus , Antibacterianos/uso terapêutico , Administração Intravenosa , Testes de Sensibilidade Microbiana , Administração OralRESUMO
Single atoms are interesting candidates for studying quantum optics and quantum information processing. Recently, trapping and manipulation of single atoms using tight optical dipole traps has generated considerable interest. Here we report an experimental investigation of the dynamics of atoms in a modified optical dipole trap with a backward propagating dipole trap beam, where a change in the two-atom collision rate by six times has been achieved. The theoretical model presented gives a prediction of high probabilities of few-atom loading rates under proper experimental conditions. This work provides an alternative approach to the control of the few-atom dynamics in a dipole trap and the study of the collective quantum optical effects of a few atoms.
RESUMO
A new congener of chuangxinmycin (CM) was identified from Actinoplanes tsinanensis CPCC 200056. Its structure was determined as 3-methylchuangxinmycin (MCM) by 1D and 2D NMR. MCM could be generated in vivo from CM by heterologous expression of the vitamin B12-dependent radical SAM enzyme CxnA/A1 responsible for methylation of 3-demethylchuangxinmycin (DCM) in CM biosynthesis, indicating that CxnA/A1 could perform iterative methylation for MCM production. In vitro assays revealed significant activities of CM, DCM, and MCM against Mycobacterium tuberculosis H37Rv and clinically isolated isoniazid/rifampin-resistant M. tuberculosis, suggesting that CM and its derivatives may have potential for antituberculosis drug development.
Assuntos
Antituberculosos , Mycobacterium tuberculosis , Metilação , Testes de Sensibilidade Microbiana , Antituberculosos/farmacologia , Rifampina , IsoniazidaRESUMO
Subplenones A-J (1-10), 10 new xanthone dimers, have been isolated and characterized from the endophytic fungus Subplenodomus sp. CPCC 401465, which resides within the Chinese medicinal plant Gentiana straminea. The isolation process was guided by antibacterial assays and molecular-networking-based analyses. The chemical structures of these compounds were elucidated through the interpretation of nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HRESIMS) data. Furthermore, the relative configuration of the compounds was determined using NMR and single-crystal X-ray diffraction analyses, and the absolute configuration was established using electronic circular dichroism calculations. All of the isolated compounds exhibited significant inhibitory activity against Gram-positive bacteria. Notably, compounds 1, 5, and 7 displayed remarkable inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 700698, with a minimum inhibitory concentration (MIC) of 0.25 µg/mL, and against vancomycin-resistant Enterococcus faecium (VRE) ATCC 700221, with MIC values ranging from 0.5 to 1.0 µg/mL.
Assuntos
Ascomicetos , Staphylococcus aureus Resistente à Meticilina , Plantas Medicinais , Xantonas , Antibacterianos/química , Testes de Sensibilidade Microbiana , Xantonas/farmacologia , Xantonas/química , Estrutura MolecularRESUMO
BACKGROUND: The rapid increase in production and application of carbon nanotubes (CNTs) has led to wide public concerns in their potential risks to human health. Single-walled CNTs (SWCNTs), as an extensively applied type of CNTs, have shown strong capacity to induce pulmonary fibrosis in animal models, however, the intrinsic mechanisms remain uncertain. RESULTS: In vivo experiments, we showed that accelerated senescence of alveolar type II epithelial cells (AECIIs) was associated with pulmonary fibrosis in SWCNTs-exposed mice, as well as SWCNTs-induced fibrotic lungs exhibited impaired autophagic flux in AECIIs in a time dependent manner. In vitro, SWCNTs exposure resulted in profound dysfunctions of MLE-12 cells, characterized by impaired autophagic flux and accelerated cellular senescence. Furthermore, the conditioned medium from SWCNTs-exposed MLE-12 cells promoted fibroblast-myofibroblast transdifferentiation (FMT). Additionally, restoration of autophagy flux with rapamycin significantly alleviated SWCNTs-triggered senescence and subsequent FMT whereas inhibiting autophagy using 3-MA aggravated SWCNTs-triggered senescence in MLE-12 cells and FMT. CONCLUSION: SWCNTs trigger senescence of AECIIs by impairing autophagic flux mediated pulmonary fibrosis. The findings raise the possibility of senescence-related cytokines as potential biomarkers for the hazard of CNTs exposure and regulating autophagy as an appealing target to halt CNTs-induced development of pulmonary fibrosis.
