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Objective To construct vitamin E (tocopherol, VE)-based liposomes with both hydrogen peroxide-scavenging function and anticoagulant effect, and explore whether they can be used to treat acute ischemic stroke and then evaluate their in vitro anticoagulant effect. Methods Two molecules of VE were chemically bonded through peroxalate bond to obtain oxalate vitamin E (OVE). The anticoagulant unit LA-Hirudin was obtained by amidation reaction by connecting the anticoagulant drug hirudin to linoleic acid (LA). The structures of the synthesized products were characterized by using H nuclear magnetic resonance (1HNMR) and FT-IR spectra. Hirudin-Oxalic acid divitamin E ester liposome (HOL) was prepared by thin film dispersion and characterized with dynamic light scattering (DLS) and transmission electron microscopy (TEM). Mouse brain-derived endothelial cells (bEnd3) and human umbilical vein endothelial cells (HUVEC) were applied as the object of cell experiments. The levels of H2O2, and cellular inflammatory factors TNF-α, IL-6 and IL-1β were determined by ELISA to evaluate the effect of the liposomes on the severity of cellular inflammation. Cell counting kit-8 (CCK-8) assay and cell proliferation assay (5-Ethynyl-2′-deoxyuridine, Edu) were used to detect the effects of the liposomes on cell count and proliferation. The anticoagulant effect of the prepared liposomes was detected by using whole blood of mice. Results 1HNMR spectrum showed that OVE was successfully synthesized, and the FT-IR spectrum displayed that hirudin and linoleic acid were successfully bonded to obtain LA-Hirudin. The results of DLS and TEM indicated that the prepared liposomes were spheroids, in uniform distribution, with an average particle size of 161 nm. The cell experiments showed that the liposomes significantly inhibited the secretion of H2O2 and inflammatory factors, and exerted obvious antioxidant and anti-inflammatory effects in the model cells (P < 0.05). CCK-8 assay and Edu proliferation assay proved that the liposomes suppressed the decreased cell count and alleviated the inhibited cell proliferation caused by LPS (P < 0.01). Anticoagulation experiment revealed that the liposomes had significant inhibitory effect of CaCl2-induced coagulation reaction (P < 0.01). Conclusion A hydrogen peroxide-scavenging function material, OVE is synthesized, and then anticoagulant drug hirudin and OVE are used to prepare OVE thrombolytic liposomes, HOL. The liposomes have antioxidant and anti-inflammatory effects at the cellular level and also have significant anticoagulant effect.

In order to overcome the disadvantage of vehicle ride comfort caused by large vibration and torque excitation of vehicle engine in start/stop mode, a flow mode magneto-rheological (MR) mount is designed for low frequency working conditions. Based on the analysis on the influence of exciting current on the viscosity of the MR fluid (MRF) and the relationship between the fluid resistance effect and the flow rate in the damping channel, the magnetic circuit and the damping performance of the MR mount model are analyzed. According to the mathematical model of the MR mount damping force, the multi-objective optimization function of the magnetic circuit is established. The co-simulation optimal platform is developed by using the Isight and ANSYS software. The non-dominated sorting genetic algorithm II (NSGA-II) is used to optimize magnetic circuit design. The dynamic performance test of the MR mount monomer and the vibration isolation performance test of the whole vehicle in start/stop mode are conducted respectively. The results show that the controllable damping force of the optimized MR mount increases by 111.71% and the restoring force increases by 21.99% compared with those before. When the vehicle is in start/stop mode and the excitation current is 1.0A, the peak vibration acceleration of the passive side (the side connected to the body) with the optimized MR mount decreases by 33.3% compared with that before. Besides, the peak vibration acceleration of driver’s seat rail decreases by 21.6%, which significantly improves the ride comfort of the vehicle.

For achieving well-performing optical thermometry, a new type of dual-mode optical thermometer is explored based on the valley-to-peak ratio (VPR) and fluorescence lifetime of Eu3+ emissions in the ZrO2:Eu3+ nanocrystals with sizes down to 10 nm. In the VPR strategy, the intensity ratio between the valley (600 nm) generated by the emission band overlap and the 606 nm peak (5D0→7F2), which is highly temperature sensitive, is employed, giving the maximum relative sensing sensitivity (Sr) of 1.8% K−1 at 293 K and good anti-interference performance. Meanwhile, the 606 nm emission exhibits a temperature-dependent decay lifetime with the highest Sr of 0.33% K−1 at 573 K, which is due to the promoted nonradiative relaxation with temperature. These results provide useful information for constructing high-performance dual-mode optical thermometers, which may further stimulate the development of photosensitive nanomaterials for frontier applications.

C18H18N2O6, monoclinic, P21/n (no. 14), a = 7.4809(14) Å, b = 13.082(2) Å, c = 16.870(3) Å, β = 93.440(4)°, V = 1648.0(5) Å3, Z = 4, Rgt(F) = 0.0433, wRref(F2) = 0.1279, T = 296(2) K.

The Type IV Secretion System (T4SS) is the only bacterial secretion system known to translocate both DNA and protein substrates. The VirB/D4 system from Agrobacterium tumefaciens is a typical T4SS. It facilitates the bacteria to translocate the VirD2-T-DNA complex to the host cell cytoplasm. In addition to protein-DNA complexes, the VirB/D4 system is also involved in the translocation of several effector proteins, including VirE2, VirE3 and VirF into the host cell cytoplasm. These effector proteins aid in the proper integration of the translocated DNA into the host genome. The VirD2-binding protein (VBP) is a key cytoplasmic protein that recruits the VirD2-T-DNA complex to the VirD4-coupling protein (VirD4 CP) of the VirB/D4 T4SS apparatus. Here, we report the crystal structure and associated functional studies of the C-terminal domain of VBP. This domain mainly consists of α-helices, and the two monomers of the asymmetric unit form a tight dimer. The structural analysis of this domain confirms the presence of a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) fold. Biophysical studies show that VBP is a dimer in solution and that the HEPN domain is the dimerization domain. Based on structural and mutagenesis analyses, we show that substitution of key residues at the interface disrupts the dimerization of both the HEPN domain and full-length VBP. In addition, pull-down analyses show that only dimeric VBP can interact with VirD2 and VirD4 CP. Finally, we show that only Agrobacterium harboring dimeric full-length VBP can induce tumors in plants. This study sheds light on the structural basis of the substrate recruiting function of VBP in the T4SS pathway of A. tumefaciens and in other pathogenic bacteria employing similar systems.