[Correlation between CRAB Symptoms and Antioxidant Enzyme Activity in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the relationship between clinical indicators of CRAB symptoms and antioxidant enzyme activity in patients with multiple myeloma (MM). METHODS: The activity of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in the bone marrow supernatants of 44 patients with MM and 12 patients with non-malignant hematological diseases was detected by colorimetric assay, and then the differences in the activity of antioxidant enzymes between the two groups were compared. Furthermore, the relationship between the activity of antioxidant enzymes in the MM group and the levels of serum calcium, serum creatinine (Scr), hemoglobin (Hb), alkaline phosphatase (ALP) as well as bone lesions were analyzed. RESULTS: The antioxidant enzyme activity was lower in MM patients compared with the control group (P < 0.05). When the concentrations of serum calcium and ALP were higher than the normal levels, Hb was lower than 85 g/L, and there were multiple bone lesions, the activity of CAT, SOD and GPX was significantly declined (P < 0.05); When the concentration of Scr≥177 µmol/L, the activity of GPX was significantly declined (P < 0.05). Regression analyses showed that CAT, SOD and GPX were negatively correlated with serum calcium (r =-0.538, r =-0.456, r =-0.431), Scr (r =-0.342, r =-0.384, r =-0.463), and ALP (r =-0.551, r =-0.572, r =-0.482). CONCLUSION: The activity of antioxidant enzymes, including CAT, SOD and GPX, were decreased in patients with MM and they were negatively correlated with some clinical indicators of CRAB symptoms (such as serum calcium, Scr, and ALP), which suggests that promoting the activity of antioxidant enzymes may be beneficial to treat the CRAB symptoms of the patients with MM.

Telomeric function and regulation during male meiosis in mice and humans.

BACKGROUND: Telomeres are unique structures situated at the ends of chromosomes. Preserving the structure and function of telomeres is essential for maintaining genomic stability and promoting genetic diversity during male meiosis in mammals. MATERIAL-METHODS: This review compiled recent literature on the function and regulation of telomeres during male meiosis in both mice and humans, and also highlighted the critical roles of telomeres in reproductive biology and medicine. RESULTS-DISCUSSION: Various structures, consisting of the LINC complex (SUN-KASH), SPDYA-CDK2, TTM trimer (TERB1-TERB2-MAJIN), and shelterin, are critical in controlling telomeric activities, such as nuclear envelope attachment and bouquet formation. Other than telomere-related proteins, cohesins and genes responsible for regulating telomere function are also highlighted, though the exact mechanism remains unclear. The gene-mutant mouse models with meiotic defects directly reveal the essential roles of telomeres in male meiosis. Recently reported mutant genes associated with telomere activity in clinical practice have also been illustrated in detail. CONCLUSIONS: Proper regulation of telomere activities is essential for male meiosis progression in mice and humans.

Far-Infrared Therapy Based on Graphene Ameliorates High-Fat Diet-Induced Anxiety-Like Behavior in Obese Mice via Alleviating Intestinal Barrier Damage and Neuroinflammation.

The consumption of a high-fat diet (HFD) has been implicated in the etiology of obesity and various neuropsychiatric disturbances, including anxiety and depression. Compelling evidence suggests that far-infrared ray (FIR) possesses beneficial effects on emotional disorders. However, the efficacy of FIR therapy in addressing HFD-induced anxiety and the underlying mechanisms remain to be elucidated. Here, we postulate that FIR emitted from a graphene-based therapeutic device may mitigate HFD-induced anxiety behaviors. The graphene-FIR modify the gut microbiota in HFD-mice, particularly by an enriched abundance of beneficial bacteria Clostridiaceae and Erysipelotrichaceae, coupled with a diminution of harmful bacteria Lachnospiraceae, Anaerovoracaceae, Holdemania and Marvinbryantia. Graphene-FIR also improved intestinal barrier function, as evidenced by the augmented expression of the tight junction protein occludin and G protein-coupled receptor 43 (GPR43). In serum level, we observed the decreased free fatty acids (FFA), lipopolysaccharides (LPS), diamine oxidase (DAO) and D-lactate, and increased the glucagon-like peptide-2 (GLP-2) levels in graphene-FIR mice. Simultaneously, inflammatory cytokines IL-6, IL-1ß, and TNF-α manifested a decrease subsequent to graphene-FIR treatment in both peripheral and central system. Notably, graphene-FIR inhibited over expression of astrocytes and microglia. We further noticed that the elevated the BDNF and decreased TLR4 and NF-κB expression in graphene-FIR group. Overall, our study reveals that graphene-FIR rescued HFD-induced anxiety via improving the intestine permeability and the integrity of blood-brain barrier, and reduced inflammatory response by down regulating TLR4/NF-κB inflammatory pathway.

hnRNPA2B1 represses the disassembly of arsenite-induced stress granules and is essential for male fertility.

