Sequence pre-training-based graph neural network for predicting lncRNA-miRNA associations.

MicroRNAs (miRNAs) silence genes by binding to messenger RNAs, whereas long non-coding RNAs (lncRNAs) act as competitive endogenous RNAs (ceRNAs) that can relieve miRNA silencing effects and upregulate target gene expression. The ceRNA association between lncRNAs and miRNAs has been a research hotspot due to its medical importance, but it is challenging to verify experimentally. In this paper, we propose a novel deep learning scheme, i.e. sequence pre-training-based graph neural network (SPGNN), that combines pre-training and fine-tuning stages to predict lncRNA-miRNA associations from RNA sequences and the existing interactions represented as a graph. First, we utilize a sequence-to-vector technique to generate pre-trained embeddings based on the sequences of all RNAs during the pre-training stage. In the fine-tuning stage, we use Graph Neural Network to learn node representations from the heterogeneous graph constructed using lncRNA-miRNA association information. We evaluate our proposed scheme SPGNN on our newly collected animal lncRNA-miRNA association dataset and demonstrate that combining the $k$-mer technique and Doc2vec model for pre-training with the Simple Graph Convolution Network for fine-tuning is effective in predicting lncRNA-miRNA associations. Our approach outperforms state-of-the-art baselines across various evaluation metrics. We also conduct an ablation study and hyperparameter analysis to verify the effectiveness of each component and parameter of our scheme. The complete code and dataset are available on GitHub: https://github.com/zixwang/SPGNN.

Intermediate-state imaging of electrical switching and quantum coupling of molybdenum disulfide monolayer.

SignificanceThin transparent semiconductors of two-dimensional materials are attractive for the practical applications in next-generation nanoelectronic and optoelectronic devices. Probing the electron states and electrical switching mechanisms of a molybdenum disulphide monolayer with atomic-scale thickness (6.5 Å) allows us to unlock the full technological potential of this nanomaterial. We introduced a plasmonic phase imaging method to uncover the underlying mechanism and detailed switching dynamics of an electrical-state switching event. This dramatic phase change can be attributed to the reversible switching of classical electromagnetic coupling and quantum coupling effects interplaying between a single metal nanoparticle and molybdenum disulphide monolayer, and the transient intermediate states during the switching event can be directly imaged by a plasmonic technique.

Electrochemically controlled rectification in symmetric single-molecule junctions.

Single-molecule electrochemical science has advanced over the past decades and now extends well beyond molecular imaging, to molecular electronics functions such as rectification and amplification. Rectification is conceptually the simplest but has involved mostly challenging chemical synthesis of asymmetric molecular structures or asymmetric materials and geometry of the two enclosing electrodes. Here we propose an experimental and theoretical strategy for building and tuning in situ (in operando) rectification in two symmetric molecular structures in electrochemical environment. The molecules were designed to conduct electronically via either their lowest unoccupied molecular orbital (LUMO; electron transfer) or highest occupied molecular orbital (HOMO; "hole transfer"). We used a bipotentiostat to control separately the electrochemical potential of the tip and substrate electrodes of an electrochemical scanning tunneling microscope (EC-STM), which leads to independent energy alignment of the STM tip, the molecule, and the STM substrate. By creating an asymmetric energy alignment, we observed single-molecule rectification of each molecule within a voltage range of ±0.5 V. By varying both the dominating charge transporting LUMO or HOMO energy and the electrolyte concentration, we achieved tuning of the polarity as well as the amplitude of the rectification. We have extended an earlier proposed theory that predicts electrolyte-controlled rectification to rationalize all the observed in situ rectification features and found excellent agreement between theory and experiments. Our study thus offers a way toward building controllable single-molecule rectifying devices without involving asymmetric molecular structures.

Extraction of rare earth Eu from waste blue phosphor strengthened by microwave alkali roasting.

