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Metastasis is the main cause of mortality in patients with cancer. Epithelial–mesenchymal transition (EMT), a crucial process in cancer metastasis, is an established target for antimetastatic drug development. LFG-500, a novel synthetic flavonoid, has been revealed as a potential antitumor agent owing to its various activities, including modulation of EMT in the inflammatory microenvironment. Here, using a transforming growth factor beta (TGF-β)-induced EMT models, we found that LFG-500 inhibited EMT-associated migration and invasion in human breast cancer, MCF-7, and lung adenocarcinoma, A549, cell lines, consistent with the observed downregulation of YAP activity. Further studies demonstrated that LGF-500-induced suppression of YAP activation was mediated by integrin-linked kinase (ILK), suggesting that the ILK/YAP axis might be feasible target for anti-EMT and antimetastatic treatments, which was verified by a correlation analysis with clinical data and tumor specimens. Hence, our data support the use of LGF-500 as an antimetastatic drug in cancer therapy and provide evidence that the ILK/YAP axis is a feasible biomarker of cancer progression and a promising target for repression of EMT and metastasis in cancer therapy.

The self-healing properties of ultra-high toughness fly ash based geopolymer curing in air and water were studied under 2% pre-tension strain. The experimental results show that under these two curing conditions the tensile stress and water absorption of FA-EGC have been recovered and the pore structure has also been improved, indicating that self-healing has taken place in the specimens. Compared to the air environment, the water environment is proved to be a better environment for the self-healing of FA-EGC. It was observed that there were unreacted fly ash particles at the cracks through SEM. And more N-A-S-H gels were found under the water environment, indicating that N-A-S-H gels may enhance the fiber/matrix interface and improve the density of the matrix, resulting in the higher recovery of tensile stress and water absorption.

The formation and maintenance of synapses require long-distance delivery of newly synthesized synaptic proteins from the soma to distal synapses, raising the fundamental question of whether impaired transport is associated with neurodevelopmental disorders such as autism. We previously revealed that syntabulin acts as a motor adapter linking kinesin-1 motor and presynaptic cargos. Here, we report that defects in syntabulin-mediated transport and thus reduced formation and maturation of synapses are one of core synaptic mechanisms underlying autism-like synaptic dysfunction and social behavioral abnormalities. Syntabulin expression in the mouse brain peaks during the first 2 weeks of postnatal development and progressively declines during brain maturation. Neurons from conditional syntabulin−/−mice (stbcKO) display impaired transport of presynaptic cargos, reduced synapse density and active zones, and altered synaptic transmission and long-term plasticity. Intriguingly, stbcKO mice exhibit core autism-like traits, including defective social recognition and communication, increased stereotypic behavior, and impaired spatial learning and memory. These phenotypes establish a new mechanistic link between reduced transport of synaptic cargos and impaired maintenance of synaptic transmission and plasticity, contributing to autism-associated behavioral abnormalities. This notion is further confirmed by the human missense variant STB-R178Q, which is found in an autism patient and loses its adapter capacity for binding kinesin-1 motors. Expressing STB-R178Q fails to rescue reduced synapse formation and impaired synaptic transmission and plasticity in stbcKO neurons. Altogether, our study suggests that defects in syntabulin-mediated transport mechanisms underlie the synaptic dysfunction and behavioral abnormalities that bear similarities to autism.

Nucleic acids generally reside in cellular aqueous solutions with mixed divalent/monovalent ions, and the competitive binding of divalent and monovalent ions is critical to the structures of nucleic acids because of their polyanionic nature. In this work, we first proposed a general and effective method for simulating a nucleic acid in mixed divalent/monovalent ion solutions with desired bulk ion concentrations via molecular dynamics (MD) simulations and investigated the competitive binding of Mg2+/Na+ions to various nucleic acids by all-atom MD simulations. The extensive MD-based examinations show that single MD simulations conducted using the proposed method can yield desired bulk divalent/monovalent ion concentrations for various nucleic acids, including RNA tertiary structures. Our comprehensive analyses show that the global binding of Mg2+/Na+to a nucleic acid is mainly dependent on its structure compactness, as well as Mg2+/Na+concentrations, rather than the specific structure of the nucleic acid. Specifically, the relative global binding of Mg2+over Na+is stronger for a nucleic acid with higher effective surface charge density and higher relative Mg2+/Na+concentrations. Furthermore, the local binding of Mg2+/Na+to a phosphate of a nucleic acid mainly depends on the local phosphate density in addition to Mg2+/Na+concentrations.

Luminescent lanthanide metal–organic frameworks (Ln-MOFs) draw great interest due to their promising luminescent properties and wide applications in sensor design. In this work, a europium-organic framework (DPQ-Eu) has been synthesized under solvothermal conditions based on the aggregation-induced emission (AIE) ligand 4, 4′-(quinoxaline-2, 3-diyl)dibenzoic acid (H2DPQ). Structural analyses show that DPQ-Euadopts the monoclinic C2/c space group and forms a 3, 6-connected 2D porous network with a topological symbol of {42·6}2{44·69·82}. The formation of DPQ-Eucontributes an absolute quantum efficiency of 21.49% compared with that of the AIE ligand H2DPQ(0.02%) mainly due to the coordination-induced emission, providing DPQ-Euwith a great potential of being a luminescent sensor. Fluorescent investigations show that DPQ-Euhas a selective and sensitive response to Fe3+and Hg2+among various metal ions by ratiometric emission changes of the decreased emission at 415 nm and increased emission at 676 nm, with the detection limits of 25.99 and 39.70 nM and good reusability (5 times). The sensing behaviors probably can be ascribed to the promoted antenna effect from the ligand to the Eu(III) center by the coordination of Fe3+/Hg2+to the quinoxaline moiety. For anion sensing, DPQ-Eucan respond to Cr2O72–by emission quenching at both 415 and 676 nm with a detection limit of 9.88 nM and 5 times reusability, probably associated with the energy competing absorption and reduced energy transfer from the ligand to the Eu(III) center. In addition, DPQ-Eushows ratiometric emission changes to CN–by the emission enhancement and decrease at 415 and 676 nm, respectively, with a detection limit of 8.19 nM and five-run recycling tests, probably corresponding to the inhibition of energy transfer from the ligand to the Eu(III) center caused by the binding interactions between the CN–and Eu(III) nodes.

A microfluidic system is designed to fabricate polymer dispersed liquid crystal microspheres, whose shape, surface smoothness, and size are controlled. A microlens array (MLA) is constructed by the assembly of the monodispersed microspheres. In the MLA, each microsphere acts as a separate imaging unit. As the liquid crystal (LC) used is a mixed liquid crystal that contain photoresponsive 4‐butyl‐4‐methoxyazobenzene, the imaging capability and light transportation of the MLA can be reversibly controlled by light irradiation.