Tumor cells disseminate to distant organs mainly through blood circulation in which they experience considerable levels of fluid shear stress. However, the effects of hemodynamic shear stress on biophysical properties and functions of circulating tumor cells (CTCs) in suspension are not fully understood. In this study, we found that the majority of suspended breast tumor cells could be eliminated by fluid shear stress, whereas cancer stem cells held survival advantages over conventional cancer cells. Compared to untreated cells, tumor cells surviving shear stress exhibited unique biophysical properties: 1) cell adhesion was significantly retarded, 2) these cells exhibited elongated morphology and enhanced spreading and expressed genes related to epithelial-mesenchymal transition or hybrid phenotype, and 3) surviving tumor cells showed reduced F-actin assembly and stiffness. Importantly, inhibiting actomyosin activity promoted the survival of suspended tumor cells in fluid shear stress, whereas activating actomyosin suppressed cell survival, which might be explained by the up-and downregulation of the antiapoptosis genes. Soft surviving tumor cells held survival advantages in shear flow and higher resistance to chemotherapy. Inhibiting actomyosin activity in untreated cells enhanced chemoresistance, whereas activating actomyosin in surviving tumor cells suppressed this ability. These findings might be associated with the corresponding changes in the genes related to multidrug resistance. In summary, these data demonstrate that hemodynamic shear stress significantly influences biophysical properties and functions of suspended tumor cells. Our study unveils the regulatory roles of actomyosin in the survival and drug resistance of suspended tumor cells in hemodynamic shear flow, which suggest the importance of fluid shear stress and actomyosin activity in tumor metastasis. These findings may reveal a new, to our knowledge, mechanism by which CTCs are able to survive hemodynamic shear stress and chemotherapy and may offer a new potential strategy to target CTCs in shear flow and combat chemoresistance through actomyosin.

A highly efficient bimetallic Cu−Ni catalytic system for selective hydrogenation of levulinic acid/ester to 2-methyltetrahydrofuran (2-MTHF) promoted by the solvent was presented. A 98% yield of 2-MTHF was achieved with optimal 10Cu-5Ni/ Al 2 O 3 catalyst at a mild temperature in the presence of nonpolar organic solvent n-hexane and molecular hydrogen. A mechanistic study revealed a synergistic effect between Cu and Ni nanoparticles, wherein Ni primarily activated H 2 and hydrogenated levulinic acid/ester to GVL and Cu facilitated the hydrogenation of GVL to 2-MTHF. Detailed studies on solvent effects revealed that the n-hexane possessed higher H 2 dissolvability and enhanced adsorption of GVL on the catalyst surface to facilitate its conversion to 2-MTHF, providing a lower apparent activation energy barrier of 48.9 kJ/mol for the rate-determining step. DFT calculations also indicated a highest adsorption energy of GVL with Al 2 O 3 over other substrates and solvent molecules, further highlighting the promotion effect of nonpolar n-hexane solvent.

Odorant binding proteins (OBPs) and chemosensory proteins (CSPs) play important roles in transporting semiochemicals through the sensillar lymph to olfactory receptors in insect antennae. In the present study, twenty OBPs and three CSPs were identified from the antennal transcriptome of Microplitis mediator. Ten OBPs (MmedOBP11–20) and two CSPs (MmedCSP2–3) were newly identified. The expression patterns of these new genes in olfactory and non-olfactory tissues were investigated by real-time quantitative PCR (qPCR) measurement. The results indicated that MmedOBP14, MmedOBP18, MmedCSP2 and MmedCSP3 were primarily expressed in antennae suggesting potential olfactory roles in M. mediator. However, other genes including MmedOBP11–13, 15–17, 19–20 appeared to be expressed at higher levels in body parts than in antennae. Focusing on the functional characterization of MmedCSP3, immunocytochemistry and fluorescent competitive binding assays were conducted indoors. It was found that MmedCSP3 was specifically located in the sensillum lymph of olfactory sensilla basiconca type 2. The recombinant MmedCSP3 could bind several types of host insects odors and plant volatiles. Interestingly, three sex pheromone components of Noctuidae insects, cis-11-hexadecenyl aldehyde (Z11-16: Ald), cis-11-hexadecanol (Z11-16: OH), and trans-11-tetradecenyl acetate (E11-14: Ac), showed high binding affinities (Ki = 17.24–18.77 μM). The MmedCSP3 may be involved in locating host insects. Our data provide a base for further investigating the physiological roles of OBPs and CSPs in M. mediator, and extend the function of MmedCSP3 in chemoreception of M. mediator.

Odorant binding proteins (OBPs) are believed to be important for transporting semiochemicals through the aqueous sensillar lymph to the olfactory receptor cells within the insect antennal sensilla. In this study, three new putative OBP genes, MmedOBP8-10, were identified from a Microplitis mediator (Hymenoptera: Braconidae) antennal cDNA library. Quantitative real-time PCR (qRT-PCR) analysis revealed that all three of the OBP genes were expressed mainly in the antennae of adult wasps. The three OBPs were recombinantly expressed in Escherichia coli and purified by Ni ion affinity chromatography. Fluorescence competitive binding assays were performed using N-phenyl-naphthylamine as a fluorescent probe and 45 small organic compounds as competitors. These assays demonstrated that the three M. mediator OBPs can bind a broad range of odorant molecules with different binding affinities. They can bind the following ligands: nonane, farnesol, nerolidol, nonanal, β-ionone, acetic ether, and farnesene. In a Y-tube assay with these ligands as odor stimuli and paraffin oil as a control, all ligands, except nerolidol and acetic ether, were able to elicit behavioral responses in adult M. mediator. The wasps were significantly attracted to β-ionone, nonanal, and farnesene and repelled by nonane and farnesol. The results of this work provide insight into the chemosensory functions of the OBPs in M. mediator.