TiO2/MXene-Assisted LDI-MS for Urine Metabolic Profiling in Urinary Disease

Cancer remains an intractable medical problem. Rapid diagnosis and identification of cancer are critical to differentiate it from nonmalignant diseases. High-throughput biofluid metabolic analysis has potential for cancer diagnosis. Nevertheless, the present metabolite analysis method does not meet the demand for high-throughput screening of diseases. Herein, a high-throughput, cost-effective, and noninvasive urine metabolic profiling method based on TiO₂/MXene-assisted laser desorption/ionization mass spectrometry (LDI-MS) is presented for the efficient screening of bladder cancer (BC) and nonmalignant urinary disease. Combined with machine learning, TiO₂/MXene-assisted LDI-MS enables high diagnostic accuracy (96.8%) for the classification of patient groups (including 47 BC and 46 ureteral calculus (UC) patients) from healthy controls (113 cases). In addition, BC patients can also be identified from noncancerous UC individuals with an accuracy of 88.3% in the independent test cohort. Furthermore, metabolite variations between BC and UC individuals are investigated based on relative quantification, and related pathways are also discussed. These results suggest that this method, based on urine metabolic patterns, provides a potential tool for rapidly distinguishing urinary diseases and it may pave the way for precision medicine.     

2-Phenyloxazole-4-carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (K_i) values in the sub-micromolar range and a good selectivity index (K_{i MAO-A}/K_{i MAO-B}>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity.     

Activity-Directed Synthesis: A Flexible Approach for Lead Generation

Activity-directed synthesis (ADS) is a structure-blind, functional-driven molecular discovery approach. In this Concept, four case studies highlight the general applicability of ADS and showcase its flexibility to support different medicinal chemistry strategies. ADS deliberately harnesses reactions with multiple possible outcomes, and allows many chemotypes to be evaluated in parallel. Resources are focused on bioactive molecules, which emerge in tandem with associated synthetic routes. Some of the future challenges for ADS are highlighted, including the realisation of an autonomous molecular discovery platform. The prospects for ADS to become a mainstream lead generation approach are discussed.     

基于ABAQUS的显式动力学分析方法研究

显式动力学(The Explicit Dynamic)是针对隐式求解器的一个补充,其分析方法对于求解广泛、各类非线性结构力学问题是一个非常有效的工具,显式方法中的单个增量步取决于模型的最高固有频率,与持续时间、载荷类型无关。ABAQUS/Explicit主要用于碰撞、接触以及失效分析。探讨了ABAQUS显式动力学的基本理论、求解的问题,对显示动力学分析方法中的求解算法、稳定时间极限和能量平衡问题进行研究,给出了显示动力学分析的一般性分析方法。通过案例验证了该方法的可行性,应用该方法可有效解决实际工业生产中的碰撞问题、复杂的接触问题以及复杂的后屈曲问题,可为显式动力学分析方法应用于工程实践奠定理论与方法基础。     

A modified cross-correlation algorithm for PIV image processing of particle-fluid two-phase flow

PIV (Particle Image Velocimetry) technique for flow field measurement has achieved popular self-identify through over ten years development, and its application range is becoming wider and wider. PIV post-processing techniques have a great influence on the success of particle-fluid two-phase flow field measurement and thus become a hot and difficult topic. In the present study, a Phase Respective Identification Algorithm (PRIA) is introduced to separate low-density solid particles or bubbles and high-density tracer particles from the PIV image of particle-fluid two-phase flow. PTV (Particle Tracking Velocimetry) technique is employed to calculate the velocity fields of low-density solid particles or bubbles. For the velocity fields of high-density solid particles or bubble phase and continuous phase traced by high-density smaller particles, based on the thought of wavelet transform and multi-resolution analysis and the theory of cross-correlation of image, a delaminated processing algorithm (MCCWM) is presented to conquer the limitation of conventional Fourier transform. The algorithm is firstly testified on synthetic two-phase flows, such as uniform steady flow, shearing flow and rotating flow, and the computational results from the simulated particle images are in reasonable agreement with the given simulated data. The algorithm is then applied to images of actual bubble-liquid two-phase flow and jet flow, and the results also confirmed that the algorithm proposed in the present study has good performance and reliability for post-processing PIV images of particle-fluid two-phase flow.     