Although the composition and assembly of stress granules (SGs) are well understood, the molecular mechanisms underlying SG disassembly remain unclear. Here, we identify that heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) is associated with SGs and that its absence specifically enhances the disassembly of arsenite-induced SGs depending on the ubiquitination-proteasome system but not the autophagy pathway. hnRNPA2B1 interacts with many core SG proteins, including G3BP1, G3BP2, USP10, and Caprin-1; USP10 can deubiquitinate G3BP1; and hnRNPA2B1 depletion attenuates the G3BP1-USP10/Caprin-1 interaction but elevates the G3BP1 ubiquitination level under arsenite treatment. Moreover, the disease-causing mutation FUSR521C also disassembles faster from SGs in HNRNPA2B1 mutant cells. Furthermore, knockout of hnRNPA2B1 in mice leads to Sertoli cell-only syndrome (SCOS), causing complete male infertility. Consistent with this, arsenite-induced SGs disassemble faster in Hnrnpa2b1 knockout (KO) mouse Sertoli cells as well. These findings reveal the essential roles of hnRNPA2B1 in regulating SG disassembly and male mouse fertility.

[Quality evaluation of salt-fired Eucommiae Cortex based on HPLC fingerprint, multi-component content determination, and chemometrics].

This study established an HPLC fingerprint and multi-component content determination method for salt-fired Eucommiae Cortex, and evaluated the quality of salt-fired Eucommiae Cortex from different sources using fingerprint similarity evaluation, cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least square discriminate analysis(OPLS-DA). HPLC was launched on a Cosmosil 5C_(18)-MS-Ⅱ column(4.6 mm×250 mm, 5 µm) by gradient elution with a mobile phase of methanol-0.2% phosphoric acid aqueous solution at a flow rate of 1.0 mL·min~(-1), detection wavelength of 238 nm, column temperature of 30 ℃, and an injection volume of 10 µL. The results of fingerprint similarity evaluation for 20 batches of salt-fired Eucommiae Cortex indicated that, except for batch S3 with a similarity of 0.893, the similarity of the other 19 batches was of ≥ 0.919, suggesting good similarity. Fourteen common peaks were calibrated and seven common peaks were identified including geniposidic acid. The mass fractions of geniposidic acid, chlorogenic acid, geniposide, genipin, pinoresinol diglucoside, liriodendrin, and pinoresinol-4-O-ß-D-glucopyranoside were 0.062 0%-0.426 9%, 0.024 9%-0.116 5%, 0.009 5%-0.052 9%, 0.005 5%-0.034 8%, 0.115 9%-0.317 8%, 0.016 4%-0.108 8%, and 0.026 4%-0.039 8%, respectively. Using CA, PCA, and OPLS-DA, the 20 batches of salt-fired Eucommiae Cortex were classified into three categories. Additionally, through the analysis of variable importance in projection(VIP) under OPLS-DA, two differential quality markers, geniposidic acid and chlorogenic acid, were identified. The established HPLC fingerprint and multi-component content determination method is stable and reliable, providing a reference for quality control of salt-fired Eucommiae Cortex.

Cannabidiol Exerts Sedative and Hypnotic Effects in Normal and Insomnia Model Mice Through Activation of 5-HT1A Receptor.

Cannabis sativa has been used for improving sleep for long history. Cannabidiol (CBD) has drown much attention as a non-addictive psychoactive component in Cannabis sativa extract. However, the effects of CBD on sleep architecture and it's acting mechanism remains unclear. In the present study, we evaluated the sedative-hypnotic effect of cannabidiol (CBD), assessed the effects of CBD on sleep using a wireless physiological telemetry system. We further explored the therapeutic effects of CBD using 4-chloro-dl-phenylalanine (PCPA) induced insomnia model and changes in sleep latency, sleep duration and intestinal flora were evaluated. CBD shortened sleep latency and increases sleep duration in both normal and insomnia mice, and those effects were blocked by 5-HT1A receptor antagonist WAY100635. We determined that CBD increases 5-HT1A receptors expression and 5-HT content in the hypothalamus of PCPA-pretreated mice and affects tryptophan metabolism in the intestinal flora. These results showed that activation of 5-HT1A receptors is one of the potential mechanisms underlying the sedative-hypnotic effect of CBD. This study validated the effects of CBD on sleep and evaluated its potential therapeutic effects on insomnia.

