Vaccination with HIV/SIV DNAs elicits potent T-cell responses. To improve humoral immune responses, we combined DNA and protein in a co-immunization protocol using in vivo electroporation in mice and macaques. DNA&protein co-immunization induced higher antibody responses than DNA or protein alone, or DNA prime/protein boost in mice. DNA&protein co-immunization induced similar levels of cellular responses as those obtained by DNA only vaccination. The inclusion of SIV or HIV Env gp120 protein did not impair the development of cellular immune responses elicited by DNA present in the vaccine regimen. In macaques, the DNA&protein co-immunization regimen also elicited higher levels of humoral responses with broader cross-neutralizing activity. Despite the improved immunogenicity of DNA&protein co-immunization, the protein formulation with the EM-005 (GLA-SE) adjuvant further increased the anti-Env humoral responses. Dissecting the contribution of EM-005, we found that its administration upregulated the expression of co-stimulatory molecules and stimulated cytokine production, especially IL-6, by dendritic cells in vivo. These terminally differentiated, mature, dendritic cells possibly promote higher levels of humoral responses, supporting the inclusion of the EM-005 adjuvant with the vaccine. Thus, DNA&protein co-immunization is a promising strategy to improve the rapidity of development, magnitude and potency of the humoral immune responses.
Most microwave absorbers lose their function under harsh working conditions, such as a high temperature and an oxidative environment. Here, we developed a heterogeneous ZrN 0.4 B 0.6 /SiC nanohybrid via combined catalytic chemical vapor deposition (CCVD) and chemical vapor infiltration (CVI) processes using ZrB 2 as the starting material. The composition and structure of the ZrN 0.4 B 0.6 /SiC nanohybrid were controlled by tuning the CCVD and CVI parameters, such as reaction temperature, time, and reactant concentration. The optimal heterogeneous ZrN 0.4 B 0.6 /SiC nanohybrids were obtained initially by preparing ZrB 2 @C via the CCVD process at 650 °C for 30 min and the subsequent CVI at 1500 °C, where the ZrB 2 @C reacted with Si under N 2 . The ZrN 0.4 B 0.6 /SiC nanohybrid exhibited enhanced microwave absorption ability with a minimum reflection loss value of approximately −50.8 dB at 7.7 GHz, a thickness of ∼3.05 mm, and antioxidation features at a high temperature of 600 °C. The heterogeneous ZrN 0.4 B 0.6 /SiC nanohybrid possessed reasonable conductivity, leading to dielectric loss, whereas SiC nanofibers formed a three-dimensional network that brought higher dipole moments, whereas a small part of the ZrN 0.4 B 0.6 /SiC nanohybrid structure generated an effective interface for higher attenuation of microwaves. Therefore, these material features synergistically resulted in a well-defined Debye relaxation, Maxwell−Wagner relaxation, dipole polarization, and the quarter-wavelength cancellation, which accounted for the enhanced microwave absorption.
Descurainia sophia is one of the most notorious broadleaf weeds in China and has evolved extremely high resistance to acetolactate synthase (ALS)-inhibiting herbicide tribenuron-methyl. The target-site resistance due to ALS gene mutations was well-known, while the non-target-site resistance is not yet well-characterized. Metabolic resistance, which is conferred by enhanced rates of herbicide metabolism, is the most important NTSR. To explore the mechanism of metabolic resistance underlying resistant (R) D. sophia plants, tribenuron-methyl uptake and metabolism levels, qPCR reference gene stability, and candidate P450 genes expression patterns were investigated. The results of liquid chromatography-mass spectrometry (LC-MS) analysis indicated that the metabolic rates of tribenuron-methyl in R plants was significantly faster than in susceptible (S) plants, and this metabolism differences can be eliminated by P450 inhibitor malathion. The genes for 18S rRNA and TIP41-like were identified as the most suitable reference genes using programs of BestKeeper, NormFinder, and geNorm. The P450 gene CYP96A146 constitutively overexpressed in R plants compared to S plants; this overexpression in R plants can be suppressed by malathion. Taken together, a higher expression level of P450 genes, leading to higher tribenuron-methyl metabolism, appears to be responsible for metabolic resistance to tribenuron-methyl in R D. sophia plants.
