Search

Background Recently, many strategies have emerged to develop the conventional treatment of hepatocellular carcinoma (HCC). Previously, we have established an HCC targeting system of conditionally replicative adenovirus (CRAd) delivered by human umbilical cord-derived mesenchymal stem cells (HUMSCs). At present, the system needs to be developed for enhancing anti-tumor effect and overcoming limitation caused by alpha-fetoprotein (AFP) heterogeneity of HCC. Methods A bispecific T cell engager (BiTE) targeting programmed death ligand 1 (PD-L1) controlled by human telomerase reverse transcriptase (hTERT) promoter was armed on the CRAd of old system. A series of experiments in vitro such as ELISA, flow cytometry, electron microscope and so on were performed for identification of the novel system. Then the anti-tumor effect was explored on orthotopic transplantation model mice and AFP heterogeneous model mice by bioluminescent imaging and the side effects were assessed by levels of serum AST and ALT and HE staining for extrahepatic organs. The distributions of CRAd and BiTE in tumor tissue were detected using confocal microscope and the intratumoral T cell was analyzed by flow cytometry. Results Firstly, the characters of the new system including the selective killing activity of CRAd, the release of BiTE and the CRAd package and delivery by HUMSC were identified. And then the result on orthotopic transplantation model mice showed that the new system had better anti-tumor activity and less hepatotoxicity than the old. In the tumor tissue of model mice treated by the new system, the infiltration and activation of T cells were significantly enhanced. Lastly, the new system could eliminate the AFP negative cells in AFP heterogeneous tumor efficiently. Conclusions Comparing the old system, the new provides a more effective and safer strategy against HCC.

The electro-osmotic flow of Oldroyd-B fluids in a 90° curved tube with a rectangular section under a direct electric field is numerically studied. By introducing elastic forces into the force balance of viscous, electric, and centrifugal forces, another secondary flow pattern is found in addition to the stable state for Newtonian fluids, i.e., the periodic oscillation state. In this oscillating state, the position of the maximum velocity periodically moves from the center to the position near the wall. Meanwhile, a symmetric vortex can be periodically observed in the streamline figures. The secondary flow oscillates when the Deborah number De or the dimensionless wall potential [Formula: see text] is sufficiently large, and the oscillating frequency increases with a larger Deborah number De or a larger dimensionless wall potential [Formula: see text]. A phase diagram of the secondary flow as it depends on the Deborah number De and the dimensionless wall potential [Formula: see text] is presented. There is a critical Deborah number [Formula: see text] for a given wall potential [Formula: see text], and the secondary flow become periodically oscillating at [Formula: see text]. The critical Deborah number [Formula: see text] decreases as the value of the dimensionless wall potential [Formula: see text] increases. Moreover, the critical Deborah number should be larger than 0.2 even though the wall potential [Formula: see text] further increases, i.e., [Formula: see text]. At [Formula: see text], the elastic forces are small, and the secondary flow is stable rather than oscillating similar to the phenomena of Newtonian fluids.

Multiple myeloma (MM) is a B-cell malignancy for which new treatments are urgently needed. Redirecting the activity of T cells by bispecific antibodies against tumor cells is a potent approach. The B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein and therefore is an ideal therapeutic target for T-cell redirecting therapies. The main objective of this work is to target the BCMA by generating BCMA-specific murine monoclonal antibody and construct a cluster of differentiation 3 (CD3)/BCMA-directed tandem diabodies (Tandab). In brief, using standard hybridoma technology, we developed a novel BCMA-specific monoclonal antibody (clone 69G8), that specifically bind with BCMA+ cell lines and MM patient sample; whereas BCMA- cells were not recognized. For T cells by bispecific antibodies application, we constructed a Tandab (CD3/BCMA) simultaneously targeting both CD3 and BCMA and our studies demonstrated that Tandab (CD3/BCMA) was functional with specific binding capability both for CD3+ cells and BCMA+ cells. It induced selective, dose-dependent lysis of BCMA+ cell lines, activation of T cells, release of cytokines and T-cell proliferation; whereas BCMA- cells were not affected. Furthermore, we demonstrated that Tandab activity correlates with BCMA expression, with higher potency observed in highly BCMA expressing tumor cells. In vivo, the purified Tandab (CD3/BCMA) significantly inhibited the tumor growth in a subcutaneous NCI-H929 xenograft model. Taken together, these results show that the Tandab (CD3/BCMA) displays potent and selective anti-MM activities and represents a promising immunotherapeutic for the treatment of MM.