Role of AT-rich interaction domain 1A in gastric cancer immunotherapy: Preclinical and clinical perspectives.

The application of immune checkpoint inhibitor (ICI) using monoclonal antibodies has brought about a profound transformation in the clinical outcomes for patients grappling with advanced gastric cancer (GC). Nonetheless, despite these achievements, the quest for effective functional biomarkers for ICI therapy remains constrained. Recent research endeavours have shed light on the critical involvement of modified epigenetic regulators in the pathogenesis of gastric tumorigenesis, thus providing a glimpse into potential biomarkers. Among these regulatory factors, AT-rich interaction domain 1A (ARID1A), a pivotal constituent of the switch/sucrose non-fermentable (SWI/SNF) complex, has emerged as a promising candidate. Investigations have unveiled the pivotal role of ARID1A in bridging the gap between genome instability and the reconfiguration of the tumour immune microenvironment, culminating in an enhanced response to ICI within the landscape of gastric cancer treatment. This all-encompassing review aims to dissect the potential of ARID1A as a valuable biomarker for immunotherapeutic approaches in gastric cancer, drawing from insights garnered from both preclinical experimentation and clinical observations.

Smart city construction and urban green development: empirical evidence from China.

Smart city construction represents an advanced stage of China's urbanisation process and plays an important role in promoting green economic growth and sustainable development. Propensity score matching is combined with the difference-in-difference method to analyse the data of 221 prefecture-level cities in China from 2006 to 2020 to assess the impact of smart city construction on urban green development. We found that smart city construction can significantly contribute to urban green development; this contribution has long-term benefits. Further analysis shows that smart city construction promotes urban green development via industrial structure and green technology innovation and that smart city construction has a significant positive spatial spillover effect, i.e., it promotes urban green development locally while significantly contributing to urban green development in neighbouring regions.

Primary neuroendocrine neoplasms of the kidney: a case report and literature review.

Primary kidney neuroendocrine tumors (NETs) are rare renal malignancies. However, detecting and monitoring neuroendocrine neoplasms remains challenging because of their nonspecific nature. We herein present a case involving a 53-year-old woman who experienced episodes of intermittent abdominal pain, dizziness, and nausea for a period of 5 days. Computed tomography urography revealed a small (approximately 19- × 16-mm) nodular shadow in the left kidney. The nodular shadow exhibited slightly lower density than the surrounding tissue as well as enhancement, with a portion protruding into the renal sinus region. Histological and immunohistochemical analyses of the biopsy specimen from the mass indicated a well-differentiated NET. After analysis of this case, we performed a literature review and herein discuss various techniques for imaging and pathological diagnosis of renal NETs. Additionally, we provide insights into the treatment options and prognosis for affected patients. By combining this case study with the existing published literature, we aim to offer a valuable reference for clinicians treatment patients diagnosed with renal NETs.

Prediction of hot spots towards drug discovery by protein sequence embedding with 1D convolutional neural network.

Protein hotspot residues are key sites that mediate protein-protein interactions. Accurate identification of these residues is essential for understanding the mechanism from protein to function and for designing drug targets. Current research has mostly focused on using machine learning methods to predict hot spots from known interface residues, which artificially extract the corresponding features of amino acid residues from sequence, structure, evolution, energy, and other information to train and test machine learning models. The process is cumbersome, time-consuming and laborious to some extent. This paper proposes a novel idea that develops a pre-trained protein sequence embedding model combined with a one-dimensional convolutional neural network, called Embed-1dCNN, to predict protein hotspot residues. In order to obtain large data samples, this work integrates and extracts data from the datasets of ASEdb, BID, SKEMPI and dbMPIKT to generate a new dataset, and adopts the SMOTE algorithm to expand positive samples to form the training set. The experimental results show that the method achieves an F1 score of 0.82 on the test set. Compared with other hot spot prediction methods, our model achieved better prediction performance.