Assuntos
Nanotubos de Carbono , Fibrose Pulmonar , Humanos , Animais , Camundongos , Nanotubos de Carbono/toxicidade , Fibrose Pulmonar/induzido quimicamente , Células Epiteliais Alveolares , Autofagia , FibroblastosRESUMO
Mangrove actinomycetia have been proven to be one of the promising sources for discovering novel bioactive natural products. Quinomycins K (1) and L (2), two rare quinomycin-type octadepsipeptides without intra-peptide disulfide or thioacetal bridges, were investigated from the Maowei Sea mangrove-derived Streptomyces sp. B475. Their chemical structures, including the absolute configurations of their amino acids, were elucidated by a combination of NMR and tandem MS analysis, electronic circular dichroism (ECD) calculation, advanced Marfey's method, and further unequivocally confirmed by the first total synthesis. The two compounds displayed no potent antibacterial activity against 37 bacterial pathogens and had no significant cytotoxic activity against H460 lung cancer cells.
Assuntos
Equinomicina , Streptomyces , Streptomyces/metabolismo , Equinomicina/metabolismo , Antibacterianos/química , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
Novel components of the mitochondrial fission machinery, mitochondrial dynamics proteins of 49 kDa (MiD49) and 51 kDa (MiD51), have been recently described, and their potential therapeutic targets for treating cardiovascular disease have been shown, including acute myocardial infarction (AMI), anthracycline cardiomyopathy and pulmonary arterial hypertension (PAH). Here, we examined the role of MiD49 and MiD51 in atherosclerosis. MiD49/51 expression was increased in the aortic valve endothelial cells (ECs) of high-fat diet-induced atherosclerosis in ApoE-/-mice and IL-8-induced human umbilical vein endothelial cells (HUVECs), which accelerated dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Silencing MiD49/51 reduced atherosclerotic plaque size, increased collagen content, and decreased the IL-8-induced adhesion and proliferation of HUVECs. MiD51 upregulation resulted from decreased microRNA (miR)-107 expression and increased hypoxia-inducible factor-1a (HIF-1a) expression. Treatment with miR-107 mimics decreased atherosclerotic plaque size by reducing HIF-1α and MiD51 production. Both MiD49 and MiD51 were involved in atherosclerotic plaque formation through Drp1-mediated mitochondrial fission, and the involvement of MiD51 in this process was the result of decreased miR-107 expression and increased HIF-1α expression. The miR-107-HIF-1α-MiD51 pathway might provide new therapeutic targets for atherosclerosis.
Assuntos
Aterosclerose , MicroRNAs , Infarto do Miocárdio , Placa Aterosclerótica , Humanos , Animais , Camundongos , Dinâmica Mitocondrial , Dieta Hiperlipídica/efeitos adversos , Interleucina-8 , Aterosclerose/genética , Apolipoproteínas E/genética , Dinaminas , Células Endoteliais da Veia Umbilical Humana , Proteínas Mitocondriais/genética , MicroRNAs/genéticaRESUMO
Telecom fraud detection is of great significance in online social networks. Yet the massive, redundant, incomplete, and uncertain network information makes it a challenging task to handle. Hence, this paper mainly uses the correlation of attributes by entropy function to optimize the data quality and then solves the problem of telecommunication fraud detection with incomplete information. First, to filter out redundancy and noise, we propose an attribute reduction algorithm based on max-correlation and max-independence rate (MCIR) to improve data quality. Then, we design a rough-gain anomaly detection algorithm (MCIR-RGAD) using the idea of maximal consistent blocks to deal with missing incomplete data. Finally, the experimental results on authentic telecommunication fraud data and UCI data show that the MCIR-RGAD algorithm provides an effective solution for reducing the computation time, improving the data quality, and processing incomplete data.
RESUMO
With the rapid evolution of mobile communication networks, the number of subscribers and their communication practices is increasing dramatically worldwide. However, fraudsters are also sniffing out the benefits. Detecting fraudsters from the massive volume of call detail records (CDR) in mobile communication networks has become an important yet challenging topic. Fortunately, Graph neural network (GNN) brings new possibilities for telecom fraud detection. However, the presence of the graph imbalance and GNN oversmoothing problems makes fraudster detection unsatisfactory. To address these problems, we propose a new fraud detector. First, we transform the user features with the help of a multilayer perceptron. Then, a reinforcement learning-based neighbor sampling strategy is designed to balance the number of neighbors of different classes of users. Next, we perform user feature aggregation using GNN. Finally, we innovatively treat the above augmented GNN as weak classifier and integrate multiple weak classifiers using the AdaBoost algorithm. A balanced focal loss function is also used to monitor the model training error. Extensive experiments are conducted on two open real-world telecom fraud datasets, and the results show that the proposed method is significantly effective for the graph imbalance problem and the oversmoothing problem in telecom fraud detection.
