Surfactant Micelle-Driven High-Efficiency and High-Resolution Length Separation of Carbon Nanotubes for Electronic Applications.

High-efficiency extraction of long single-wall carbon nanotubes (SWCNTs) with excellent optoelectronic properties from SWCNT solution is critical for enabling their application in high-performance optoelectronic devices. Here, a straightforward and high-efficiency method is reported for length separation of SWCNTs by modulating the concentrations of binary surfactants. The results demonstrate that long SWCNTs can spontaneously precipitate for binary-surfactant but not for single-surfactant systems. This effect is attributed to the formation of compound micelles by binary surfactants that squeeze the free space of long SWCNTs due to their large excluded volumes. With this technique, it can readily separate near-pure long (≥500 nm in length, 99% in content) and short (≤500 nm in length, 98% in content) SWCNTs with separation efficiencies of 26% and 64%, respectively, exhibiting markedly greater length resolution and separation efficiency than those of previously reported methods. Thin-film transistors fabricated from extracted semiconducting SWCNTs with lengths >500 nm exhibit significantly improved electrical properties, including a 10.5-fold on-state current and 14.7-fold mobility, compared with those with lengths <500 nm. The present length separation technique is perfectly compatible with various surfactant-based methods for structure separations of SWCNTs and is significant for fabrication of high-performance electronic and optoelectronic devices.

Effect of NO2 on N2 O production and NOx emission reduction in NH3 Selective Catalytic Reduction.

With the introduction of increasingly strict emission regulations, reducing nitrogen oxide (NOx ) emissions and nitrous oxide (N2 O) production from diesel engines have become the focus of research. At high temperature, the reaction of NO2 in the catalyst generates the intermediate product NH4 NO3 , which first crystallizes below 300 °C. These crystals tend to block the pores and inhibit the reaction. Subsequently, N2 O is produced through the decomposition of NH4 NO3 , leading to additional pollution. Therefore, the concentration of NO2 has a direct impact on both the NOx conversion efficiency and the generation of N2 O, requiring consideration of the optimal proportion of NO2 in SCR. Considering these two factors, it is concluded that the optimal amount of NO2 varies with temperature. To improve the NOx conversion rate of the Cu-SSZ-13 catalyst at low temperatures and reduce N2 O generation, the optimal NO2 ratio of the Cu-SSZ-13 catalyst under various operating conditions is studied using numerical simulations. As the temperature rises, the optimal NO2 /NOx ratio first increases and then decreases. Under the optimal NO2 /NOx ratio, the NOx conversion rate significantly increases, while N2 O generation decreases considerably. The optimal NO2 /NOx ratio also provides suggestions for the optimization of the DOC-DPF-DCR system.

A Light Multi-View Stereo Method with Patch-Uncertainty Awareness.

Multi-view stereo methods utilize image sequences from different views to generate a 3D point cloud model of the scene. However, existing approaches often overlook coarse-stage features, impacting the final reconstruction accuracy. Moreover, using a fixed range for all the pixels during inverse depth sampling can adversely affect depth estimation. To address these challenges, we present a novel learning-based multi-view stereo method incorporating attention mechanisms and an adaptive depth sampling strategy. Firstly, we propose a lightweight, coarse-feature-enhanced feature pyramid network in the feature extraction stage, augmented by a coarse-feature-enhanced module. This module integrates features with channel and spatial attention, enriching the contextual features that are crucial for the initial depth estimation. Secondly, we introduce a novel patch-uncertainty-based depth sampling strategy for depth refinement, dynamically configuring depth sampling ranges within the GRU-based optimization process. Furthermore, we incorporate an edge detection operator to extract edge features from the reference image's feature map. These edge features are additionally integrated into the iterative cost volume construction, enhancing the reconstruction accuracy. Lastly, our method is rigorously evaluated on the DTU and Tanks and Temples benchmark datasets, revealing its low GPU memory consumption and competitive reconstruction quality compared to other learning-based MVS methods.

High-sensitivity vector bend sensor based on a fiber directional coupler inscribed by a femtosecond laser.

