ABSTRACT
Transition-metal-based oxygen evolution reaction (OER) catalysts have attracted widespread attention due to their inexpensive prices, unique layered structures, and rich active sites. Currently, designing low-cost, sustainable, and simple synthesis methods is essential for the application of transition-metal-based catalysts. Here, magnetic field (MF)-assisted chemical corrosion, as a novel technology, is adopted to construct superior OER electrocatalysts. The produced Ni(Fe)(OH)2-Fe2O3 electrode exhibits an overpotential of 272 mV at a current density of 100 mA cm-2, presenting a 64 mV reduction compared to the electrode without an MF. The experimental results indicate that an MF can induce the directional growth of Fe2O3 rods and reduce their accumulation. In addition, an external MF is beneficial for the lattice dislocation of the obtained catalysts, which can increase the surface free energy, thus reducing the activation energy and accelerating the electrochemical reaction kinetics. This work effectively combines a magnetic field with chemical corrosion and electrochemical energy, which offers a novel strategy for the large-scale development of environmentally friendly and superior electrocatalysts.
ABSTRACT
MOTIVATION: Drug combination therapies have shown promise in clinical cancer treatments. However, it is hard to experimentally identify all drug combinations for synergistic interaction even with high-throughput screening due to the vast space of potential combinations. Although a number of computational methods for drug synergy prediction have proven successful in narrowing down this space, fusing drug pairs and cell line features effectively still lacks study, hindering current algorithms from understanding the complex interaction between drugs and cell lines. RESULTS: In this paper, we proposed a Permutable feature fusion network for Drug-Drug Synergy prediction, named PermuteDDS. PermuteDDS takes multiple representations of drugs and cell lines as input and employs a permutable fusion mechanism to combine drug and cell line features. In experiments, PermuteDDS exhibits state-of-the-art performance on two benchmark data sets. Additionally, the results on independent test set grouped by different tissues reveal that PermuteDDS has good generalization performance. We believed that PermuteDDS is an effective and valuable tool for identifying synergistic drug combinations. It is publicly available at https://github.com/littlewei-lazy/PermuteDDS . SCIENTIFIC CONTRIBUTION: First, this paper proposes a permutable feature fusion network for predicting drug synergy termed PermuteDDS, which extract diverse information from multiple drug representations and cell line representations. Second, the permutable fusion mechanism combine the drug and cell line features by integrating information of different channels, enabling the utilization of complex relationships between drugs and cell lines. Third, comparative and ablation experiments provide evidence of the efficacy of PermuteDDS in predicting drug-drug synergy.
ABSTRACT
Miltiradiene serves as a crucial precursor in the synthesis of various high-value abietane-type diterpenes, exhibiting diverse pharmacological activities. Previous efforts to enhance miltiradiene production have primarily focused on the mevalonate acetate (MVA) pathway. However, limited emphasis has been placed on optimizing the supply of acetyl-CoA and NADPH. In this study, we constructed a platform yeast strain for miltiradiene production by reinforcing the biosynthetic pathway of geranylgeranyl diphosphate (GGPP) and acetyl-CoA, and addressing the imbalance between the supply and demand of the redox cofactor NADPH within the cytoplasm, resulting in an increase in miltiradiene yield to 1.31 g/L. Furthermore, we conducted modifications to the miltiradiene synthase fusion protein tSmKSL1-CfTPS1. Finally, the comprehensive engineering strategies and protein modification strategies culminated in 1.43 g/L miltiradiene in the engineered yeast under shake flask culture conditions. Overall, our work established efficient yeast cell factories for miltiradiene production, providing a foothold for heterologous biosynthesis of abietane-type diterpenes.
