Self-adjuvant Astragalus polysaccharide-based nanovaccines for enhanced tumor immunotherapy: a novel delivery system candidate for tumor vaccines.

The study of tumor nanovaccines (NVs) has gained interest because they specifically recognize and eliminate tumor cells. However, the poor recognition and internalization by dendritic cells (DCs) and insufficient immunogenicity restricted the vaccine efficacy. Herein, we extracted two molecular-weight Astragalus polysaccharides (APS, 12.19 kD; APSHMw, 135.67 kD) from Radix Astragali and made them self-assemble with OVA257-264 directly forming OVA/APS integrated nanocomplexes through the microfluidic method. The nanocomplexes were wrapped with a sheddable calcium phosphate layer to improve stability. APS in the formed nanocomplexes served as drug carriers and immune adjuvants for potent tumor immunotherapy. The optimal APS-NVs were approximately 160 nm with uniform size distribution and could remain stable in physiological saline solution. The FITC-OVA in APS-NVs could be effectively taken up by DCs, and APS-NVs could stimulate the maturation of DCs, improving the antigen cross-presentation efficiency in vitro. The possible mechanism was that APS can induce DC activation via multiple receptors such as dectin-1 and Toll-like receptors 2 and 4. Enhanced accumulation of APS-NVs both in draining and distal lymph nodes were observed following s.c. injection. Smaller APS-NVs could easily access the lymph nodes. Furthermore, APS-NVs could markedly promote antigen delivery efficiency to DCs and activate cytotoxic T cells. In addition, APS-NVs achieve a better antitumor effect in established B16-OVA melanoma tumors compared with the OVA+Alum treatment group. The antitumor mechanism correlated with the increase in cytotoxic T cells in the tumor region. Subsequently, the poor tumor inhibitory effect of APS-NVs on the nude mouse model of melanoma also confirmed the participation of antitumor adaptive immune response induced by NVs. Therefore, this study developed a promising APS-based tumor NV that is an efficient tumor immunotherapy without systemic side effects.

Isolation, Purification, and Structural Characterization of Polysaccharides from Codonopsis pilosula and Their Anti-Tumor Bioactivity by Immunomodulation.

The activity of polysaccharides is usually related to molecular weight. The molecular weight of polysaccharides is critical to their immunological effect in cancer therapy. Herein, the Codonopsis polysaccharides of different molecular weights were isolated using ultrafiltration membranes of 60- and 100-wDa molecular weight cut-off to determine the relationship between molecular weight and antitumor activities. First, three water-soluble polysaccharides CPPS-I (<60 wDa), CPPS-II (60-100 wDa), and CPPS-III (>100 wDa) from Codonopsis were isolated and purified using a combination of macroporous adsorption resin chromatography and ultrafiltration. Their structural characteristics were determined through chemical derivatization, GPC, HPLC, FT-IR, and NMR techniques. In vitro experiments indicated that all Codonopsis polysaccharides exhibited significant antitumor activities, with the tumor inhibition rate in the following order: CPPS-II > CPPS-I > CPPS-III. The treatment of CPPS-II exhibited the highest inhibition rate at a high concentration among all groups, which was almost as efficient as that of the DOX·HCL (10 µg/mL) group at 125 µg/mL concentration. Notably, CPPS-II demonstrated the ability to enhance NO secretion and the antitumor ability of macrophages relative to the other two groups of polysaccharides. Finally, in vivo experiments revealed that CPPS-II increased the M1/M2 ratio in immune system regulation and that the tumor inhibition effect of CPPS-II + DOX was superior to that of DOX monotherapy, implying that CPPS-II + DOX played a synergistic role in regulating the immune system function and the direct tumor-killing ability of DOX. Therefore, CPPS-II is expected to be applied as an effective cancer treatment or adjuvant therapy.

Rhodiola rosea polysaccharides-based nanoparticles loaded with DOX boosts chemo-immunotherapy for triple-negative breast cancer by re-educating Tumor-associated macrophages.

Hydrophobic drug delivery vectors suffer significant challenges in cancer therapy, including efficient encapsulation and tumor targeting ability. In the present study, Rhodiola rosea polysaccharides (RHPs), which have the ability to modulate Tumor-associated macrophages and typical structural characteristics, were employed as an immunoactive vector for drug delivery. Folic acid (FA) and stearic acid (SA) were chemically modified to the backbone of RHPs to obtain the self-assembly and tumor-targeting behavior. Further, the hydrophobic drug, doxorubicin (DOX), was encapsulated in the RHPs derivatives (FA-RHPs-SA) with high efficiency. Additionally, the optimally formed DOX@FA-RHPs-SA had a uniform size distribution of approximately 196 nm and a pH-sensitive release capacity in different acidic conditions. In vitro experiments demonstrated that tumor cells could efficiently uptake DOX@FA-RHPs-SA. Furthermore, the modulatory function of the FA-RHPs-SA on RAW264.7 macrophages was also demonstrated in the transition from M0 to M1 phenotypes, and the M2 differentiated into the M1. Finally, the in vivo antitumor study revealed that the inhibitory effect of DOX@FA-RHPs-SA was superior to the DOX monotherapy treatment, and the new preparation functioned synergistically by inducing tumor cell apoptosis and modulating immune cell function. In conclusion, this study described an RHPs-based hydrophobic delivery vector and achieved an additional helpful antitumor effect by modulating Tumor-associated macrophages.