Spent phosphor is an important secondary resource for extracting rare earth elements. Microwave absorption properties and enhanced extraction of Eu from blue phosphor by microwave alkali roasting were studied. Dielectric properties of alkali roasting system were measured by resonator perturbation method. Dielectric constant increases linearly from 250 °C until it reaches a peak at 400 °C. The dielectric loss reaches a higher value at 400-550 °C, due to the strong microwave absorption properties of molten alkali and roasted products. Effects of roasting temperature, roasting time and alkali addition amount on Eu leaching were investigated. The phosphor was completely decomposed into Eu2O3, BaCO3 and MgO at 400 °C. The alkaline decomposition process of phosphor is more consistent with diffusion control model with Eα being 28.9 kJ/mol. Effects of the main leaching conditions on Eu leaching were investigated. The leaching kinetic of Eu was in line with diffusion control model with Eα being 5.74 kJ/mol. The leaching rules of rare earths in the mixed phosphor were studied. The results showed that the presence of red and green phosphor affected the recovery of blue phosphor. The optimum process parameters of rare earth recovery in single blue phosphor and mixed phosphor were obtained, and the recovery of Eu were 97.81% and 94.80%, respectively. Microwave alkali roasting promoted the dissociation of phosphor and leaching of rare earths. The results can provide reference for the efficient and selective recovery of rare earths in phosphors.

Taming Two-Dimensional Polymerization by a Machine-Learning Discovered Crystallization Model.

Rapidly synthesizing high-quality two-dimensional covalent organic frameworks (2D COFs) is crucial for their practical applications. While strategies such as slow monomer addition have been developed based on an empirical understanding of their formation process, quantitative guidance remains absent, which prohibits precise optimizations of the experimental conditions. Here, we use a machine-learning approach that overcomes the challenges associated with bottom-up model derivation for the non-classical 2D COF crystallization processes. The resulting model, referred to as NEgen1, establishes correlations among the induction time, nucleation rate, growth rate, bond-forming rate constants, and common solution synthesis conditions for 2D COFs that grow by a nucleation-elongation mechanism. The results elucidate the detailed competition between the nucleation and growth dynamics in solution, which has been inappropriately described previously by classical, empirical models with assumptions invalid for 2D COF polymerization. By understanding the dynamic processes at play, the NEgen1 model reveals a simple strategy of gradually increasing monomer addition speed for growing large 2D COF crystals. This insight enables us to rapidly synthesize large COF-5 colloids, which could only be achieved previously by prolonged reaction times or by introducing chemical modulators. These results highlight the potential for systematically improving the crystal quality of 2D COFs, which has wide-reaching relevance for many of the applications where 2D COFs are speculated to be valuable.

Efficient Silver(I)-Containing I-Motif DNA Hybrid Catalyst for Enantioselective Diels-Alder Reactions.

The inherent chiral structures of DNA serve as attractive scaffolds to construct DNA hybrid catalysts for valuable enantioselective transformations. Duplex and G-quadruplex DNA-based enantioselective catalysis has made great progress, yet novel design strategies of DNA hybrid catalysts are highly demanding and atomistic analysis of active centers is still challenging. DNA i-motif structures could be finely tuned by different cytosine-cytosine base pairs, providing a new platform to design DNA catalysts. Herein, we found that a human telomeric i-motif DNA containing cytosine-silver(I)-cytosine (C-Ag+-C) base pairs interacting with Cu(II) ions (i-motif DNA(Ag+)/Cu2+) could catalyze Diels-Alder reactions with full conversions and up to 95 % enantiomeric excess. As characterized by various physicochemical techniques, the presence of Ag+ is proved to replace the protons in hemiprotonated cytosine-cytosine (C : C+) base pairs and stabilize the DNA i-motif to allow the acceptance of Cu(II) ions. The i-motif DNA(Ag+)/Cu2+ catalyst shows about 8-fold rate acceleration compared with DNA and Cu2+. Based on DNA mutation experiments, thermodynamic studies and density function theory calculations, the catalytic center of Cu(II) ion is proposed to be located in a specific loop region via binding to one nitrogen-7 atom of an unpaired adenine and two phosphate-oxygen atoms from nearby deoxythymidine monophosphate and deoxyadenosine monophosphate, respectively.

Tuning Crystallinity and Stacking of Two-Dimensional Covalent Organic Frameworks through Side-Chain Interactions.