In this Letter, we demonstrate a high-sensitivity vector bend sensor based on a fiber directional coupler. The fiber directional coupler is composed of two parallel waveguides inscribed within a no-core fiber (NCF) by a femtosecond laser. Since the two written waveguides have closely matched refractive indices and geometries, the transmission spectrum of the fiber directional coupler possesses periodic resonant dips. Such a fiber directional coupler exhibits a good bending-dependent spectral shift response due to its asymmetric structure. Experimental results show that bending sensitivities of -97.11 nm/m-1 and 58.22 nm/m-1 are achieved for the 0° and 180° orientations in the curvature range of 0-0.62 m-1, respectively. In addition, the proposed fiber directional coupler is shown to be insensitive to external humidity changes, thus improving its suitability in high-accuracy bending measurements.

Qualitative and Quantitative Assessment of Invasive Surgery Skill Based on a Custom Training Simulator.

PURPOSE: Qualitative and quantitative assessment of interventional performance is a vital component in the evaluation of endovascular surgery skill training. We established a custom simulator with qualitative and quantitative metrics for endovascular performance training. METHODS: The simulator included an in vitro silicone phantom, mock circulation loop, visual module, force-sensing module, and custom software for image and force data postprocessing. Two tasks to deliver the guidewire to the target location of the carotid artery were conducted by the expert (n=4), novice (n=6), and test (n=4) groups. Seven features with significant differences extracted from the expert and novice groups were applied for qualitative assessment using the support vector machine (SVM) and quantitative assessment using the Mahalanobis distance (MD). RESULTS: Significant differences were observed in kinematic and force data between experts and novices during the intervention procedure. The median value of finished time for task 1 was 26.88 seconds for experts and 63.36 seconds for novices. The maximum speed for experts and novices was 32.79 and 7.43 cm/s, respectively. Moreover, the classified results depicted that the accuracy of qualitative assessment for task 1 and task 2 was 96.67% and 90%, respectively. As for the quantitative data, the residents had higher scores than individuals majored in biomedical engineering at 2 tasks (70.06±5.30 vs 41.81±6.58 for task 1, p=0.001). CONCLUSIONS: The proposed endovascular intervention skill training simulator provides qualitative and quantitative metrics on intervention performance skills and may be a useful tool in future interventional surgical training. CLINICAL IMPACT: This simulator comprised an in-vitro silicone phantom, mock circulation loop, visual module, force-sensing module, and custom software for image and force data post-processing. Seven interventional performance features were used for qualitative assessment using the support vector machine and quantitative assessment using the Mahalanobis Distance. From the observations, we conclude that this endovascular intervention skill training simulator provides qualitative and quantitative metrics on intervention performance and may be a useful tool in future surgical training.

Ultrathin Layered Hyperbolic Metamaterial-Assisted Illumination Nanoscopy.

Metamaterial-assisted illumination nanoscopy (MAIN) has been proven to be a promising approach for super-resolution microscopy with up to a 7-fold improvement in imaging resolution. Further resolution enhancement is possible in principle, however, has not yet been demonstrated due to the lack of high-quality ultrathin layered hyperbolic metamaterials (HMMs) used in the MAIN. Here, we fabricate a low-loss composite HMM consisting of high-quality bilayers of Al-doped Ag and MgO with a nominal thickness of 2.5 nm, and then use it to demonstrate an ultrathin layered hyperbolic metamaterial-assisted illumination nanoscopy (ULH-MAIN) with a 14-fold imaging resolution improvement. This improvement of resolution is achieved in fluorescent beads super-resolution experiments and verified with scanning electron microscopy. The ULH-MAIN presents a simple super-resolution imaging approach that offers distinct benefits such as low illumination power, low cost, and a broad spectrum of selectable probes, making it ideal for dynamic imaging of life science samples.

Effect of soluble salts in electrolytic manganese residue on its geotechnical characteristics.

Electrolytic Manganese Residue (EMR) is a solid waste containing soluble sulfate, discharged by electrolytic manganese industries. The accumulation of EMR in ponds poses a significant hazard to both safety and the environment. This study utilized innovative geotechnical test techniques to conduct a series of tests, investigating the effect of soluble salts on the geotechnical characteristics of EMR. The results revealed that soluble sulfates had a significant impact on the geotechnical characteristics of the EMR. In particular, the infiltration of water leached away the soluble salts, causing a non-uniform particle size distribution and decreasing the shear strength, stiffness, and liquefaction resistance of the EMR. Nevertheless, an increase in the stacking density of EMR could improve its mechanical characteristics and inhibited the dissolution of soluble salts. Therefore, increasing the density of stacked EMR, ensuring the effectiveness and non-obstruction of the water interception facilities, and reducing rainwater infiltration could be effective measures to enhance the safety and reduce the environmental hazard of EMR ponds.