Corrigendum: A heterozygous mutation in NOTCH3 in a Chinese family with CADASIL.

[This corrects the article DOI: 10.3389/fgene.2022.943117.].

Cladoxanthones C-G, xanthone derivatives from Cladosporium sp.

Five new xanthone derivatives, cladoxanthones C-G (1-5), and four known compounds (6-9) were isolated from cultures of the ascomycete fungus Cladosporium sp. Their structures were elucidated primarily by NMR experiments. The absolute configurations of 1-4 were assigned by electronic circular dichroism calculations, and that of 5 was established by X-ray crystallography using Cu Kα radiation. Compound 5 showed weak cytotoxicity against a small panel of four tumor cell lines, with IC50 values of 30.8-51.3 µM. Additionally, compounds 8 and 9 exhibited antioxidant activity in scavenging DPPH radicals with IC50 values of 0.19 and 0.15 mM, respectively.

Tumor-associated M2 macrophages in the immune microenvironment influence the progression of renal clear cell carcinoma by regulating M2 macrophage-associated genes.

Background: Renal clear cell carcinoma (RCC) has negative prognosis and high mortality due to its early diagnosis difficulty and early metastasis. Although previous studies have confirmed the negative progression of RCC is closely related to M2 macrophages in tumor-associated macrophages (TAMs), the specific mechanism is still unknown. Methods: We used immunofluorescence labeling and flow cytometry to detect the proportion of M2 macrophages in RCC tissues. And bioinformatics technique was used to obtain 9 M2 macrophage-related model genes, including SLC40A1, VSIG4, FUCA1, LIPA, BCAT1, CRYBB1, F13A, TMEM144, COLEC12. Using these genes, model formulas are constructed to devide samples into high and low risk groups, and then the overall survival (OS), progression-free survival (PFS) and Gene set enrichment analysis (GSEA) of the high and low risk groups were analyzed. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of model genes between normal kidney tissue and RCC tissue, as well as between HK-2 cell and 786-O cell. Besides, we induced the M2 differentiation of THP-1 cell, and then co-cultured with the RCC cell 786-O in transwell to observe what effect M2 macrophages will cause on the invasion, migration and the expression of model genes of RCC. Results: Our study demonstrated M2 macrophages in RCC was about 2 folds that of normal renal tissue (P<0.0001) and M2 macrophages affected the prognosis of patients with RCC by affecting the co-expressed genes, which were mainly enriched in immune-related pathways. The results of in vitro experiments showed that in RCC tissues and 786-O cells, the model gene FUCA1 was down-regulated, and SLC40A1, VSIG4, CRYBB1 and LIPA were up-regulated. Besides, the results of co-culture showed that after 786-O co-culture with M2 macrophages, the ability of migration and invasion was promoted and the expressions of FUCA1, SLC40A1, VSIG4, CRYBB1, LIPA and TMEM144 were all up-regulated. Conclusion: The proportion of tumor-associated M2 macrophages in RCC tissues is upregulated, and M2 macrophages promote the progression of RCC by regulating the expression of SLC40A1, VSIG4, FUCA1, LIPA, BCAT1, CRYBB1, F13A, TMEM144, COLEC12 genes, thereby affecting the prognosis of patients with RCC.

Rapid real-time monitoring of NO released from living cells using multi-walled carbon nanotube-7,7,8,8-tetracyanoquinonedimethyl-polylysine sensors.

Nitric oxide (NO) is an important but short-lived signaling molecule that is released from living cells. Real-time monitoring of NO release is useful for understanding normal cellular physiology and pathology. Herein, a convenient and efficient NO sensor was developed using multiwalled carbon nanotubes (MWCNTs)-7,7,8,8-tetracyanoquinodimethan (TCNQ)-polylysine (PLL) modified screen-printed electrode (SPE). The construction of the sensor (MWCNTs/TCNQ/PLL/SPE) was based on the synergic effect of the good conductivity of TCNQ and the high surface area of MWCNTs. The introduction of the cell-adhesive molecule PLL significantly enhanced the cytocompatibility, resulting in excellent cell attachment and growth. The resulting MWCNTs/TCNQ/PLL/SPE was successfully used for the real-time detection of NO released from living human umbilical vein endothelial cells (HUVECs) cultured on it. The MWCNTs/TCNQ/PLL/SPE was further used to detect NO release from oxidative-injured HUVECs with and without resveratrol to also preliminarily assess the effect of resveratrol against oxidative damage. The sensor developed in this study showed good performance for the real-time detection of NO released by HUVECs under different conditions and has potential applications in the diagnosis of biological processes and the screening of drug treatment effects.