Subject(s)
Diterpenes , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Abietanes , Acetyl Coenzyme A/metabolism , NADP/metabolism , Diterpenes/metabolism , Metabolic Engineering/methodsABSTRACT
OBJECTIVE: Due to heterogeneity and limited medical data in primary healthcare services (PHS), assessing the psychological risk of type 2 diabetes mellitus (T2DM) patients in PHS is difficult. Using unsupervised contrastive pre-training, we proposed a deep learning framework named depression and anxiety prediction (DAP) to predict depression and anxiety in T2DM patients. MATERIALS AND METHODS: The DAP model consists of two sub-models. Firstly, the pre-trained model of DAP used unlabeled discharge records of 85 085 T2DM patients from the First Affiliated Hospital of Nanjing Medical University for unsupervised contrastive learning on heterogeneous electronic health records (EHRs). Secondly, the fine-tuned model of DAP used case-control cohorts (17 491 patients) selected from 149 596 T2DM patients' EHRs in the Nanjing Health Information Platform (NHIP). The DAP model was validated in 1028 patients from PHS in NHIP. Evaluation included receiver operating characteristic area under the curve (ROC-AUC) and precision-recall area under the curve (PR-AUC), and decision curve analysis (DCA). RESULTS: The pre-training step allowed the DAP model to converge at a faster rate. The fine-tuned DAP model significantly outperformed the baseline models (logistic regression, extreme gradient boosting, and random forest) with ROC-AUC of 0.91±0.028 and PR-AUC of 0.80±0.067 in 10-fold internal validation, and with ROC-AUC of 0.75 ± 0.045 and PR-AUC of 0.47 ± 0.081 in external validation. The DCA indicate the clinical potential of the DAP model. CONCLUSION: The DAP model effectively predicted post-discharge depression and anxiety in T2DM patients from PHS, reducing data fragmentation and limitations. This study highlights the DAP model's potential for early detection and intervention in depression and anxiety, improving outcomes for diabetes patients.
Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Electronic Health Records , Aftercare , Depression , Machine Learning , Patient Discharge , AnxietyABSTRACT
Mitochondria, which are double-membrane bound organelles commonly found in eukaryotic cells, play a fundamental role as sites for cellular energy production. Within the mitochondria, there exist substructures called submitochondria, and specific proteins associated with submitochondria have been implicated in various human diseases. Therefore, comprehending the precise localization of these submitochondrial proteins is of utmost importance. Such knowledge not only aids in unraveling their role in the pathogenesis of diseases but also facilitates the development of therapeutic drugs and diagnostic methods. In this study, we proposed a novel method based on Gene Ontology (GO) to predict the localization of the submitochondrial proteins, called GO-Submito. More specifically, the GO-Submito fine-tuned pre-training Bidirectional Encoder Representations from Transformers models to encode GO annotations into vectors. Subsequently, the Multi-head Attention Mechanism was employed to fuse these encoded vectors of GO annotations, enabling precise localization prediction. Through comprehensive evaluation, our results demonstrated that GO-Submito outperforms existing methods, offering a reliable and efficient tool for precisely localizing submitochondrial proteins.
Subject(s)
Mitochondria , Proteins , Humans , Gene Ontology , Proteins/chemistry , Mitochondria/genetics , Mitochondria/metabolism , Molecular Sequence Annotation , Computational Biology/methodsABSTRACT
The development of autoclavable hydrogels has been driven by the need for materials that can withstand the rigors of sterilization without compromising their properties or functionality. Many conventional hydrogels cannot withstand autoclave treatment owing to the breakdown of their composition or structure under the high-temperature and high-pressure environment of autoclaving. Here, the effect of autoclaving on the physical, mechanical, and biological properties of bovine serum albumin methacryloyl (BSAMA) cryogels at three protein concentrations (3, 5, and 10%) was extensively studied. We found that BSAMA cryogels at three concentrations remained little changed after autoclaving in terms of gross shape, pore structure, and protein secondary structure. Young's modulus of autoclaved BSAMA cryogels (BSAMAA) at low concentrations (3 and 5%) was similar to that of BSAMA cryogels, whereas 10% BSAMAA exhibited a higher Young's modulus value, compared with 10% BSAMA. Interestingly, BSAMAA cryogels prolonged degradation. Importantly, cell viability, drug release, and hemolytic behaviors were found to be similar among the pre- and post-autoclaved cryogels. Above all, autoclaving proved to be more effective in sterilizing BSAMA cryogels from bacteria contamination than UV and ethanol treatments. Thus, autoclavable BSAMA cryogels with uncompromising properties would be useful for biomedical applications.
ABSTRACT
Drug combination therapies are promising clinical treatments for curing patients. However, efficiently identifying valid drug combinations remains challenging because the number of available drugs has increased rapidly. In this study, we proposed a deep learning model called the Dual Feature Fusion Network for Drug-Drug Synergy prediction (DFFNDDS) that utilizes a fine-tuned pretrained language model and dual feature fusion mechanism to predict synergistic drug combinations. The dual feature fusion mechanism fuses the drug features and cell line features at the bit-wise level and the vector-wise level. We demonstrated that DFFNDDS outperforms competitive methods and can serve as a reliable tool for identifying synergistic drug combinations.