Two Antimicrobial Peptides Derived from Bacillus and Their Properties.

Growth promotion and disease prevention are important strategies in the modern husbandry industry, and for this reason, antibiotics are widely used as animal feed additives. However, the overuse of antibiotics has led to the serious problem of increasing resistance of pathogenic microorganisms, posing a major threat to the environment and human health. "Limiting antibiotics" and "Banning antibiotics" have become the inevitable trends in the development of the livestock feed industry, so the search for alternative antimicrobial agents has become a top priority. Antimicrobial peptides (AMPs) produced by Bacillus spp. have emerged as a promising alternative to antibiotics, due to their broad-spectrum antimicrobial activity against resistant pathogens. In this study, two strains of Bacillus velezensis 9-1 and B. inaquosorum 76-1 with good antibacterial activity were isolated from commercial feed additives, and the antimicrobial peptides produced by them were purified by ammonium sulfate precipitation, anion exchange chromatography, gel chromatography, and RP-HPLC. Finally, two small molecule peptides, named peptide-I and peptide-II, were obtained from strain 9-1 and 76-1, respectively. The molecular weight and sequences of the peptides were analyzed and identified by LC-MS/MS, which were 988.5706 Da and VFLENVLR, and 1286.6255 Da and FSGSGSGTAFTLR, respectively. The results of an antibacterial activity and stability study showed that the two peptides had good antibacterial activity against Staphylococcus aureus, B. cereus, and Salmonella enterica, and the minimum inhibitory concentrations were 64 µg/mL and 16 µg/mL, 32 µg/mL and 64 µg/mL, and 8 µg/mL and 8 µg/mL, respectively. All of them have good heat, acid, and alkali resistance and protease stability, and can be further developed as feed antibiotic substitutes.

Optofluidic tunable broadband distributed Bragg reflector based on liquid crystal polymer composites.

A dynamically reconfigurable liquid crystal (LC) photonic device is an important research field in modern LC photonics. We present a type of continuously tunable distributed Bragg reflector (DBR) based on LC polymer composites modulated via a novel optofluidic method. LC-templated DBR films are fabricated by photopolymerization under visible standing wave interference. The influences of the incident angle, incident light intensity, and content of ethanol as a pore-forming additive on the reflection behavior are discussed in detail. Then, the LC-templated DBR films are integrated into microfluidic channels and reversibly refilled by different organic solvents. The reconfigurable characteristics of optofluidic DBRs were demonstrated by changing the average refractive index (RI) of the mixed liquids and adjusting the flow rates, resulting in the dynamic and continuous variation of the reflection band within a specific visible light band. It is anticipated that the prototype optofluidic LC device will hopefully be applied to some specific scenarios where conventional means of regulation, such as electric, optical, and temperature fields, are unsuitable and possibly boost the development of microfluidic analysis techniques based on structural color.

Late preterm antenatal corticosteroids in singleton and twin gestations: a retrospective cohort study.

BACKGROUND: In 2016, the American College of Obstetricians and Gynecologists recommended antenatal corticosteroids in the late preterm period for women at risk for preterm delivery. Limited real-world evidence exists on neonatal outcomes, particularly for twin gestations, following the guideline change. The study objective is to determine the association of antenatal corticosteroids in late preterm singleton and twin pregnancies with respiratory complications and hypoglycemia in a real-world clinical setting. METHODS: This is a retrospective cohort study comprising late preterm deliveries (4,341 mother-child pairs) within the Mount Sinai Health System, 2012-2018. The exposure of interest is antenatal corticosteroid administration of betamethasone during pregnancy between 34 0/7 and 36 6/7 weeks. Our primary outcomes are neonatal respiratory complications and hypoglycemia. Multivariable logistic regression was used to estimate the association between antenatal corticosteroid exposure and these two outcomes. We stratified the study population by singleton gestations and twins to minimize the potential confounding from different obstetric management between the two groups. RESULTS: Among a total of 4,341 mother-child pairs (3,309 singleton and 1,032 twin mother-child pairs), 745 mothers received betamethasone, of which 40.94% (305/745) received the full course. Relative to no treatment, a full course of betamethasone was associated with reduced odds of respiratory complications (OR = 0.53, 95% CI:[0.31-0.85], p < 0.01) and increased odds of hypoglycemia (OR = 1.86, 95%CI:[1.34-2.56], p < 0.01) in singletons; however, the association with respiratory complications was not significant in twins (OR = 0.42, 95% CI:[0.11-1.23], p = 0.16), but was associated with increased odds of hypoglycemia (OR = 2.18, 95% CI:[1.12-4.10], p = 0.02). A partial course of betamethasone (relative to no treatment) was not significantly associated with any of the outcomes, other than respiratory complications in twins (OR = 0.34, 95% CI:[0.12-0.82], p = 0.02). CONCLUSIONS: Exposure to antenatal corticosteroids in singletons and twins is associated with increased odds of hypoglycemia. Among singletons, exposure to the full dosage (i.e. two doses) was associated with decreased odds of respiratory complications but this was only the case for partial dose among twins. Twin gestations were not studied by the Antenatal Late Preterm Steroids trial. Therefore, our study findings will contribute to the paucity of evidence on the benefit of antenatal corticosteroids in this group. Health systems should systematically monitor guideline implementations to improve patient outcomes.