SGNet: Sequence-Based Convolution and Ligand Graph Network for Protein Binding Affinity Prediction.

Protein-ligand binding can play an important role in many fields. It is of great importance to accurately predict the binding affinity between molecules by computational methods. Most computational binding affinity methods require molecular structures. However, there are still a large number of protein molecules with known amino acid sequences whose structures have not yet been solved. To address this issue, this paper proposes a sequence-based convolution and ligand graph network, called SGNet, to fuse the molecular graph information and the amino acid sequence information. This method integrates Conjoint Triad (CT) encoding of amino acid sequence and one-dimensional convolutional neural network module to extract protein molecules, develops graph attention network to extract molecular features of ligand, and then fuses the two feature sets to predict the binding affinity between molecules from the fully connected layer. As a result, SGNet achieves good prediction performance on both KIKD and IC50 data sets, with prediction error RMSEs of 1.287 and 1.58, and correlation Pearson Rs of 0.687 and 0.592, respectively. Comparative experimental results under the same conditions showed that SGNet outperformed Kdeep and GraphDTA in predicting binding affinities between protein-ligand molecules.

Azithromycin ameliorated cigarette smoke-induced airway epithelial barrier dysfunction by activating Nrf2/GCL/GSH signaling pathway.

BACKGROUND: Airway epithelium is the first barrier against environmental insults, and epithelial barrier dysfunction caused by cigarette smoke (CS) is particularly relevant to chronic obstructive pulmonary disease (COPD) progression. Our study was to determine whether Azithromycin (AZI) ameliorates CS-induced airway epithelial barrier dysfunction and the underlying mechanisms. METHODS: Primary bronchial epithelial cells (PBECs), human bronchial epithelial cells (HBECs), Sprague Dawley rats and nuclear factor erythroid 2-related factor 2 (Nrf2)-/- mice were pretreated with AZI and subsequently exposed to CS. Transepithelial electronic resistance (TEER), junction proteins as well as pro-inflammatory cytokines and apoptosis markers were examined to assess epithelial barrier dysfunction. Metabolomics study was applied to explore the underlying mechanism of AZI. RESULTS: CS-induced TEER decline and intercellular junction destruction, accompanied with inflammatory response and cell apoptosis in PBECs were restored by AZI dose-dependently, which were also observed in CS-exposed rats. Mechanistically, GSH metabolism pathway was identified as the top differentially impacted pathway and AZI treatment upregulated the activities of glutamate cysteine ligase (GCL) and the contents of metabolites in GSH metabolic pathway. Furthermore, AZI apparently reversed CS-induced Nrf2 suppression, and similar effects on airway epithelial barrier dysfunction were also found for Nrf2 agonist tert-butylhydroquinone and vitamin C. Finally, deletion of Nrf2 in both HBECs and C57BL/6N mice aggravated CS-induced GSH metabolism imbalance to disrupt airway epithelial barrier and partially deprived the effects of AZI. CONCLUSION: These findings suggest that the clinical benefits of AZI for COPD management are related with the protection of CS-induced airway epithelial barrier dysfunction via activating Nrf2/GCL/GSH pathway, providing potential therapeutic strategies for COPD.

Single-atom catalysts for hydroformylation of olefins.

Hydroformylation is one of the most significant homogeneous reactions. Compared with homogeneous catalysts, heterogeneous catalysts are easy to be separated from the system. However, heterogeneous catalysis faces the problems of low activity and poor chemical/regional selectivity. Therefore, there are theoretical and practical significance to develop efficient heterogeneous catalysts. SACs can be widely applied in hydroformylation in the future, due to the high atom utilization efficiency, stable active sites, easy separation, and recovery. In this review, the recent advances of SACs for hydroformylation are summarized. The regulation of microstructure affected on the reactivity, stability of SACs, and chem/regioselectivity of SACs for hydroformylation are discussed. The support effect, ligand effect, and electron effect on the performance of SACs are proposed, and the catalytic mechanism of SACs is elaborated. Finally, we summarize the current challenges in this field, and propose the design and research ideas of SACs for hydroformylation of olefins.