ABSTRACT
Currently, aqueous zinc-ion batteries, with large reserves of zinc metal and maturity of production, are a promising alternative to sustainable energy storage. Nevertheless, aqueous solution has poor frost resistance and is prone to side reactions. In addition, zinc dendrites also limit the performance of zinc-ion batteries. Biomass, with complex molecular structure and abundant functional groups, makes it have great application prospects. In this review, the research progress of biomass and its derived materials used in zinc-ion batteries are reviewed. The different regulation strategies and characteristics of biomass used in zinc-ion battery electrodes, electrolyte separators and binders are demonstrated. The regulation mechanism is analyzed. At the end, the development prospect and challenges of biomass in energy materials application are proposed.
ABSTRACT
In recent years, metal-free catalysts for persulfate-mediated oxidation processes have been widely applied to remove contaminants in the aquatic environment. Herein, a simple pyrolysis approach was used to synthesize the boron doped biochars (B@TBCs) derived from boric acid mixed with tea seed shells powders. The obtained B@TBCs exhibited fantastic capability to boost PMS (0.5 mM) activation for 90%â¼ removal of oxytetracycline (OTC) within 20 min. Through the correlation analysis and DFT calculations, it was concluded that the apparent rate constant of pollutants removal was greatly related to the -O-B-O- groups on the biochars, which could improve the electron-donating capacity of the biochar. In addition, the degradation process of OTC was pH-dependent because of the changed roles of ROSs under different pH. Finally, according to the DFT calculation, LC-MS and toxicological analysis, the degradation pathways of pollutants and the toxicity changes during the degradation process were obtained. These findings consolidated the theoretical basis for further boosting the catalytic activity of B-doped biochars and expanded the imagination for the modification of other metal-free biochar catalysts for PMS activation.
Subject(s)
Environmental Pollutants , Oxytetracycline , Boron , Charcoal , Metals , PeroxidesABSTRACT
A crucial method for adding new functions to current biomaterials for biomedical applications has been surface functionalization via molecular design. Mussel-inspired polydopamine (PDA) has generated much attention as a facile method for the functionalization of biomaterials because of its substantial independence in deposition, beneficial cell interactions, and significant responsiveness aimed at secondary functionalization. Because of their porous structure, the bovine serum albumin methacryloyl (BSAMA)-BM cryogels were functionalized with PDA (BM-PDA), which may reproduce the architecture and biological purpose of the natural extracellular environment. Excellent antioxidative and antibacterial qualities, improved mineralization, and better cell responsiveness were all demonstrated by BM-PDA. BM-PDA scaffolds maintained their linked and uniform pores after functionalization, which can make it easier for nutrients to be transported during bone repair. As a result, hydroxyapatite (HA)-coated BM* and BM-PDA* cryogels were created through successive mineralization with the goal of mineralized bone tissue repair. The heterogeneous nucleation and surface roughness contributed to rod-like apatite production in BM-PDA* cryogels whereas BM* cryogels were made up of plate-like HA morphologies. Analysis results showed that after five cycles, the mineral contents were around 57% and the HA units remained equally dispersed on the surface of BM-PDA* with a Ca/P ratio of 1.63. Other natural polymer-based cryogels can be coated using this general, rapid, and simple PDA coating technique and utilized as implants for bone tissue engineering. Future clinical uses of albumin cryogels for bone tissue engineering will advance as a result of additional in-vivo testing of such PDA-coated cryogels.
ABSTRACT
MOTIVATION: The capability to predict the potential drug binding affinity against a protein target has always been a fundamental challenge in silico drug discovery. The traditional experiments in vitro and in vivo are costly and time-consuming which need to search over large compound space. Recent years have witnessed significant success on deep learning-based models for drug-target binding affinity prediction task. RESULTS: Following the recent success of the Transformer model, we propose a multigranularity protein-ligand interaction (MGPLI) model, which adopts the Transformer encoders to represent the character-level features and fragment-level features, modeling the possible interaction between residues and atoms or their segments. In addition, we use the convolutional neural network to extract higher-level features based on transformer encoder outputs and a highway layer to fuse the protein and drug features. We evaluate MGPLI on different protein-ligand interaction datasets and show the improvement of prediction performance compared to state-of-the-art baselines. AVAILABILITY AND IMPLEMENTATION: The model scripts are available at https://github.com/IILab-Resource/MGDTA.git.