High expression of oncogene cadherin-6 correlates with tumor progression and a poor prognosis in gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common and fatal cancers worldwide. Effective biomarkers to aid the early diagnosis of GC, as well as predict the course of disease, are urgently needed. Hence, we explored the role and function of cadherin-6 (CDH6) in the diagnosis and prognosis of gastric cancer. METHODS: The expression levels of CDH6 in cancerous and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset. The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and CDH6 expression were evaluated statistically, and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. 44 GC tissue samples, 20 donor-matched adjacent normal tissue samples, and associated detailed clinical information, were collected from the Tianjin Medical University General Hospital. CDH6 expression levels were determined for further validation. RESULTS: CDH6 was upregulated in GC samples compared to normal gastric tissue. Furthermore, GSEA identified the tricarboxylic acid (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism, oxidative phosphorylation, and the pentose phosphate pathway as differentially enriched in GC tissue samples. According to the area under the ROC curve (AUC) values (AUC = 0.829 in the TCGA and 0.966 in the GSE54129 dataset), CDH6 expression was associated with high diagnostic efficacy. Patients with high CDH6 levels in their GC tissues had a higher T number (according to the TNM classification) and a worse prognosis than those with low CDH6 expression. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001). CONCLUSION: CDH6 was upregulated in GC, and high CDH6 expression was indicative of a higher T number and a worse prognosis. Therefore, CDH6 represents a potentially independent molecular biomarker for the diagnostic and prognostic prediction of GC.

Construction and Validation of a Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Gastric Cancer.

BACKGROUND: Increasing evidence indicated that the tumor microenvironment (TME) plays a critical role in tumor progression. This study aimed to identify and evaluate mRNA signature involved in lymph node metastasis (LNM) in TME for gastric cancer (GC). METHODS: Gene expression and clinical data were downloaded from The Cancer Genome Atlas (TCGA). The ESTIMATE algorithm was used to evaluate the TME of GC. The heatmap and Venn plots were applied for visualizing and screening out intersect differentially expressed genes (DEGs) involved in LNM in TME. Functional enrichment analysis, gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network were also conducted. Furthermore, binary logistic regression analysis were employed to develop a 4-mRNAs signature for the LNM prediction. ROC curves were applied to validate the LNM predictive ability of the riskscore. Nomogram was constructed and calibration curve was plotted to verify the predictive power of nomogram. RESULTS: A total of 88 LNM related DEGs were identified. Functional enrichment analysis and GSEA implied that those genes were associated with some biological processes, such as ion transportation, lipid metabolism and thiolester hydrolase activity. After univariate and multivariate logistic regression analysis, 4 mRNAs (RASSF2, MS4A2, ANKRD33B and ADH1B) were eventually screened out to develop a predictive model. ROC curves manifested the good performance of the 4-mRNAs signature. The proportion of patients with LNM in high-risk group was significantly higher than that in low-risk group. The C-index of nomogram from training and test cohorts were 0.865 and 0.765, and the nomogram was well calibrated. CONCLUSIONS: In general, we identified a 4-mRNAs signature that effectively predicted LNM in GC patients. Moreover, the 4-mRNAs signature and nomogram provide a guidance for the preoperative evaluation and postoperative treatment of GC patients.