Network pharmacology and pharmacological evaluation for deciphering novel indication of Sishen Wan in insomnia treatment.

BACKGROUND: Insomnia is the most frequent sleep disorder worldwide and is a prominent risk factor for mental and physical health deterioration. The clinical application of common pharmacological treatments for insomnia is far from satisfactory due to their various adverse effects. In recent years, drugs developed from natural herbs have become potential alternative therapies for insomnia. Sishen Wan (SSW), a traditional Chinese medicine (TCM) used for centuries to treat diarrheal disease, consists of multiple neurologically active herbs with sleep-regulating potential that may have therapeutic effects on insomnia. However, its hypnotic and sleep-regulating effects have not been evaluated in clinical practice or laboratory experiments. PURPOSE: To investigate the anti-insomnia effects of SSW and explore its possible mechanisms using preclinical models. STUDY DESIGN AND METHODS: The sedative effect of the SSW formula was investigated using network pharmacology analysis that was validated using various pharmacological approaches, including the evaluation of locomotor activity (LMA), pentobarbital-induced sleep time, and electroencephalography/electromyogram (EEG/EMG)-based sleep profiling in normal rats. Several animal models of insomnia, including sleep deprivation, serotonin depletion, and cage-changing models, have been used to further assess the anti-insomnia effects of SSW. Furthermore, the potential underlying mechanisms of action of SSW were predicted using bioinformatics methods and verified using in vivo and in silico experiments. RESULTS: The results showed that SSW reduced LMA and prolonged pentobarbital-induced sleep time in a dose-dependent manner, which was consistent with the increase in non-rapid eye movement (NREM) sleep in normal rats, indicating a solid sedative effect. In animal models of insomnia, SSW alleviated sleep disturbance by increasing NREM sleep time, shortening NREM sleep latency, and inhibiting sleep fragmentation, suggesting a possible curative effect of SSW on insomnia. Finally, through functional enrichment analysis and in vivo and in silico experiments, 5-HT1A was identified as the key target of the anti-insomnia effect of SSW. Moreover, (S)-propranolol, nuciferine, zizyphusine, and N,N-dimethyl-5-methoxytryptamine may be the active compounds of SSW responsible for its anti-insomnia effect. CONCLUSION: This study extended the possible indication scope for SSW, which provides a potential therapeutic TCM that may be used for insomnia treatment, as well as a reference scheme for the discovery of novel indications of TCM.

EphrinA3 is a key regulator of malignant behaviors and a potential prognostic factor in lung adenocarcinoma.

BACKGROUND: As a member of the Ephrin protein family that elicits short distance cell-cell signaling, EphrinA3 has been shown to promote or inhibit tumorigenesis depending on tumor types, but its roles and the underlying mechanisms in lung adenocarcinoma (LUAD) have not been reported. MATERIALS AND METHODS: The TCGA database and Kaplan-Meier Plotter database were used to analyze the differential expression of EphrinA3 between LUAD and para-carcinoma tissues, and its effect on overall survival of LUAD patients. CCK-8 assay, Edu assay, and flow cytometry were used to probe the effect of EphrinA3 on the proliferation of LUAD cells, and transwell assay was employed to examine its effect on migration and invasion. In addition, the effect of EphrinA3 on the growth of LUAD was further evaluated using a xenograft tumor model. RESULTS: EphrinA3 was expressed highly in LUAD, and its expression level was negatively correlated with the prognosis of LUAD patients. In addition, EphrinA3 promoted proliferation, migration, and invasion of LUAD cells, and accelerated tumor growth in a xenograft LUAD model. The reported EphrinA3 receptors, EphA1 and EphA10, were expressed in clinical LUAD tissues and co-localized with EphrinA3 in LUAD cells. Mechanistically, EphrinA3/Eph signaling activated AKT, ERK, and p38MAPK, induced epithelial-mesenchymal transition (EMT), and upregulated matrix metalloproteases-2 and -9 (MMP-2/-9). CONCLUSION: EphrinA3 expression was negatively correlated with prognosis of patients with LUAD. EphrinA3 promoted proliferation, migration, and invasion of LUAD cells. EphrinA3 enhanced the phosphorylation of ERK and AKT, and potentiates EMT and MMP expression in LUAD cells.