Testing the impact of first-mover advantage on household energy-related carbon emissions: an exploratory study from six urban agglomerations in China.

The household sector has become the second-largest source of energy consumption and CO2 emissions in China. It is important to understand the trends and changing mechanisms of household energy-related CO2 emissions (HECEs) in different social stages for mitigating the impact of climate change. However, the existing trends in HECEs and whether they are congruent with the expectation that HECEs in later developed areas are lower than those in priority areas under the same economic level are unclear. Here, we compared the per capita HECEs (PHECEs) of urban agglomerations under the same economic standards and analyzed the causes of the comparative results. We find that (1) HECEs increased rapidly from 3.65 × 108 t to 12.42 × 108 t during 1995-2017, with an average annual growth rate of 14.19%; (2) urban agglomerations that developed earlier do not have higher PHECEs. The PHECEs of urban agglomerations with moderate and later development do not decrease under increased social, technological, and cognitive conditions; (3) carbon intensity (CI), energy intensity (EI), and per capita regional gross domestic product (PCG) have a positive impact on PHECEs, and the potential impact of EI on PHECEs reduction is greater; (4) the effects of CI, EI, and PCG on PHECEs in different urban agglomerations are various. However, these effects are similar within urban agglomerations. Our study provides a reference for reducing CO2 emissions in the household sector and for the green development of urban agglomerations and emphasizes that the growth of HECE at a reasonable level is necessary when technology does not meet sufficient constraints.

Physicochemical properties and greenhouse gas emissions of water body during the decomposition of Potamogeton crispus with different values of initial debris biomass.

A sediment-water mesocosm experiment was set up to identify the effects of different debris biomass P. crispus decomposition on water body physicochemical properties and greenhouse gas emissions in Dongping Lake, a typical shallow macrophytic lake in the north of China. The results indicated that the decomposition of high biomass (BL-2) of P. crispus could significantly affect the physicochemical properties of water bodies, especially within the first 47 days. During the experiment, DO and water pH in BL-2 were significantly lower, while NH3-N, NO2--N, DOC, and DRP in surface water and OM in sediment were significantly higher than those in the low biomass treatment (BL-1) and zero control (CK). Moreover, the DOC in BL-1 were significantly higher than CK. The decomposition of P. crispus significantly affected the emission fluxes of CH4 and CO2, but had no significant impact on N2O emission. CH4 and CO2 fluxes were generally more significantly correlated with the properties of surface water in BL-2 than in BL-1. High debris biomass decomposition significantly promoted the emission of CH4 enhancing the source effect of water body, while the decomposition of both low and high biomass notably promoted the emission of CO2 converting the water bodies from sink to source of CO2. There were significant differences in global warming potential among the three groups in which CH4 contributed most. Considering the negative impact on water environment and elevated carbon emission during the decomposition of P. crispus, it was suggested to strengthen the management of P. crispus in Dongping Lake.

Biological denitrification in a macrophytic lake: implications for macrophytes-dominated lake management in the north of China.

Denitrification plays an important role in nitrogen (N) removal in freshwater ecosystems. Aquatic plants might have an impact on the sediment denitrification of water body, especially in macrophytes-dominated lake; however, there were different opinions about it. Our hypothesis was that the sediment denitrification rates differ significantly in different vegetation zones and seasons because of direct and indirect effect of the aquatic plants. Therefore, we studied sediment denitrification in Dongping Lake, a typical macrophytes-dominated lake located in the north of China. The acetylene inhibition technique was used to quantify the sediment denitrification rates (DRs) in the Phragmites communis (P. communis) zone, aquaculture zone, Potamogeton crispus (P. crispus) zone and mixed vegetation zone in July (summer), October (autumn), December (winter) of 2015 and March (spring) of 2016. The results showed that the average DRs were significantly higher in the P. communis zone (69.0 ± 91.6 µmol N m-2 h-1) than the mixed vegetation zone (8.70 ± 5.44 µmol N m-2 h-1), and the average DRs represented significant seasonal difference as in the order of winter (74.5 ± 88.3 µmol N m-2 h-1) > autumn (15.7 ± 18.6 µmol N m-2 h-1) ≈ summer (10.7 ± 5.90 µmol N m-2 h-1) > spring (3.85 ± 1.29 µmol N m-2 h-1). The DRs generally decreased with the increasing of depth; however, significant increase of DRs with depth were found in certain seasons at the vegetated zones except the non-vegetated zone (the aquaculture zone) indicating the possible rhizosphere effect of aquatic plants on denitrification. The higher DRs and cycling rates of nitrate in the P. communis zone might be related to the larger biomass and oxygen transporting capacity of P. communis than those of the other aquatic plants. Winter peaks of DRs might be attributed to the higher NO3- load and the absence of the plant uptake. The high cycling rates of nitrate in Dongping Lake indicated an enhanced internal N cycling by aquatic plants. Sediment denitrification could remove about 537.7 t N every year, which was about 26.5% of annual TN loading in Dongping Lake.