Cell-Selective Encapsulation within Metal-Organic Framework Shells via Precursor-Functionalized Aptamer Identification for Whole-Cell Cancer Vaccine.

Single-cell encapsulation is an emerging technology to endow cells with various functions, of which developing new applications in vivo is in high demand. Currently, metal-organic frameworks (MOFs) that are used as nanometric shells to coat living cells, however, have not realized cell-selective encapsulation. Here, a biocompatible and selective cell encapsulation strategy based on precursor-functionalized nucleolin aptamer and in situ MOF mineralization on the aptamer-identified cancer cell surface are developed. After MOF coating, the encapsulated cancer cells undergo immunogenic cell death, which is found associated with the changed cell stiffness (indicated by Young's modulus). The immunogenic dead cancer cells are used as whole-cell cancer vaccines (WCCVs), forming the integral WCCV-in-shell structure with enhanced immunogenicity ascribing from the surface-exposed calreticulin to promote dendritic cell recruitment, antigen presentation, and T-cell activation. The major activation pathways in the immune response are identified including tumor necrosis factor signaling pathway, cytokine-cytokine receptor interaction, and Toll-like receptor signaling pathway, suggesting the potential adjuvant effect of the MOF shells. After vaccination, WCCV-in-shell shows much better tumor immunoprophylaxis than either the imperfectly coated cancer cells or the traditional WCCV. This strategy is promising for the universal and facile development of novel whole-cell vaccines.

Recovery of microbial community in strongly alkaline bauxite residues after amending biomass residue.

The aim of this study was to characterize the effects of cornstalk biomass amendments on microbial communities in bauxite residues (BRs) by phylogenetic analysis. Improvements in soil geochemical, physical, and biological properties were assessed to identify the major factors controlling microbial community development in BRs. After one year of incubation, the salinity and structure of the amended BRs had gradually improved, with pH dropping from 11.39 to 9.89, the exchangeable sodium percentage (ESP) dropping from 86.3% to 35.2%, and the mean weight diameter (MWD) rising from 0.12 mm to 0.38 mm. Further analysis of community level physiological profiles (CLPP) showed that the microbial utilization of different carbohydrates had shifted significantly, in addition to increases in the diversity index H' (0.7-7.34), U (2.16-3.14), and the average well color development (0.059-1.08). Over the one-year outside incubation, the dominant fungal phyla in the BRs had shifted gradually from Ascomycota (85.64%) to Ascomycota (52.07%) and Basidiomycota (35.53%), while the dominant bacterial phyla had shifted from Actinobacteria (38.47%), Proteobacteria (21.39%), and Gemmatimonadetes (12.72%) to Actinobacteria (14.87%), Proteobacteria (23.53%), and Acidobacteria (14.37%). Despite these shifts, microbial diversity remained lower in the amended BRs than in the natural soil. Further redundancy analysis indicated that pH was the major factor driving shifts in the bacterial community, while aggregates were the major factor driving shifts in the fungal community. This study demonstrated that amendment with cornstalk biomass shifted the microbial community in the BRs from halophilic groups to acidogenic groups by improving the soil environmental conditions.

Resilience of fungal flora in bauxite residues amended with organic matter and vermiculite/fly ash.

The fungal community and soil geochemical, physical and biological parameters were analyzed, respectively, in bauxite residues (BRs) treated with organic matter and vermiculite/fly ash by phylogenetic analysis of ITS-18 S rRNA, community level physiological profiles (CLPP) and so on. The results indicated that after amendment of the BR, microbial utilization of carbohydrates and their enzyme activities were significantly increased, but fungal compositions at the phylum level were similar and dominated by the phylum of Ascomycota (82.05-98.96%, RA: relative abundance) after one year of incubation. The fungal taxa in the amended BR treatments, however, show significantly less alpha and beta diversity compared with the reference soils, although they still harbor a substantial novel taxon. The combined amendment of organic matter (OM) and vermiculite/fly ash significantly increases the fungal taxa at the genus and species level compared with solely OM amendment. The results of the following canonical correspondence analysis found that, over 90% variation of the fungal community could be explained by pH, OM and mean weight diameter (MWD) of aggregates; but the biological indicators, including urease (UR), dehydrogenase (DHA) and the value of average well color development (AWCD) could explain only 50% variation of the fungal flora in BRs. This paper indicated that resilience of fungal community in BRs was positively correlated with the BRs' improvement in fertility as well as biogeochemical properties, but alkalinity must be firstly decreased to the target level of BRs' rehabilitation.

Electrochemical assay for continuous monitoring of dynamic DNA methylation process.

A simple electrochemical strategy is reported for continuous monitoring of dynamic DNA methylation process over time. An electrochemical sensor was prepared by co-assembling of DNA probe and 6-mercapto-1-hexanol onto a gold electrode. The top of the DNA probe was labeled with 6-ferrocenylhexanethiol modified gold nanoparticle. The charge density between the C•G base pair was verified to be slightly reduced by DNA methylation, and could be further decelerated by ~ 25% upon co-locating a Br group onto methylated cytosine (mC). Therefore, in the presence of NaIO4/LiBr, the progressively methylated DNA on the sensor showed a clearly decreasing current over methylation time. The dynamic DNA methylation process was indicated continuously from the current decrease ratio, with a limit of detection of 0.0372µM. The strategy is convenient, cost-effective, and enable continuous profiling methylation process without distortion. Besides, the strategy was successfully applied for the studies on inhibitor screening and flanking sequence preference of DNA methyltransferase 3a. The results show that the activity of DNA methyltransferase 3a can be mildly inhibited by epigallocatechin gallate, and varies towards different flanking sequence with an order of 5'-CCGG-3' < 5'-CGCG-3' < 5'-CGCA-3'.

Preparation and characterization of acorn starch/poly(lactic acid) composites modified with functionalized vegetable oil derivates.

Composites of acorn starch (AS) and poly(1actic acid) (PLA) modified with dimer fatty acid (DFA) or dimer fatty acid polyamide (DFAPA) were produced by a hot-melt extrusion method. The effects of DFA and DFAPA contents on the mechanical, hydrophobic, thermal properties and melt fluidity of the composites were studied under an invariable AS-to-PLA mass ratio of 40/60. SEM and DMA research results show that the compatibility of AS/PLA composites are determined by the dosage of DFA or DFAPA. The hydrophobicity and melt fluidity of composites are improved with the addition of DFA and DFAPA. The glass transition temperatures of the composites are all reduced remarkably by additives DFA and DFAPA. However, DFA and DFAPA exert different effects on the mechanical properties of AS/PLA composites. In the DFAPA-modified system, the tensile and flexural strength first increase and then decrease with the increase of DFAPA dosage; the mechanical strength is maximized when the dosage of DFAPA is 2 wt% of total weight. In the DFA-modified system, the tensile and flexural strength decrease with the increase of DFA dosage.