Functional platinum-based carbonous nanostructures play important roles in exploring new electrode materials by constructing sensitive and selective platform in the electrochemical detection. In recent years, intense research efforts have focused on boosting the performance of platinum with desirable activity and stability. This work reports a facile strategy for the synthesis of platinum-based nitrogen-doped porous C x N 1-x compounds (Pt-pC x N 1-x ) with excellent enzyme-like activity. In the strategy, Pt-pC x N 1-x was simply prepared by in situ synthesis through a one-step microwave-assisted heating procedure, resulting with subnanometer-size (∼2.5 nm) platinum-based nanoparticles (Pt-BNPs) loaded on the multi-dimensional C x N 1-x structure. Due to the enriched edge and corner atoms, Pt-pC x N 1-x showed excellent intrinsic peroxidase-like activity. Meanwhile, it was demonstrated that Pt-pC x N 1-x possessed a lower Michaelis Constant ( K m = 0.104) compared with horseradish peroxidase (HRP) ( K m = 0.416) in the presence of 3,3,5,5-tetramethylbenzidine (TMB) and hydrogen peroxide (H 2 O 2 ). Moreover, the Pt-pC x N 1-x behaved better property and lower cost in H 2 O 2 electrochemical detection compared with the pC x N 1-x and Pt-BNPs. The detection results exhibited a low detection limit (2.29 μM) and a wide linear range (0.025 to 5.725 mM), which revealed its superior potential in H 2 O 2 electrochemical detection. Therefore, the Pt-pC x N 1-x may find a potential application in constructing electrochemical biosensors.

Improving the performance of conventional enzyme-linked immunosorbent assay (ELISA) is of great importance to meet the demand of early clinical diagnosis of various diseases. Herein, we report a feasible enzyme-free immunosorbent assay (EFISA) system using antibody conjugated Au-Pt/SiO2 nanocomposites (APS NCs) as labels. In this system, Au-Pt/SiO2 nanospheres (APS NPs) were first synthesized by wet chemical method and exhibited intrinsic peroxidase and catalase-like activity with excellent water-solubility. Then APS NCs were utilized as labels to replace HRP conjugated antibody, and Fe3O4 magnetic beads (MBs) to entrap the analyte. To discuss the performance of EFISA system, Human IgG was served as a model analyte, and porcine circovirus type 2 (PCV2) serums as real samples. The system boosted the detection limit of HIgG to 75pgmL(-1) with a RSD below 5%, a 264-fold improvement as compared with conventional ELISA. This is the first time that APS NCs have been used and successfully optimized for the sensitive dilution detection of PCV2 antibody (5:10(7)) in ELISA. Besides, APS NCs have advantages related to low cost, easy preparation, good stability and tunable catalytic activity, which make them a potent enzyme mimetic candidate and may find potential applications in bioassays and clinical diagnostics.

Control of structure-enriched abundant unsaturated or dangling bonds can precisely and effectively tune the activity and durability of materials. In this study, a new strategy to obtain fusiform nanoarchitectures (FNAs) has been found for the first time using Te nanostructures as the model materials. TeFNA could be transformed from Te nanorods (NRs) with different diameter (50, 25 nm), even the ultrathin nanowires (NWs) (10 nm). Besides, a novel perspective into the preliminary mechanism combining collision theory with density functional theory simulations was proposed to explain the transformation progress. In the mixing system of hexadecyl trimethylammonium bromide (CTAB) solution, the Te NR/NWs keep the translational motion together with the centroid rotation. The velocity of the two ends of TeNR/NWs is higher than that in the center under the reaction condition based on collision theory; meanwhile, the summation energy of both O2 and CTAB put on Te (0001) surface is −606.992 eV, which means that the T...