Quantitative UPLC‐MS/MS analysis of chlorogenic acid derivatives in antioxidant fractionates from dandelion (Taraxacum officinale) root

While qualitative studies have identified chlorogenic acids in antioxidant extracts, particularly ethyl acetate‐derived extracts, of Taraxacum officinale, quantitative analysis of these phenolic compounds remains largely unreported for this species. In this study, bioactivity‐guided fractionation of an antioxidant crude ethyl acetate extract (DPPH = 295.481 ± 0.955 mg TE g^?1 extract) from T. officinale root resulted in a number of reverse‐phase fractions that demonstrated high antioxidant activity (DPPH = 1058.733–1312.136 mg TE g^?1 extract), stronger than that of the synthetic antioxidant Trolox^®. UPLC‐MS/MS screening of these fractions for the presence of selected mono‐ and di‐caffeoylquinic acids revealed large quantities of 1,5‐dicaffeoylquinic acid present in several fractions (853.052–907.324 μg mg^?1), respectively. Due to the antioxidant potency and high levels of 1,5‐dicaffeoylquinic acid observed in these fractions, it was concluded that specifically this chlorogenic acid derivative is a major contributor to the antioxidant efficacy of dandelion root.     

Electromagnetism-like algorithms for optimized tool path planning in 5-axis flank machining

Optimization of tool path planning using metaheuristic algorithms such as ant colony systems (ACS) and particle swarm optimization (PSO) provides a feasible approach to reduce geometrical machining errors in 5-axis flank machining of ruled surfaces. The optimal solutions of these algorithms exhibit an unsatisfactory quality in a high-dimensional search space. In this study, various algorithms derived from the electromagnetism-like mechanism (EM) were applied. The test results of representative surfaces showed that all EM-based methods yield more effective optimal solutions than does PSO, despite a longer search time. A new EM-MSS (electromagnetism-like mechanism with move solution screening) algorithm produces the most favorable results by ensuring the continuous improvement of new searches. Incorporating an SPSA (simultaneous perturbation stochastic approximation) technique further improves the search results with effective initial solutions. This work enhances the practical values of tool path planning by providing a satisfactory machining quality.     

Thermoplastic and low dielectric constants polyimides based on BPADA-BAPP

ABSTRACT

The thermoplastic and low dielectric constants polyimides were introduced. The polyimides were prepared by pyromellitic dianhydride (PMDA) or 4,4?-(4,4?-Isopropylidenediphenoxy)diphthalic anhydride (BPADA) as anhydride monomer and 4,4?-oxydianiline (ODA) or 2,2-bis(4-(4-aminephenoxy)phenyl)propane (BAPP) as amine monomer. The polyimides were well characterized by FT-IR, thermogravimetric analysis, dynamic thermomechanical analysis, dielectric measurement, and tensile test. The dielectric constants were 2.32–2.95 compared with 3.10 of ODA-PMDA polyimide, while partly polyimides were thermoplastic. The results indicated anhydride monomers, containing lateral methyl groups, made polyimides become thermoplastic. The results of molecular simulations via Materials Studio also proved this conclusion.     

New anti-ablation candidate for carbon/carbon composites: Preparation,composition and ablation behavior of Y2Hf2O7 coating under an oxyacetylene torch

Y₂Hf₂O₇ possesses low thermal conductivity and high melting point, which make it promising for a new anti-ablation material. For evaluating the thermal stability and the potential applications of Y₂Hf₂O₇ on anti-ablation protection of C/C composites, Y₂Hf₂O₇ ceramic powder was synthesized by solution combustion method and Y₂Hf₂O₇ coating was prepared on the surface of SiC coated C/C composites using SAPS. Results shown that the coating exhibits good ablation resistance under the heat flux of 2.4?MW/m² with the linear and mass ablation rates are 0.16?μm?s^?1 and ?0.028?mg?s^?1, respectively, after ablation for 40?s. With the prolonging of the ablation time, the increasing thermal stress causes the increase of cracks. Moreover, the chemical erosion from SiO₂ and the physical volatilization of low temperature molten products aggravate failure of the Y₂Hf₂O₇ coating.