Two-dimensional covalent organic frameworks (2D COFs) form as layered 2D polymers whose sheets stack through high-surface-area, noncovalent interactions that can give rise to different interlayer arrangements. Manipulating the stacking of 2D COFs is crucial since it dictates the effective size and shape of the pores as well as the specific interactions between functional aromatic systems in adjacent layers, both of which will strongly influence the emergent properties of 2D COFs. However, principles for tuning layer stacking are not yet well understood, and many 2D COFs are disordered in the stacking direction. Here, we investigate effects of pendant chain length through a series of 2D imine-linked COFs functionalized with n-alkyloxy chains varying in length from one carbon (C1 COF) to 11 carbons (C11 COF). This series reveals previously unrecognized and unanticipated trends in both the stacking geometry and crystallinity. C1 COF adopts an averaged eclipsed geometry with no apparent offset between layers. In contrast, all subsequent chain lengths lead to some degree of unidirectional slip stacking. As pendant chain length is increased, trends show average layer offset increasing to a maximum of 2.07 Å in C5 COF and then decreasing as chain length is extended through C11 COF. Counterintuitively, shorter chains (C2-C4) give rise to lower yields of weakly crystalline materials, while longer chains (C6-C9) produce greater yields of highly crystalline materials, as confirmed by powder X-ray diffraction and scanning electron microscopy. Molecular dynamics simulations corroborate these observations, suggesting that long alkyl chains can interact favorably to promote the self-assembly of sheets. In situ proton NMR spectroscopy provides insights into the reaction equilibrium as well as the relationship between low COF yields and low crystallinity. These results provide fundamental insights into principles of supramolecular assembly in 2D COFs, demonstrating an opportunity for harnessing favorable side-chain interactions to produce highly crystalline materials.

Discovery of novel JAK1 inhibitors through combining machine learning, structure-based pharmacophore modeling and bio-evaluation.

BACKGROUND: Janus kinase 1 (JAK1) plays a critical role in most cytokine-mediated inflammatory, autoimmune responses and various cancers via the JAK/STAT signaling pathway. Inhibition of JAK1 is therefore an attractive therapeutic strategy for several diseases. Recently, high-performance machine learning techniques have been increasingly applied in virtual screening to develop new kinase inhibitors. Our study aimed to develop a novel layered virtual screening method based on machine learning (ML) and pharmacophore models to identify the potential JAK1 inhibitors. METHODS: Firstly, we constructed a high-quality dataset comprising 3834 JAK1 inhibitors and 12,230 decoys, followed by establishing a series of classification models based on a combination of three molecular descriptors and six ML algorithms. To further screen potential compounds, we constructed several pharmacophore models based on Hiphop and receptor-ligand algorithms. We then used molecular docking to filter the recognized compounds. Finally, the binding stability and enzyme inhibition activity of the identified compounds were assessed by molecular dynamics (MD) simulations and in vitro enzyme activity tests. RESULTS: The best performance ML model DNN-ECFP4 and two pharmacophore models Hiphop3 and 6TPF 08 were utilized to screen the ZINC database. A total of 13 potentially active compounds were screened and the MD results demonstrated that all of the above molecules could bind with JAK1 stably in dynamic conditions. Among the shortlisted compounds, the four purchasable compounds demonstrated significant kinase inhibition activity, with Z-10 being the most active (IC50 = 194.9 nM). CONCLUSION: The current study provides an efficient and accurate integrated model. The hit compounds were promising candidates for the further development of novel JAK1 inhibitors.

Single-channel system for joint unambiguous measurement of DFS and AOA based on serrodyne modulation.

In this paper, a photonic-assisted system for simultaneous and unambiguous measurement of the Doppler frequency shift (DFS) and angle-of-arrival (AOA) using a dual-parallel dual-drive Mach-Zehnder modulator (DP-DDMZM) is proposed and investigated. The echo signals received by two receiving antennas are applied to the radio frequency ports of one sub-DDMZM of the DP-DDMZM. The bias port of the sub-DDMZM is fed by a binary electrical signal that is used to construct two different mapping curves on the relationship between the phase difference and the power of the output intermediate frequency (IF) signal. Therefore, unambiguous AOA measurement with extended range can be realized. The transmitted signal is input into the other sub-DDMZM to implement single-sideband modulation, which is then frequency shifted based on serrodyne modulation. Both the value and direction of DFS can be derived intuitively from the frequency of the output IF signal. Simulation results show that the measurement error of unambiguous DFS measurement is no more than ±0.008H z in the range of -100k H z to 100 kHz, and the measurement error of unambiguous AOA is less than ±0.2∘ in the range of -70.8∘ to 70.8°. Moreover, since the scheme does not involve the construction of multi-channels or use of any filter or polarization dependent device, the system has concise structure, high accuracy, large operating bandwidth, and strong robustness, and can be considered as a very promising solution for actual applications.

Directly Imaging and Regulating the Nanoscale Inhomogeneity of S-Vacancies in Molybdenum Disulfide Monolayer during Electrocatalytic Hydrogen Evolution.