RESUMO
A series of new N, N'-diarylurea derivatives were designed and synthesized, some of which exhibited potent antibacterial activity against the drug-susceptible and drug-resistant Gram-positive strains. Especially, compounds 2c, 2g-2l showed broader antibacterial spectrum and more potent antibacterial activity (MIC = 0.30-2.72 µM) against MRSA and MRSE than the control levofloxacin (MIC = 0.69-22.14 µM). In addition, compounds 2c, 2g, 2h and 2l exhibited much better antibacterial activity (MIC = 1.29-2.86 µM) against VRE (E. faecium) than sorafenib (MIC = 275.37 µM), PK150 (MIC = 5.07-10.13 µM) and SC78 (MIC = 2.40-4.79 µM). More importantly, the low cytotoxicity of compounds on cell lines HeLa and HepG2 implied a relatively wide therapeutic window, which was of high importance for further study.
Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Sorafenibe , Relação Estrutura-AtividadeRESUMO
BACKGROUND: MicroRNA-1290 (miR-1290) has been reported to be involved in many diseases and play a key role during the development process. However, the role of miR-1290 in atherosclerosis (AS) is still unclear. METHODS AND RESULTS: The current study showed that the expressions of miR-1290 were high in serum of patients with hyperlipidemia. The functional role of miR-1290 were then investigated in human umbilical vein endothelial cells (HUVECs). Here, we found that miR-1290 expressions were notably enhanced in HUVECs mediated by IL-8. miR-1290 inhibitor repressed monocytic THP-1 cells adhesion to HUVECs by regulating ICAM-1 and VCAM-1, inhibited proliferation through regulating cyclinD1 and PCNA, and inhibited inflammatory response by regulating IL-1ß. Mechanistically, we verified that miR-1290 mimic was able to directly target the 3'-UTR of GSK-3ß mRNA using luciferase reporter assay. Knockdown of GSK-3ß (si-GSK-3ß) promoted HUVECs adhesion and the expression of IL-1ß, and partially restore the depression effect of miR-1290 inhibitor on HUVECs adhesion and inflammation. In contrast, si-GSK-3ß inhibited the proliferation of HUVECs and the expression of cyclinD1 and PCNA. CONCLUSIONS: In summary, our study revealed that miR-1290 promotes IL-8-mediated the adhesion of HUVECs by targeting GSK-3ß. However, GSK-3ß is not the target protein for miR-1290 to regulate the proliferation of HUVECs. Our findings may provide potential target in atherosclerosis treatment.
Assuntos
Interleucina-8 , MicroRNAs , Apoptose , Proliferação de Células/genética , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Interleucina-8/genética , Interleucina-8/farmacologia , MicroRNAs/metabolismoRESUMO
Arbitrarily Oriented Object Detection in aerial images is a highly challenging task in computer vision. The mainstream methods are based on the feature pyramid, while for remote-sensing targets, the misalignment of multi-scale features is always a thorny problem. In this article, we address the feature misalignment problem of oriented object detection from three dimensions: spatial, axial, and semantic. First, for the spatial misalignment problem, we design an intra-level alignment network based on leading features that can synchronize the location information of different pyramid features by sparse sampling. For multi-oriented aerial targets, we propose an axially aware convolution to solve the mismatch between the traditional sampling method and the orientation of instances. With the proposed collaborative optimization strategy based on shared weights, the above two modules can achieve coarse-to-fine feature alignment in spatial and axial dimensions. Last but not least, we propose a hierarchical-wise semantic alignment network to address the semantic gap between pyramid features that can cope with remote-sensing targets at varying scales by endowing the feature map with global semantic perception across pyramid levels. Extensive experiments on several challenging aerial benchmarks show state-of-the-art accuracy and appreciable inference speed. Specifically, we achieve a mean Average Precision (mAP) of 78.11% on DOTA, 90.10% on HRSC2016, and 90.29% on UCAS-AOD.