Photoluminescence Quantum Yield of Single-Wall Carbon Nanotubes Corrected for the Photon Reabsorption Effect.

Photoluminescence (PL) from single-wall carbon nanotubes (SWCNTs) enables structural identification, but to derive the content rate of the specific chirality species it is necessary to know the quantum yield of each chirality. However, in the PL of SWCNTs, because the Stokes shift is small, the photon reabsorption effect is dominant and the apparent PL spectral shape and emission intensity are greatly modified depending on the concentration. This problem makes quantitative identification of SWCNTs by PL difficult. In this study, the concentration dependence of the PL of SWCNTs separated into a few chiralities was analyzed in detail, including the effect of reabsorption. It is clear that all changes in the PL spectrum occurring in the high concentration range can be explained simply by the reabsorption effect, and additional effects such as Coulomb interactions between SWCNTs can be negligible. Furthermore, a reliable quantum yield was derived from the emission intensity corrected for the reabsorption effect. The PL quantum yield varied with SWCNT chirality and exhibited a clear "family pattern". This is consistent with the theoretical report showing that the chirality-dependent PL quantum yield is dominated mainly by relaxation by optical phonons from E22 to E11.

Metamaterial-Assisted Photobleaching Microscopy with Nanometer Scale Axial Resolution.

The past two decades have witnessed a dramatic progress in the development of novel super-resolution fluorescence microscopy technologies. Here, we report a new fluorescence imaging method, called metamaterial-assisted photobleaching microscopy (MAPM), which possesses a nanometer-scale axial resolution and is suitable for broadband operation across the entire visible spectrum. The photobleaching kinetics of fluorophores can be greatly modified via a separation-dependent energy transfer process to a nearby metamaterial. The corresponding photobleaching rate is thus linked to the distance between the fluorophores and the metamaterial layer, leading to a reconstructed image with exceptionally high axial resolution. We apply the MAPM technology to image the HeLa cell membranes tagged with fluorescent proteins and demonstrate an axial resolution of ∼2.4 nm with multiple colors. MAPM utilizes a metamaterial-coated substrate to achieve super-resolution without altering anything else in a conventional microscope, representing a simple solution for fluorescence imaging at nanometer axial resolution.

Synthesis and biological evaluation of novel (E)-N'-benzylidene hydrazides as novel c-Met inhibitors through fragment based virtual screening.

C-Met plays a crucial role in the development and progression of neoplastic disease. Type II c-Met inhibitors recognise the inactive DFG-out conformation of the kinase, result in better anti-tumour effects due to synergistic effect against the other kinases. According to our previous works, an (E)-N'-benzylidene group was selected as the initial fragment. Two series of (E)-N'-benzylidene hydrazides were designed by fragment growth method. The inhibitory activities were in vitro investigated against c-Met and VEGFR-2. Compound 10b exhibited the most potent inhibitory activity against the c-Met inhibitor (IC50 = 0.37 nM). Compound 11b exhibited multi-target c-Met kinase inhibitory activity as a potential type II c-Met inhibitor (IC50 = 3.41 nM against c-Met; 25.34 nM against VEGFR-2). The two compounds also demonstrate the feasibility of fragment-based virtual screening method for drug discovery.

Identification of novel CDK2 inhibitors by a multistage virtual screening method based on SVM, pharmacophore and docking model.

Cyclin-dependent kinase 2 (CDK2) is the family of Ser/Thr protein kinases that has emerged as a highly selective with low toxic cancer therapy target. A multistage virtual screening method combined by SVM, protein-ligand interaction fingerprints (PLIF) pharmacophore and docking was utilised for screening the CDK2 inhibitors. The evaluation of the validation set indicated that this method can be used to screen large chemical databases because it has a high hit-rate and enrichment factor (80.1% and 332.83 respectively). Six compounds were screened out from NCI, Enamine and Pubchem database. After molecular dynamics and binding free energy calculation, two compounds had great potential as novel CDK2 inhibitors and they also showed selective inhibition against CDK2 in the kinase activity assay.

On-Chip Rolling Design for Controllable Strain Engineering and Enhanced Photon-Phonon Interaction in Graphene.