Subject(s)
Neural Networks, Computer , Proteins , Ligands , Proteins/chemistry , Drug DiscoveryABSTRACT
For porous protein scaffolds to be employed in tissue-engineered structures, the development of cost-effective, macroporous, and mechanically improved protein-based hydrogels, without compromising the original properties of native protein, is crucial. Here, we introduced a facile method of albumin methacryloyl transparent hydrogels and opaque cryogels with adjustable porosity and improved mechanical characteristics via controlling polymerization temperatures (room temperature and -80 °C). The structural, morphological, mechanical, and physical characteristics of both porous albumin methacryloyl biomaterials were investigated using FTIR, CD, SEM, XRD, compression tests, TGA, and swelling behavior. The biodegradation and biocompatibility of the various gels were also carefully examined. Albumin methacryloyl opaque cryogels outperformed their counterpart transparent hydrogels in terms of mechanical characteristics and interconnecting macropores. Both materials demonstrated high mineralization potential as well as good cell compatibility. The solvation and phase separation owing to ice crystal formation during polymerization are attributed to the transparency of hydrogels and opacity of cryogels, respectively, suggesting that two fully protein-based hydrogels could be used as visible detectors/sensors in medical devices or bone regeneration scaffolds in the future.
ABSTRACT
Immobilized microorganism technology has attracted increasing attention for high concentration of microbes, low cell loss and high resistance to impact of environment. The microbial reduction of nitrate in the presence of sediment-based biochar (SBC) and nanoscale zero-valent iron (nZVI) was investigated in four different free systems. NZVI-SBC/bacteria system realized the best nitrate removal of 97.61% within 3 days through the synergistic effect of SBC and nZVI on denitrifying bacteria. Accumulation of nitrite and ammonium in nZVI-SBC/bacteria system also decreased. High-throughput sequencing results showed that the proportion of denitrifying bacteria in microbial community structure increased after adding nZVI-SBC. The performance of nitrate removal was then studied through PVA/SA-immobilization. Immobilized active pellets performed better nitrate removal (98.89%) and stronger tolerance under different conditions than the free bacterial cells. Overall, this study provided a promising approach by utilizing SBC and nZVI for the bio-remediation of nitrate-contaminated water in practical application.
Subject(s)
Nitrates , Water Pollutants, Chemical , Charcoal , Iron , Nitrogen Oxides , Water Pollutants, Chemical/analysisABSTRACT
In this study, inspired by nacre-like structural natural shells, novel three-dimensional (3D) nanocomposites based on natural nanoplatelets of montmorillonite (MMT) and polysaccharide of chitosan (CS) were prepared with solution intercalation and self-assembly process. The CS-intercalated-MMT nanoplatelets units acted as "bricks" and CS molecules acted as "mortar", arranging in fairly well-ordered layered structure. With addition of glutaraldehyde (GA) and Pd2+ cations, synergistic toughening and strengthening effects of covalent and ionic bonds could be achieved. The best mechanical properties of the prepared 3D nanocomposites were observed as 5.6 KJ/m2 (impact strength), 3.3 GPa (flexural modulus), and 65.8 MPa (flexural strength), respectively, which showed higher toughness but lower flexural properties than natural pearl mussel shells. Nevertheless, both the impact and flexural properties of the prepared 3D nanocomposite were much higher than the other natural shell, i.e. green grab shell. Besides conventional methods characterizations, the nacre-like structure of the artificial 3D nanocomposite was further evidenced with positron annihilation lifetime spectroscopy characterizations. This work might facilitate a versatile platform for developing green 3D bionanocomposites with fairly good mechanical properties.