The study of electron transfer event on two-dimensional (2D) layered transition metal dichalcogenides has attracted tremendous attentions attributing to their promising applications in electrochemical devices. Herein, we demonstrate an opto-electrochemical strategy to directly map and regulate electron transfer event on molybdenum disulfide (MoS2 ) monolayer by combining bright field (BF) imaging technique with electrochemical modulation. The heterogeneity of electrochemical activity on MoS2 monolayer down to nanoscale is resolved spatiotemporally. The thermodynamics of MoS2 monolayer is measured during electrocatalytic hydrogen evolution, and the Arrhenius correlations are obtained. We validate that the defect generation engineered by oxygen plasma bombardment dramatically enhances the local electrochemical activity of MoS2 monolayer, which can be attributed to point defects of S-vacancies as evidenced. Furthermore, by comparing the difference of electron transfer event on MoS2 with various layers, the interlayer coupling effect is uncovered. This study represents a facile method to image the heterogeneity of electrochemical properties for nanomaterials with atomic thickness and regulate the local activity within the plane by extrinsic factors. It also has potential applications in the design and evaluation of high-performance layered electrochemical systems down to nanoscale.

Radical chemistry in polymer science: an overview and recent advances.

Radical chemistry is one of the most important methods used in modern polymer science and industry. Over the past century, new knowledge on radical chemistry has both promoted and been generated from the emergence of polymer synthesis and modification techniques. In this review, we discuss radical chemistry in polymer science from four interconnected aspects. We begin with radical polymerization, the most employed technique for industrial production of polymeric materials, and other polymer synthesis involving a radical process. Post-polymerization modification, including polymer crosslinking and polymer surface modification, is the key process that introduces functionality and practicality to polymeric materials. Radical depolymerization, an efficient approach to destroy polymers, finds applications in two distinct fields, semiconductor industry and environmental protection. Polymer chemistry has largely diverged from organic chemistry with the fine division of modern science but polymer chemists constantly acquire new inspirations from organic chemists. Dialogues on radical chemistry between the two communities will deepen the understanding of the two fields and benefit the humanity.

Design, synthesis and biological evaluation of novel pyrazinone derivatives as PI3K/HDAC dual inhibitors.

PI3Ks and HDACs play essential roles in the occurrence and progression of leukemia. Herein, a series of novel pyrazin-2(1H)-one derivatives were rationally designed and synthesized as novel dual PI3K and HDAC inhibitors based on scaffold replacement and heterozygous strategies. Most of the target compounds showed potent inhibitory potency to PI3Kα and HDAC6. Especially, compound 9q displayed PI3Kα and HDAC6 inhibitory with IC50 values of 372 nM and 4.5 nM, and anti-proliferative activity against MV4-11 cells with IC50 value of 0.093 ± 0.012 µM. Further mechanistic studies revealed that 9q induced apoptosis, arrested the cell cycle in the G2/M phase, promoted the acetylation of α-tubulin, and blocked the PI3K/AKT/mTOR signal way in MV4-11 cells. All the results demonstrated that 9q was a promising lead candidate for further development of novel PI3K/HDAC dual inhibitors for leukemia treatment.

Thyroid Feedback Quantile-Based Index Is Associated With Blood Pressure and Other Hemodynamic Measures: A Cross-sectional Study.

OBJECTIVE: Previous studies have reported inconsistent relationships between thyroid function and blood pressure (BP) levels. We aimed to explore the associations between thyroid hormone sensitivity and BP parameters. METHODS: This retrospective study included 6272 participants who underwent a health examination at the First Hospital of China Medical University between January 2017 and December 2018. The Thyroid Feedback Quantile-based Index (TFQI), Parametric TFQI, thyroid-stimulating hormone index, and thyrotroph thyroxine resistance index were calculated to reflect thyroid hormone sensitivity. Mean arterial pressure, pulse pressure, and rate-pressure product were used to indirectly represent arterial stiffness. RESULTS: The TFQI was positively associated with systolic BP (ß = 3.22), diastolic BP (ß =2.32), and mean arterial pressure (ß = 2.62) (P < .001, for all). Analyses of the Parametric TFQI, thyroid-stimulating hormone index, and thyrotroph thyroxine resistance index yielded similar results. The TFQI was positively related to pulse pressure and rate-pressure product. With a 1 SD increase in the TFQI, the adjusted odds ratio for hypertension was 1.11 (95% CI 1.04-1.18). When comparing the fourth quartile of the TFQI with the first, the odds ratio for hypertension was 1.27 (95% CI 1.07-1.51, Pfor trend = .006). These relationships remained significant when stratified by age, sex, and body mass index. Similar results were observed in a euthyroid or normotensive population. CONCLUSION: The TFQI was positively associated with BP and markers of arterial stiffness. Impaired thyroid hormone sensitivity was related to increased risk for hypertension.

