A respiratory syncytial virus (RSV) vaccine based on parainfluenza virus 5 (PIV5)

AbstractHuman respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease and hospitalizations in infants and young children. It also causes significant morbidity and mortality in elderly and immune compromised individuals. No licensed vaccine currently exists. Parainfluenza virus 5 (PIV5) is a paramyxovirus that causes no known human illness and has been used as a platform for vector-based vaccine development. To evaluate the efficacy of PIV5 as a RSV vaccine vector, we generated two recombinant PIV5 viruses – one expressing the fusion (F) protein and the other expressing the attachment glycoprotein (G) of RSV strain A2 (RSV A2). The vaccine strains were used separately for single-dose vaccinations in BALB/c mice. The results showed that both vaccines induced RSV antigen-specific antibody responses, with IgG2a/IgG1 ratios similar to those seen in wild-type RSV A2 infection. After challenging the vaccinated mice with RSV A2, histopathology of lung sections showed that the vaccines did not exacerbate lung lesions relative to RSV A2-immunized mice. Importantly, both F and G vaccines induced protective immunity. Therefore, PIV5 presents an attractive platform for vector-based vaccines against RSV infection

The Effects of Chemical Oxidation and High-Temperature Reduction on Surface Functional Groups and the Adsorption Performance of Biochar for Sulfamethoxazole Adsorption

Biochar is a beneficial adsorbent for the treatment of organic pollutants in the environment. The association of oxygen functional groups and adsorption behaviors has not been well investigated. In this paper, the oxidation-modified biochar (O-BC) and the reduction-modified biochar (R-BCX) were prepared by Co2+/peroxymonosulfate chemical oxidation and high-temperature reduction, respectively. The modified biochars were used to remove sulfamethoxazole (SMX) from water, and the adsorption amounts of biochar followed the order of R-BC700 (14.66 mg·L−1) > O-BC (4.91 mg·L−1) > BC (0.16 mg·L−1). Additionally, the effects of water chemical conditions (i.e., ionic strength, solution pH and humic acid (HA) concentration) on the adsorption of SMX on biochar, were further investigated. Combining physical adsorption, X-ray electron spectroscopy, and zeta potentiometer characterization techniques, the effect of functional groups on the adsorption mechanism was further explored, revealing the importance of various oxygen functional groups for SMX adsorption. The results showed that C=O and C=C, resulting in π–π interaction, were in favor of the adsorption of SMX, while C-O was not conducive to the adsorption of SMX, due to the steric hindrance and the negative surface charge. Additionally, the hydrophobic effect of the biochar was also one of the adsorption mechanisms

The Effects of Chemical Oxidation and High-Temperature Reduction on Surface Functional Groups and the Adsorption Performance of Biochar for Sulfamethoxazole Adsorption

Biochar is a beneficial adsorbent for the treatment of organic pollutants in the environment. The association of oxygen functional groups and adsorption behaviors has not been well investigated. In this paper, the oxidation-modified biochar (O-BC) and the reduction-modified biochar (R-BCX) were prepared by Co2+/peroxymonosulfate chemical oxidation and high-temperature reduction, respectively. The modified biochars were used to remove sulfamethoxazole (SMX) from water, and the adsorption amounts of biochar followed the order of R-BC700 (14.66 mg·L−1) > O-BC (4.91 mg·L−1) > BC (0.16 mg·L−1). Additionally, the effects of water chemical conditions (i.e., ionic strength, solution pH and humic acid (HA) concentration) on the adsorption of SMX on biochar, were further investigated. Combining physical adsorption, X-ray electron spectroscopy, and zeta potentiometer characterization techniques, the effect of functional groups on the adsorption mechanism was further explored, revealing the importance of various oxygen functional groups for SMX adsorption. The results showed that C=O and C=C, resulting in π–π interaction, were in favor of the adsorption of SMX, while C-O was not conducive to the adsorption of SMX, due to the steric hindrance and the negative surface charge. Additionally, the hydrophobic effect of the biochar was also one of the adsorption mechanisms

The Aurora Kinase Inhibitor TAK901 Inhibits Glioblastoma Growth by Blocking SREBP1-Mediated Lipid Metabolism

Glioblastoma (GBM) is the most common and lethal malignant primary brain tumor. The standard treatment for GBM including surgical resection followed by radiation therapy and adjuvant chemotherapy with temozolomide remains unsatisfactory. In this study, we investigated the effects of the Aurora kinase inhibitor, TAK901, in GBM both in vitro and in vivo, and explored its key downstream targets. The effects of TAK901 were investigated using cell viability, cell apoptosis, live/dead, cell cycle, Transwell, 3D cell invasion, neuro-sphere, and self-renewal assays. Mechanistic studies were conducted using RNA-seq, lipid measurements, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blotting. The in vivo efficacy of TAK901 was validated using orthotopic xenograft GBM mouse models. In both GBM cells and GSCs, TAK901 remarkably reduced cell viability, self-renewal, migration and invasion and induced apoptosis and cell cycle arrest. Treatment with TAK901 considerably inhibited GBM growth in vivo. RNA-seq and RT-qPCR analyses showed that TAK901 downregulated the expression and activation of SREBP1. Moreover, SREBP1 overexpression alleviated the TAK901-mediated suppression of cell viability and apoptosis in GBM cells. Our results provide evidence that TAK901 inhibits GBM growth by suppressing SREBP1-mediated lipid metabolism

Biomimetic tri-layered small-diameter vascular grafts with decellularized extracellular matrix promoting vascular regeneration and inhibiting thrombosis with the salidroside

Small-diameter vascular grafts (SDVGs) are urgently required for clinical applications. Constructing vascular grafts mimicking the defining features of native arteries is a promising strategy. Here, we constructed a tri-layered vascular graft with a native artery decellularized extracellular matrix (dECM) mimicking the component of arteries. The porcine thoracic aorta was decellularized and milled into dECM powders from the differential layers. The intima and media dECM powders were blended with poly (L-lactide-co-caprolactone) (PLCL) as the inner and middle layers of electrospun vascular grafts, respectively. Pure PLCL was electrospun as a strengthening sheath for the outer layer. Salidroside was loaded into the inner layer of vascular grafts to inhibit thrombus formation. In vitro studies demonstrated that dECM provided a bioactive milieu for human umbilical vein endothelial cell (HUVEC) extension adhesion, proliferation, migration, and tube-forming. The in vivo studies showed that the addition of dECM could promote endothelialization, smooth muscle regeneration, and extracellular matrix deposition. The salidroside could inhibit thrombosis. Our study mimicked the component of the native artery and combined it with the advantages of synthetic polymer and dECM which provided a promising strategy for the design and construction of SDVGs