Subject(s)
Bentonite/chemistry , Chitosan/chemistry , Nanocomposites/chemistry , Glutaral/chemistry , X-Ray DiffractionABSTRACT
Membranous obstruction of the inferior vena cava (MOVC) has the highest incidence rate among the different types of BuddChiari syndrome (BCS) in China. The inferior vena cava septum of patients with MOVC contains capillaries and the two surfaces of the membrane are composed of vascular endothelial tissue. Membrane formation occurs due to endothelial damage. MicroRNAs (miRNAs/miRs) have been verified to be involved in the pathogenesis and progression of various human diseases. A previous study by our group suggested that miR3133 was downregulated in the serum of patients with MOVC. In the present study, the possible mechanistic implication of miR3133 in MOVCassociated processes was further explored. It was observed that miR3133 overexpression inhibited, whereas miR3133 knockdown enhanced the proliferation and tube formation of human umbilical vein endothelial cells (HUVECs) using the CCK8 and tube formation assays. JUNB, a member of activator protein 1 and an important upstream transcriptional molecule of vascular endothelial growth factor (VEGF), was proven to be a direct target gene of miR3133 using a bioinformatics prediction and luciferase reporter assay. Meanwhile, the mRNA and protein expression of JUNB and VEGF was determined by PCR, ELISA and western blot analyses. Of note, miR3133 overexpression downregulated, while miR3133 knockdown elevated the expression of JUNB and VEGF significantly. Furthermore, it was demonstrated that JUNB upregulated the expression and secretion of VEGF to promote HUVEC proliferation and angiogenesis. miR3133 was able to inhibit the effect of JUNB overexpression to promote cell proliferation, angiogenesis and the expression of VEGF. In conclusion, the present study demonstrated that miR3133 regulated endothelial cell proliferation and angiogenesis through the JUNB/VEGF pathway, which may provide an approach for inhibiting diaphragm formation of the inferior vena cava in MOVC.
Subject(s)
MicroRNAs/genetics , Neovascularization, Pathologic/genetics , Transcription Factors/genetics , Vascular Endothelial Growth Factor A/genetics , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Human Umbilical Vein Endothelial Cells , Humans , Neovascularization, Pathologic/pathology , Proto-Oncogene Proteins c-akt/genetics , Signal Transduction/geneticsABSTRACT
Biopolymer of chitosan (CS) and titanium pillared clays (Ti-PILCs) have been combined in a hybrid as advanced supports for immobilization of PdOx=0,1 species to prepare novel PdOx=0,1@Ti-PILC/CS nano-composite catalysts. The Ti-PILC materials showed high specific surface areas and abundant meso-porous structure with many irregular pore channels caused by collapses of layered structure of clay during Ti pillaring process. Both CS chains and sub-nano sized PdOx particles were successfully incorporated into the pore channels of Ti-PILC, resulting in a decrease in both the specific surface areas and uniform distribution of pore size. Besides conventional methods characterizations, the strong interactions between PdOx species and Ti-PILC/CS support were further evidenced with positron annihilation lifetime spectroscopy studies. The resultant PdOx@Ti-PILC/CS catalyst was highly active for the coupling reactions of aryl halides with phenyl acetylenes. It was recyclable and gave excellent yield up to 13 runs with low leaching of Pd species.
ABSTRACT
Novel porous chitosan/reduced graphene oxide microspheres supported Pd nanoparticles catalysts (Pd@CS/RGO) were prepared by a combination of silica nanoparticles etching and freeze-drying treatments of CS/RGO/silica/PdCl2 composite microspheres. The microstructure of the Pd@CS/RGO microspheres catalysts have been investigated by X-ray photo electron spectroscopy (XPS), Raman spectroscopy, high resolution transmission electron microscopy (HR-TEM), thermo-gravimetric analysis (TGA), and X-ray diffraction (XRD), etc. The results revealed that: the novel catalysts showed open porous structure; CS had good miscibility with RGO nanosheets; Pd nanoparticles were well incorporated within CS/RGO matrix; the thermal stabilities of the catalysts were improved significantly over CS. Meanwhile, the Pd@CS/RGO catalysts have been demonstrated as highly active and easily recyclable catalysts for Heck reactions. The preparation process is simple, and the structure and performance of the catalytic material can be governed by changing the mass ratios of CS/RGO/silica/PdCl2 and the pore-forming process conditions.