RESUMO
As a major public health problem, the prevalence of Acinetobacter baumannii (A. baumannii) infections in hospitals due to the pathogen's multiple-antibiotic resistance has attracted extensive attention. We previously reported a series of 1,3-diamino-7H-pyrrolo[3,2-f]quinazoline (PQZ) compounds, which were designed by targeting Escherichia coli dihydrofolate reductase (ecDHFR), and exhibited potent antibacterial activities. In the current study, based on our molecular-modeling study, it was proposed that PQZ compounds may function as potent A. baumannii DHFR (abDHFR)-inhibitors as well, which inspired us to consider their anti-A. baumannii abilities. We further found that three PQZ compounds, OYYF-171, -172, and -175, showed significant antibacterial activities against A. baumannii, including multidrug-resistant (MDR) strains, which are significantly stronger than the typical DHFR-inhibitor, trimethoprim (TMP), and superior to, or comparable to, the other tested antibacterial agents belonging to ß-lactam, aminoglycoside, and quinolone. The significant synergistic effect between the representative compound OYYF-171 and the dihydropteroate synthase (DHPS)-inhibitor sulfamethoxazole (SMZ) was observed in both the microdilution-checkerboard assay and time-killing assay, which indicated that using SMZ in combination with PQZ compounds could help to reduce the required dosage and forestall resistance. Our study shows that PQZ is a promising scaffold for the further development of folate-metabolism inhibitors against MDR A. baumannii.
Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Antagonistas do Ácido Fólico , Humanos , Quinazolinas/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antagonistas do Ácido Fólico/farmacologia , Tetra-Hidrofolato Desidrogenase , Farmacorresistência Bacteriana MúltiplaRESUMO
A group of peptide metabolites (1-4), designated as mintaimycins, were isolated from Micromonospora sp. C-3509. The planar structures of mintaimycins were determined by combination of mass spectrometry, 1D and 2D NMR spectroscopy, and the stereochemistry of mintaimycins were partially resolved by Marfey's or Mosher's method. Mintaimycins featured a central ß-methylphenylalanine or phenylalanine linked at its amino group with 5-methyl-2-hexenoic acid, and at its carboxyl group with 5-hydroxy-norleucine or leucine that combined a derivative of hexanoic acid or 4-methylpentanoic acid. Mintaimycin A1 (1), the principal component, was found to exhibit the biological activity of inducing pre-adipocyte differentiation of 3T3-L1 fibroblast cells at 10.0 µmol/L.
Assuntos
Micromonospora , Peptídeos , Espectrometria de Massas , Micromonospora/química , Micromonospora/metabolismo , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peptídeos/química , Peptídeos/metabolismoRESUMO
Microresonators on a photonic chip could enhance nonlinear optics effects and thus are promising for realizing scalable high-efficiency frequency conversion devices. However, fulfilling phase matching conditions among multiple wavelengths remains a significant challenge. Here, we present a feasible scheme for degenerate sum-frequency conversion that only requires the two-mode phase matching condition. When the drive and the signal are both near resonance to the same telecom mode, an on-chip photon-number conversion efficiency up to 42% is achieved, showing a broad tuning bandwidth over 250 GHz. Furthermore, cascaded Pockels and Kerr nonlinear optical effects are observed, enabling the parametric amplification of the optical signal to distinct wavelengths in a single device. The scheme demonstrated in this Letter provides an alternative approach to realizing high-efficiency frequency conversion and is promising for future studies on communications, atom clocks, sensing, and imaging.
RESUMO
Transmembrane protein 98 (TMEM98) is a novel gene, and its function has not been well investigated. In a prior study, we have shown that siRNA-mediated knockdown of TMEM98 inhibited interleukin-8 (IL-8) promoted endothelial cell (EC) adhesion, as well as vascular smooth muscle cell (VSMC) proliferation and migration in the vascular endothelial and smooth muscle cell dysfunction. Herein, we used gain- and loss-of-function approaches combined with biochemical techniques to further explore the role of TMEM98 in the vascular wall cell. The expression and secretion of TMEM98 was increased in cultured human umbilical vein endothelial cells (HUVECs) and VSMCs treated with IL-8 and platelet-derived growth factor-BB (PDGF-BB). Also, PDGF-BB secretion was increased in TMEM98-treated HUVECs and VSMCs. Thus, it appears that TMEM98 and PDGF-BB form a positive feedback loop in potentiation of EC adhesion, as well as VSMC proliferation and migration. Knockdown of TMEM98 mediated by siRNA inhibited PDGF-BB-promoted EC adhesion by downregulating the expression of ICAM-1 and VCAM-1, as well as impaired the proliferation and migration of VSMCs by suppressing the AKT/GSK3ß/cyclin D1 signaling pathway and reducing the expression of ß-catenin. Hence, TMEM98 promoted EC adhesion by inducing the expression of ICAM-1/VCAM-1 and triggered VSMC proliferation and migration by activating the ERK and AKT/GSK3ß signaling pathways. Taken together, TMEM98 may serve as a potential therapeutic target for the clinical treatment of vascular endothelial and smooth muscle cell dysfunction.