Transition from stochastic events to deterministic ensemble average in electron transfer reactions revealed by single-molecule conductance measurement.

Electron transfer reactions can now be followed at the single-molecule level, but the connection between the microscopic and macroscopic data remains to be understood. By monitoring the conductance of a single molecule, we show that the individual electron transfer reaction events are stochastic and manifested as large conductance fluctuations. The fluctuation probability follows first-order kinetics with potential dependent rate constants described by the Butler-Volmer relation. Ensemble averaging of many individual reaction events leads to a deterministic dependence of the conductance on the external electrochemical potential that follows the Nernst equation. This study discloses a systematic transition from stochastic kinetics of individual reaction events to deterministic thermodynamics of ensemble averages and provides insights into electron transfer processes of small systems, consisting of a single molecule or a small number of molecules.

A retrospective and prospective study to establish a preoperative difficulty predicting model for video-assisted thoracoscopic lobectomy and mediastinal lymph node dissection.

BACKGROUND: In previous studies, the difficulty of surgery has rarely been used as a research object. Our study aimed to develop a predictive model to enable preoperative prediction of the technical difficulty of video-assisted thoracoscopic lobectomy and mediastinal lymph node dissection using retrospective data and to validate our findings prospectively. METHODS: Collected data according to the designed data table and took the operation time as the outcome variable. A nomogram to predict the difficulty of surgery was established through Lasso logistic regression. The prospective datasets were analyzed and the outcome was the operation time. RESULTS: This retrospective study enrolled 351 patients and 85 patients were included in the prospective datasets. The variables in the retrospective research were selected by Lasso logistic regression (only used for modeling and not screening), and four significantly related influencing factors were obtained: FEV1/FVC (forced expiratory volume in the first second/forced vital capacity) (p < 0.001, OR, odds ratio = 0.89, 95% CI, confidence interval = 0.84-0.94), FEV1/pred FEV1 (forced expiratory volume in the first second/forced expiratory volume in the first second in predicted) (p = 0.076, OR = 0.98, 95% CI = 0.95-1.00), history of lung disease (p = 0.027, OR = 4.00, 95% CI = 1.27-15.64), and mediastinal lymph node enlargement or calcification (p < 0.001, OR = 9.78, 95% CI = 5.10-19.69). We used ROC (receiver operating characteristic) curves to evaluate the model. The training set AUC (area under curve) value was 0.877, the test set's AUC was 0.789, and the model had a good calibration curve. In a prospective study, the data obtained in the research cohort were brought into the model again for verification, and the AUC value was 0.772. CONCLUSION: Our retrospective study identified four preoperative variables that are correlated with a longer surgical time and can be presumed to reflect more difficult surgical procedures. Our prospective study verified that the variables in the prediction model (including prior lung disease, FEV1/pred FEV1, FEV1/FVC, mediastinal lymph node enlargement or calcification) were related to the difficulty.

Author Correction: Gate controlling of quantum interference and direct observation of anti-resonances in single molecule charge transport.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Timing of force application on buccal tooth movement into bone-grafted alveolar defects: A pilot study in dogs.

INTRODUCTION: The aim of this pilot study was to evaluate the effect of the timing of postoperative orthodontic force application on bone remodeling during tooth movement into surgical alveolar defects with bone grafts in beagle dogs. METHODS: Six beagle dogs underwent surgery for buccal dehiscence-type defects (width, 5 mm; height, 6 mm) on the distal root of maxillary second premolars bilaterally for 12 defects. After 1-month healing, bone-augmentation procedures were undertaken at the dehiscence defects. The second premolars were protracted buccally for 6 weeks into the surgical sites immediately (F-0), at 4 weeks (F-4), or 8 weeks (F-8) after grafting. Orthodontic tooth movement was monitored using digital models. Remodeling of alveolar bone was evaluated by histology, histomorphometry, immunohistochemistry, microcomputed tomography, and fluorescence microscopy. RESULTS: Group F-0 showed significant expansion (mean, 2.42 mm) and tipping (mean, 9.03°) after completing orthodontic tooth treatment. The vertical bone defect was significantly lower in groups F-4 and F-8 than that in group F-0 (mean, 2.1, 2.7, and 4.5 mm, respectively). In group F-4, the formation of new bone and mineralization were significantly greater than those in groups F-0 and F-8 (P <0.05). Group F-4 showed a minimal amount of bone-material remnants. Immunohistochemistry showed the highest expression of collagen-1 and osteopontin in group F-4, followed by group F-8 and group F-0, which demonstrated high osteoblast activity and enhanced bone remodeling in group F-4. CONCLUSIONS: Orthodontic force application at 4 weeks after an augmentation procedure provided the best functional stimulation for an alveolar bone graft. This strategy enhanced new-bone regeneration and degradation of bone substitutes and, eventually, promoted bone remodeling in the bone-grafted area.