On-chip strain engineering is highly demanded in 2D materials as an effective route for tuning their extraordinary properties and integrating consistent functionalities toward various applications. Herein, rolling technique is proposed for strain engineering in monolayer graphene grown on a germanium substrate, where compressive or tensile strain could be acquired, depending on the designed layer stressors. Unusual compressive strains up to 0.30% are achieved in the rolled-up graphene tubular structures. The subsequent phonon hardening under compressive loading is observed through strain-induced Raman G band splitting, while distinct blueshifts of characteristic peaks (G+ , G- , or 2D) can be well regulated on an asymmetric tubular structure with a strain variation. In addition, due to the strong confinement of the local electromagnetic field under 3D tubular geometry, the photon-phonon interaction is highly strengthened, and thus, the Raman scattering of graphene in rolled-up tubes is enhanced. Such an on-chip rolling approach leads to a superior strain tuning method in 2D materials and could improve their light-matter interaction in a tubular configuration, which may hold great capability in 2D materials integration for on-chip applications such as in mechanics, electronics, and photonics.

Selected and Enhanced Single Whispering-Gallery Mode Emission from a Mesostructured Nanomembrane Microcavity.

Quantum sciences are revolutionizing computing and communication technologies, in which single-photon emitters are the key components for creating strong quantum entanglement. Color centers in diamonds in coupled-cavity systems are considered great candidates for the efficient generation of quantum carriers over other solid-state emitters. Owing to the multi-mode nature of high quality factor ( Q) diamond cavities, however, it is a grand challenge to the achievement of single photon emission with high rate and indistinguishability. To this end, a single-mode high- Q diamond cavity is highly desired. Here, we report a diamond mesostructured nanomembrane microcavity of a discrete rotational symmetry that selectively produces the desired single-mode emission in a broad spectrum. The strategic rolling up of a flexible diamond nanomembrane with aligned holes effectively defines the designed symmetry while maintaining the high- Q resonance through the whispering-gallery mode supported in the central hollow microcavity. The demonstrated diamond mesostructured microcavity features a distinct and enhanced single-mode emission, a step toward efficient quantum sources with designed positions or bands for quantum information technology.

Identification of Novel PI3Kδ Selective Inhibitors by SVM-Based Multistage Virtual Screening and Molecular Dynamics Simulations.

Phosphoinositide 3 kinase delta (PI3Kδ) is a lipid kinase that has been implicated in a variety of immune mediated disorders. The research on isoform selectivity was crucial for reducing side effects. In the current study, an optimized hierarchical multistage virtual screening method was utilized for screening the PI3Kδ selective inhibitors. The method sequentially applied a support vector machine (SVM), a protein ligand interaction fingerprint (PLIF) pharmacophore, and a molecular docking approach. The evaluation of the validation set showed a high hit rate and a high enrichment factor of 75.1% and 301.66, respectively. This multistage virtual screening method was then utilized to screen the NCI database. From the final hit list, Compound 10 has great potential as the PI3Kδ inhibitor with micromolar inhibition in the PI3Kδ kinase activity assay. This compound also shows selectivity against PI3Kδ kinase. The method combining SVM, pharmacophore, and docking was capable of screening out the compounds with potential PI3Kδ selective inhibitors. Moreover, structural modification of Compound 10 will contribute to investigating the novel scaffold and designing novel PI3Kδ inhibitors.

Study of Imidazolium Salt Derivatives as PIK3CA Inhibitors Using a Comprehensive in Silico Method.

A series of imidazolium salt derivatives have demonstrated potent antitumor activity in prior research. A comprehensive in silicon method was carried out to identify the putative protein target and detailed structure-activity relationship of the compounds. The Topomer CoMFA and CoMSIA techniques were implemented during the investigation to obtain the relationship between the properties of the substituent group and the contour map of around 77 compounds; the Topomer CoMFA and CoMSIA models were reliable with the statistical data. The protein-protein interaction network was constructed by combining the Pharmmapper platform and STRING database. After generating the sub-network, the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA with protein data bank ID: 3ZIM) was selected as the putative target of imidazolium salt derivatives. A docking study was carried out to correlate interactions of amino acids in protein active pockets surrounded by the ligand with contour maps generated by the structure-activity relationship method. Then the molecular dynamics simulations demonstrated that the imidazolium salt derivatives have potent binding capacity and stability to receptor 3ZIM, and the two ligand-receptor complex was stable in the last 2 ns. Finally, the ligand-based structure-activity relationship and receptor-based docking were combined together to identify the structural requirement of the imidazolium salt derivatives, which will be used to design and synthesize the novel PIK3CA inhibitors.