Sr3SiO5 phosphors co-doped with Eu2+ and Tb3+ were prepared by a conventional solid-state reaction method. The prepared Sr3SiO5:Eu2+,Tb3+,Li+ phosphors had characteristic luminescent spectra excited under near-UV excitation in which both the broadband spectrum assigned to Eu2+ and the line spectrum assigned to Tb3+ are observed, although Tb3+ is inactive with this photon energy in general. For Eu2+–Tb3+ codoped Sr3SiO5, energy transfer process takes place and the mechanism is ascribed to the overlap between the shorter Eu2+ luminescence band from the Sr3SiO5 crystal structure with two Sr sites and 5D4 energy level of Tb3+ ion. Due to the energy transfer, PL intensity of Eu2+ emission increased about 26 %. We suggest that this enhancement mechanism could shed light on the potential applications in white light-emitting diodes excited by near-UV light. In addition, the emission peak position near the orange region indicates that our system is a step towards a new class of wavelength sources for artificial lighting with improved PL intensity and lower energy consumption.

A novel and green multifunctional nanoplatform as a nanocarrier for drug delivery, cell imaging, and phototherapy has been engineered. The nanoplatform is composed of stabilized carbon spheres (CSs) as cores, a coated polydopamine (PDA) shell, targeted folic acid (FA), and the loaded anticancer drug indocyanine green (ICG), obtaining CSs@PDA-FA@ICG nanocomposites (NCs). The biocompatible PDA shell provided a high fluorescence quenching efficiency and a surface rich in functional groups for anchoring FA for targeting cancer cells. Aromatic ICG could be effectively loaded into the CSs@PDA-FA system via hydrophobic interactions and π-π stacking with a loading efficiency of 58.9%. Notably, the activated NIR fluorescence in an intracellular environment made CSs@PDA-FA@ICG a sensitive "OFF" to "ON" nanoprobe that can be used for NIR imaging. Moreover, compared to ICG alone, the CSs@PDA-FA@ICG NCs could induce efficient photoconversion for simultaneous synergetic photodynamic therapy (PDT) and photothermal therapy (PTT) under a single NIR laser irradiation. The results demonstrated that CSs@PDA-FA@ICG NCs as a targeted and activated nanoplatform provide new opportunities to facilitate the accurate diagnosis of cancer and enhanced treatment efficacy. This work stimulates more interest in the design of the facile surface functionalization strategy to construct other multifunctional nanocomposites, such as nanotubes and nanorods.

In this work, a high-capacity supercapacitor material based on functionalized three-dimensional (3D) porous graphene was fabricated by low temperature hydrothermal treatment of graphene oxide (GO) using both ionic liquid (IL) and SiO2 spheres as "spacers". In the synthesis, the introduction of dual "spacers" effectively enlarged the interspace between graphene sheets and suppressed their re-stacking. In addition, the IL also acted as a structure-directing agent playing a crucial role in inducing the formation of unique 3D architectures. Consequently, fast electron/ion transport channels were successfully constructed and numerous oxygen-containing groups on graphene sheets were effectively reserved, which had unique advantages in decreasing ion diffusion resistance and providing additional pseudocapacitance. As expected, the obtained material exhibited superior specific capacitance and rate capability compared to single "spacer" designed electrodes and simultaneously maintained excellent cycling stability. In particular, there was nearly no loss of its initial capacitance after 3000 cycles. In addition, we further assembled a symmetric two-electrode device using the material, which showed outstanding flexibility and low equivalent series resistance (ESR). More importantly, it was capable of yielding a maximum power density of about 13.3 kW kg(-1) with an energy density of about 7.0 W h kg(-1) at a voltage of 1.0 V in 1 M H2SO4 electrolyte. All these impressive results demonstrate that the material obtained by this approach is greatly promising for application in high-performance supercapacitors.

With the creation named Matrilocal Dog, Yoko Yawada won the Akuta Kawa Prize and became known to the public. Interlacing the reality and irreality, the story tells about the relationship between Mitsuko Kitamura, who works as a teacher in a private school and Tarou, a man turned from a dog. This paper will analyze the artistic charm mainly from the story’s technique of creation.