Gate controlling of quantum interference and direct observation of anti-resonances in single molecule charge transport.

Quantum interference can profoundly affect charge transport in single molecules, but experiments can usually measure only the conductance at the Fermi energy. Because, in general, the most pronounced features of the quantum interference are not located at the Fermi energy, it is highly desirable to probe charge transport in a broader energy range. Here, by means of electrochemical gating, we measure the conductance and map the transmission functions of single molecules at and around the Fermi energy, and study signatures associated with constructive and destructive interference. With electrochemical gate control, we tune the quantum interference between the highest occupied molecular orbital and lowest unoccupied molecular orbital, and directly observe anti-resonance, a distinct feature of destructive interference. By tuning the molecule in and out of anti-resonance, we achieve continuous control of the conductance over two orders of magnitude with a subthreshold swing of ~17 mV dec-1, features relevant to high-speed and low-power electronics.

Sensitive and selective monitoring of the DNA damage-induced intracellular p21 protein and unraveling the role of the p21 protein in DNA repair and cell apoptosis by surface plasmon resonance.

The cyclin-dependent kinase inhibitor p21 protein is a critical regulator that mediates various biological activities, such as cell cycle progression, apoptosis, and cellular senescence. As a DNA damage-inducing agent, doxorubicin could reactivate the transcriptional activity of p53 and modulate the p21 protein level. In this work, sensitive and selective monitoring of the intracellular p21 protein in doxorubicin-treated breast cancer cells was conducted using surface plasmon resonance (SPR). The fluidic channels were pre-immobilized with double stranded (ds) DNA/proliferating cell nuclear antigen (PCNA) for the capture of the p21 protein. The incorporation of the anti-p21 antibody-streptavidin conjugate pre-formed between streptavidin and biotinylated anti-p21 antibody that specifically recognizes the p21 protein leads to signal amplification. The detection limit of 0.85 pM for the p21 protein was lower than that using the commercial enzyme-linked immunosorbent assay (ELISA) kit. The treatment of MCF-7 breast cancer cells with wild-type p53 by various doses of doxorubicin leads to differences in the extent of DNA damage. Low-level DNA damage by low-dose doxorubicin up-regulates the p21 level, and p21 exerts its anti-apoptotic function, causing p53-dependent cell cycle arrest and DNA repair. However, massive DNA damage by high-dose doxorubicin represses the expression of the p21 protein through increased proteasome activity, leading to cell apoptosis. The proposed method is sensitive, selective and label-free, holding great promise for the assay of the DNA damage-induced intracellular p21 protein and understanding of p21 protein-mediated cell cycle arrest, DNA repair, and cell apoptosis.

Discovery of novel 2,4-disubstituted pyrimidines as Aurora kinase inhibitors.

In order to explore novel Aurora kinase inhibitors, a series of novel 2,4-disubstituted pyrimidines were designed, synthesized and evaluated their in vitro anti-proliferative activities against a panel of cancerous cell lines (A549, HCT-116 and MCF-7). Among them, compound 12a showed the moderate to high anti-proliferative activities against A549 (IC50 = 12.05 ± 0.45 µM), HCT-116 (IC50 = 1.31 ± 0.41 µM) and MCF-7 (IC50 = 20.53 ± 6.13 µM) cells, as well as the Aurora A and Aurora B inhibitory activities with the IC50 values of 309 nM and 293 nM, respectively. Furthermore, compound 12a induced apoptosis by upregulated the pro-apoptotic proteins Bax and decreased the anti-apoptotic protein Bcl-xl in HCT-116 cells. Moreover, the molecular docking study showed that compound 12a had good binding modes with Aurora A and Aurora B and the bioinformatics prediction discovered that compound 12a exhibited good drug likeness using SwissADME. Taken together, these results indicated that 12a may be a potential anticancer compound that was worthy of further development as Aurora kinase inhibitor.