ABSTRACT
In this study, montmorillonite (MMT) was modified by intercalating polyethylene oxide (PEO) macromolecules between the interlayer spaces in an MMT-water suspension system. X-ray diffraction results revealed that the galleries of MMT were expanded significantly after intercalation of different loading of PEO. MMT/PEO 80/20 composite was chosen as the support platform for immobilization of Pd species in preparing novel heterogeneous catalysts. After immobilization of Pd species, the interlayer spacing of MMT/PEO (80/20) (1.52 nm) was further increased to 1.72 nm (Pd2+@MMT/PEO) and 1.73 nm (Pd0@MMT/PEO), confirming the well-immobilization of the Pd species in the interlayer spaces of PEO-modified MMT. High-resolution transmission electron microscopy (HR-TEM) observation results confirmed that Pd nanoparticles were confined inside the interlayer space of MMT and/or dispersed well on the outer surface of MMT. The conversion of Pd2+ to Pd0 species was evidenced by binding energy characterization with X-ray photo electron spectroscopy (XPS). The microstructure variation caused by the Pd immobilization was sensitively detected by positron annihilation lifetime spectroscopy (PALS) studies. The prepared Pd0@MMT/PEO (0.2/80/20) catalytic composite exhibits good thermal stability up to around 200 °C, and it showed high activities for Heck reactions between aryl iodides and butyl acrylates and could be recycled for five times. The correlations between the microstructure and properties of the Pd@MMT/PEO catalytic composites were discussed.
ABSTRACT
Novel porous nitrogen-doped carbon supported Pd (Pd@N-C) catalytic composites were prepared by one-pot thermal carbonization of chitosan/poly(ethylene glycol)blockpoly(propylene glycol)blockpoly(ethylene glycol)/PdCl2 (CS/P123/PdCl2) blend hydrogel membranes at different temperature in N2 atmosphere. The porous structure of the Pd@N-C catalytic composite was governed by both the addition of P123 and the carbonization temperature. At highest carbonization temperature of 900⯰C, the prepared Pd@N-C catalytic composite from CS/P123/PdCl2 blend membrane showed the highest specific area (SBET) of 293.7â¯m2/g and total volume of pores (Vtot) of 0.79â¯cm3/g. The chemical state of the elements of C, N, O, Pd within the Pd@N-C catalytic composites were confirmed with X-ray photoelectron spectroscopy (XPS) measurements. Raman spectrum results showed that the prepared Pd@N-C catalytic composite contained mainly disordered carbon together with some graphite carbon. Pd nanoparticles sized in 5-20â¯nm dispersed well on the porous matrix of the carbon. The Pd@N-C catalytic composites showed excellent activities for the Ullmann homo-coupling reactions of aromatic halides, and can be recycled for 10 times. In such one-pot carbonization process, the polymer porogen is simultaneously decomposed without further etching and removal steps, which simplifies the preparation process and is beneficial to obtain Pd@N-C catalytic composites with desirable Pd loading.
Subject(s)
Carbon/chemistry , Chitosan/chemistry , Hydrogels/chemistry , Palladium/chemistry , Phosphatidylethanolamines/chemistry , Catalysis , Oxidative Coupling , Spectrum AnalysisABSTRACT
AIMS: Angiogenesis is associated with the progression and mortality of gastric cancer. Epidemiological evidences indicate that long-term N-nitroso compounds (NOCs) exposure predominantly contributes to the mortality of gastric cancer. Therefore, further reduced mortality of gastric cancer demands to explore the exact mechanisms of NOCs induced angiogenesis. As a tumor suppressor gene, inhibitor of growth protein 4 (ING4) plays an important role in pathological angiogenesis. In this study, we will investigate ING4 expression level in human gastric epithelial cells after the long-term low dose exposure of N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and the pathological impact of MNNG-reduced ING4 on angiogenesis of transformed cells. MAIN METHODS: The soft agar colony formation assay, Western blotting, immunofluorescence and wound healing assay were used to evaluate the characteristics of transformed cells. HUVEC growth and tube formation assays were performed to test the angiogenic abilities. EMSA, luciferase reporter gene assay, real-time PCR and Western blotting were used to explore the exact mechanism. KEY FINDINGS: By establishing transformed human gastric epithelial cells via chronic low dose treatment, a gradually ING4 downregulation was observed in the later-stage of MNNG-induced cell transformation. Moreover, we demonstrated that MNNG exposure-reduced ING4 expression significantly resulted into aggravating angiogenesis through increasing the phosphorylation level of NF-κB p65 and subsequently DAN binding activity and regulating the expressions of NF-κB p65 downstream pro-angiogenic genes, MMP-2 and MMP-9. SIGNIFICANCE: Our findings provided a significant mechanistic insight into angiogenesis of MNNG-transformed human gastric epithelial cell and supported the concept that ING4 may be a relevant therapeutic target for gastric cancer.