Therapeutic Nucleus-Access BNCT Drug Combined CD47-Targeting Gene Editing in Glioblastoma

Glioblastoma is the most common brain primary malignant tumor with the highest mortality. Boron neutron capture therapy (BNCT) can efficiently kill cancer cells on the cellular scale, with high accuracy, short course and low side-effects, which is regarded as the most promising therapy for malignant brain tumors like glioma. As the keypoint of BNCT, all boron delivery agents currently in clinical use are beset by insufficient tumor uptake, especially in the tumor nucleus, which limits the clinical application of BNCT. In this study, nuclear targeting of boron is achieved by DOX-CB, consisting of doxorubicin (DOX) andcarborane (CB) utilizing the nuclear translocation property of DOX. The nucleus of GL261 cells takes up almost three times the concentration of boron required for BNCT. To further kill glioma and inhibit recurrence, a new multifunctional nanoliposome delivery system DOX-CB@lipo-pDNA-iRGDis constructed. It combines DOX-CB with immunotherapy strategy of blocking macrophage immune checkpoint pathway CD47-SIRPα by CRISPR-Cas9 system, coupling BNCT with immunotherapy simultaneously. Compared with clinical drug Borocaptate Sodium (BSH), DOX-CB@lipo-pDNA-iRGD significantly enhances the survival rate of tumor-bearing mice, reduces tumor stemness, and improves the prognosis. The excellent curative effect of this nanoliposome delivery system provides an insight into the combined treatment of BNCT.

Model Development and Transient Analysis of the HCPB BB BOP DEMO Configuration Using the Apros System Code

Extensive modeling and analytical work has been carried out considering the Helium-Cooled Pebble Bed Breeding Blanket (HCPB BB) Balance Of Plant (BOP) configuration of the Demonstration Power Plant (DEMO) using the Apros system code, developed by VTT Technical Research Centre of Finland Ltd. and Fortum. The integral plant model of the HCPB BB plant has been improved with respect to the blanket and steam generator models. Based on HCPB-BL2017 v1 data, reported in 2019, the blanket has been remodeled by separate Apros process components, dedicated to average inboard and outboard segments, where the power deposition scheme of the breeding units took into account the output of high-fidelity neutronic analyses. A new helical coil steam generator model has been developed for primary–secondary system coupling using CAD data provided by EUROfusion partner University of Palermo. Transient analyses have been performed with Apros on the plant configuration that utilizes a molten salt technology-based small Energy Storage System (ESS).

Multi-System Coupling DMi Hybrid Vehicle Modeling and Its Performance Analysis Based on Simulation

Key subsystems, such as driving resistance, component performance, and energy management strategy, determine the power performance and energy consumption of hybrid electric vehicles. Qin Plus performs excellently in fuel consumption due to its low driving resistance, high thermal efficiency of the engine, and multi-factor multi-mode energy management strategy. This article aims to explain the outstanding energy consumption of DMi vehicles by analyzing the driving resistance, component parameters of Qin Plus and introducing the drive modes selection and vehicle energy management strategy through multi-system modeling and simulation. The ultra-low fuel consumption of 3.8 L is obtained under the NEDC driving cycle and evaluated by the corresponding experiment.

Proportional–Resonant Controller Structure with Finite Gain for Three-Phase Grid-Tied Converters

The paper presents the study of a three-phase system coupling a DC power source to a power grid. This study, based on an FPGA, implements a real-time control system and digital models of the power circuit. The proposed proportional–resonant (P+R) controller with a modified structure was part of the system, which can be used as an alternative controller to traditional ones, e.g., in photovoltaic systems. Due to difficulties in implementing resonant controllers, a P+R with a new structure using a PI controller was elaborated. With an appropriate approach to the generation of phase current patterns, it is possible to set the reactive current and, thus, compensate for the reactive power. The operation of the system for typical operating conditions (e.g., system startup, change in preset load) was characterized and compared with a classical solution using a PI controller.

Transcriptional and translational responsiveness of the Neisseria gonorrhoeae type IV secretion system to conditions of host infections

The type IV secretion system of Neisseria gonorrhoeae translocates single-stranded DNA into the extracellular space, facilitating horizontal gene transfer and initiating biofilm formation. Expression of this system has been observed to be low under laboratory conditions, and multiple levels of regulation have been identified. We used a translational fusion of lacZ to traD , the gene for the type IV secretion system coupling protein, to screen for increased type IV secretion system expression. We identified several physiologically relevant conditions, including surface adherence, decreased manganese or iron, and increased zinc or copper, which increase gonococcal type IV secretion system protein levels through transcriptional and/or translational mechanisms. These metal treatments are reminiscent of the conditions in the macrophage phagosome. The ferric uptake regulator, Fur, was found to repress traD transcript levels, but to also have a second role, acting to allow TraD protein levels to increase only in the absence of iron. To better understand type IV secretion system regulation during infection, we examined transcriptomic data from active urethral infection samples from five men. These data demonstrated differential expression of 20 of 21 type IV secretion system genes during infection, indicating upregulation of genes necessary for DNA secretion during host infection.