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In this study, a series of novel 4-Aryl-4H-chromene derivatives (D1-D31) were designed and synthesized by integrating quinoline heterocycle to crolibulin template molecule based on the strategy of molecular hybridization. One of these compounds D19 displayed positive antiproliferative activity against U87 cancer cell line (IC 50 = 0.90 ± 0.03 μM). Compound D19 was verified as the microtubule-targeting agent through downregulating tubulin related genes of U87 cells, destroying the cytoskeleton of tubulins and interacting with the colchicine-binding site to inhibit the polymerization of tubulins by transcriptome analysis, immune-fluorescence staining, microtubule dynamics and EBI competition assays as well as molecular docking simulations. Moreover, compound D19 induced G2/M phase arrest, resulted in cell apoptosis and inhibited the migration of U87 cells by flow cytometry analysis and wound healing assays. Significantly, compound D19 dose-dependently inhibited the tumor growth of orthotopic glioma xenografts model (GL261-Luc) and effectively prolonged the survival time of mice, which were extremely better than those of positive drug temozolomide (TMZ). Compound D19 exhibited potent in vivo antivascular activity as well as no observable toxicity. Furthermore, the results of in silico simulation studies and P-gp transwell assays verified the positive correlation between compound D19 's Blood-Brain Barrier (BBB) permeability and its in vivo anti-GBM activity. Overall, compound D19 can be used as a promising anti-GBM lead compound for the treatment of glioblastoma. [Display omitted] • Thirty-one 4-Aryl-4H-chromene derivatives were synthesized and investigated. • The compound D19 acted as the microtubule-targeting agent. • The compound D19 displayed excellent anti-glioblastoma activity in vivo. [ABSTRACT FROM AUTHOR]

• Fatigue crack evolution of asphalt mixture were analyzed by acoustic emission (AE) technique. • Fatigue damage in asphalt mixtures was categorized into four stages by AE parameters. • The evolution of AE b value was correlated with crack propagation. The identification and investigation of fatigue crack evolution and damage modes in asphalt mixtures are crucial for understanding the corresponding mechanisms and characteristics of fatigue failure. In this study, the four-point bending fatigue tests were performed on the asphalt mixture specimens with precast joints using the acoustic emission (AE) technique to analyze the damage evolution. The failure modes of the asphalt mixtures were identified using the Gaussian mixture model (GMM). The results revealed that the fatigue damage of the asphalt mixtures can be categorized into four stages: Stage I (void compaction), Stage II (microcrack initiation and stable propagation), Stage III (crack aggregation and unstable propagation), and Stage IV (complete fracture). This division was defined based on the inflection points of the axial displacement curves, the cumulative number of AE events, and the cumulative ringing counts. The evolution of the AE b value was found to be correlated with the crack propagation. The rapid decline in the b value in Stage III was considered a harbinger of the eventual complete fracture in the asphalt mixtures. The GMM clustering analysis indicated that the fatigue damage of the asphalt mixtures primarily involved tensile damage (90%), and shear damage made a small contribution of 10%. Existing AE studies have focused on the quantitative evaluation of AE parameters, while research on clustering identification algorithms for these parameters is scarce. The analytical methods and findings of this study enable an effective identification of fatigue damage in asphalt mixtures at the laboratory scale and offer insights into the fatigue damage mechanisms of asphalt mixtures. [ABSTRACT FROM AUTHOR]

PM 2.5 -bound toxic metals are hazardous to human health due to their bioaccumulation and non-degradability. To investigate the sources and health risks of PM 2.5 -bound toxic metals at urban Dongguan in the Pearl River Delta region, a comprehensive campaign was carried out in this city in 2019 to measure hourly mass concentrations of PM 2.5 -bound toxic metals (e.g., V, Cr, Mn, Ni, As and Pb). The annual average mass concentrations of V (2.4 ± 2.1 ng m−3), Mn (18.5 ± 12.1 ng m−3), Ni (1.9 ± 1.2 ng m−3), As (4.6 ± 3.8 ng m−3) and Pb (17.8 ± 15.4 ng m−3) met the guidelines proposed by the World Health Organization (WHO), while that of Cr(VI) (estimated as 1/7 of Cr, 0.66 ng m−3) was 2.6 times higher than the WHO guideline. Positive matrix factorization (PMF) analysis suggested that Cr (70 ± 23%) and Mn (54 ± 24%) mainly originated from non-exhaust emission, Ni (50 ± 29%) and V (83 ± 24%) from ship emission and As (54 ± 28%) and Pb (55 ± 28%) from coal combustion. The hazard index (HI) of PM 2.5 -bound toxic metals was 0.76, complying with the acceptable value of 1.0. The carcinogenic risks (CRs) associated with Cr(VI) and As for adults were 18.6 and 5.7 times higher than the threshold value of 1 × 10−6, respectively. However, the CRs for children were 3.5 and 0.5 times higher than the same threshold value, respectively. HI and CRs of these toxic metals were dominated by non-exhaust emission and coal combustion, suggesting emission reductions from these sources would effectively reduce the human health risks caused by toxic metals. [Display omitted] • The estimated Cr(VI) annual concentration exceeds the WHO guideline. • The carcinogenic risks of Cr(VI) and As exceeded the EPA threshold value. • Cr(VI) and As were mainly originated from non-exhaust emission and coal combustion. [ABSTRACT FROM AUTHOR]