Fucoidan, the complex fucose-containing sulphated polysaccharide varies considerably in structure, composition, and bioactivity, depending on the source, species, seasonality, and extraction method. In this study, we examined five fucoidans extracted from the same seaweed species Undaria pinnatifida but from different geological locations, and compared them to the laboratory-grade fucoidan from Sigma (S). The five products differed in molecular composition. The amount of over 2 kDa low molecular weight fraction (LMWF) of the New Zealand crude fucoidan (S1) was larger than that of S, and this fraction was unique, compared to the other four fucoidans. The difference of molecular compositions between S and S1 explained our previous observation that S1 exhibited different anticancer profile in some cancer cell lines, compared with S. Since we observed this unique LMWF, we compared the cytotoxic effects of a LMWF and a high molecular weight fucoidan (HMWF) in two breast cancer cell lines—MCF-7 and MDA-MB-231. Results indicated that the molecular weight is a critical factor in determining the anti-cancer potential of fucoidan, from the New Zealand U. pinnatifida, as the LMWF exhibited a dose-dependent inhibition on the proliferation of breast cancer cells, significantly better than the HMWF, in both cell lines. A time-dependent inhibition was only observed in the MCF-7. Induction of caspase-dependent apoptosis was observed in the MDA-MB-231 cells, through the intrinsic apoptosis pathway alone, or with the extrinsic pathway. LMWF stimulated a dose-dependent NOS activation in the MDA-MB-231 cells. In conclusion, the fucoidan extracted from the New Zealand U. pinnatifida contains a unique LMWF, which could effectively inhibit the growth of breast cancer cell lines. Therefore, the LMWF from New Zealand U. pinnatifida could be used as a supplement cancer treatment.
Developing highly efficient magnetic microwave absorbers (MAs) is crucial, and yet challenging for anti-corrosion properties in extremely humid and salt-induced foggy environments. Herein, a dual-oxide shell of ZnO/Al2O3 as a robust barrier to FeSiAl core is introduced to mitigate corrosion resistance. The FeSiAl@ZnO@Al2O3 layer by layer hybrid structure is realized with atomic-scale precision through the atomic layer deposition technique. Owing to the unique hybrid structure, the FeSiAl@ZnO@Al2O3 exhibits record-high microwave absorbing performance in low-frequency bands covering L and S bands with a minimum reflection loss (RLmin) of -50.6 dB at 3.4 GHz. Compared with pure FeSiAl (RLmin of -13.5 dB, a bandwidth of 0.5 GHz), the RLmin value and effective bandwidth of this designed novel absorber increased up to ~ 3.7 and ~ 3 times, respectively. Furthermore, the inert ceramic dual-shells have improved 9.0 times the anti-corrosion property of FeSiAl core by multistage barriers towards corrosive medium and obstruction of the electric circuit. This is attributed to the large charge transfer resistance, increased impedance modulus |Z|0.01 Hz, and frequency time constant of FeSiAl@ZnO@Al2O3. The research demonstrates a promising platform toward the design of next-generation MAs with improved anti-corrosion properties.
Aspect extraction relies on identifying aspects by discovering coherence among words, which is challenging when word meanings are diversified and processing on short texts. To enhance the performance on aspect extraction, leveraging lexical semantic resources is a possible solution to such challenge. In this paper, we present an unsupervised neural framework that leverages sememes to enhance lexical semantics. The overall framework is analogous to an autoenoder which reconstructs sentence representations and learns aspects by latent variables. Two models that form sentence representations are proposed by exploiting sememes via (1) a hierarchical attention; (2) a context-enhanced attention. Experiments on two real-world datasets demonstrate the validity and the effectiveness of our models, which significantly outperforms existing baselines.
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