We know a great deal about the biochemistry of cells because they can be isolated and studied. The biochemistry of the much more complex in vivo environment is more difficult to study because the only ways to quantitate concentrations is to sacrifice the animal or biopsy the tissue. Either method disrupts the environment profoundly and neither method allows longitudinal studies on the same individual. Methods of measuring chemical concentrations in vivo are very valuable alternatives to sacrificing groups of animals. We are developing microscopic magnetic nanoparticle (mNP) probes to measure the concentration of a selected molecule in vivo. The mNPs are targeted to bind the selected molecule and the resulting reduction in rotational freedom can be quantified remotely using magnetic spectroscopy. The mNPs must be contained in micrometer sized porous shells to keep them from migrating and to protect them from clearance by the immune system. There are two key issues in the development of the probes. First, we demonstrate the ability to measure concentrations in the porous walled alginate probes both in phosphate buffered saline and in blood, which is an excellent surrogate for the complex and challenging in vivo environment. Second, sensitivity is critical because it allows microscopic probes to measure very small concentrations very far away. We report sensitivity measurements on recently introduced technology that has allowed us to improve the sensitivity by two orders of magnitude, a factor of 200 so far.

Microbial interactions played crucial roles in influencing the assembly, stability, and function of the microbial community. The metabolites of pit mud microbiota are the key to flavor formation of Chinese strong-flavor baijiu.

Purpose: Malignant melanoma (MM), the most lethal skin cancer, is highly invasive and metastatic. These qualities are related to not only genetic mutations in MM itself but also the interaction of MM cells with the immune system and microenvironment. This study aimed to construct a combined immunotherapy and gene therapy drug delivery system for the effective treatment of MM. Methods: Mature dendritic cell (mDC) exosomes (mDexos) with immune induction functions were used as carriers. BRAF siRNA (siBRAF) with the ability to silence mutated BRAF in MM was encapsulated in mDexos by electroporation to construct a biomimetic nanosystem for the codelivery of immunotherapy and gene therapy drugs (siBRAF-mDexos) to the MM microenvironment. Then, we investigated the nanosystem’s serum stability and biocompatibility, uptake efficiency in mouse melanoma cells (B16-F10 cells), cytotoxicity against B16-F10 cells and inhibitory effect on BRAF expression. Furthermore, we evaluated its antimelanoma activity and safety in vivo. Results: SiBRAF-mDexos were nanosized. Compared to siBRAF, siBRAF-mDexos displayed significantly increased serum stability, biocompatibility, uptake efficiency in B16-F10 cells, and cytotoxicity to B16-F10 melanoma cells; they also had a significantly greater inhibitory effect on BRAF expression and induced T-lymphocyte proliferation. Moreover, compared with siBRAF, siBRAF-mDexos showed significantly enhanced anti-MM activity and a high level of safety in vivo. Conclusion: The study suggests that the siBRAF-mDexo biomimetic drug codelivery system can be used to effectively treat MM, which provides a new strategy for combined gene therapy and immunotherapy for MM.

Background: Increasing studies suggest that the microbiome-gut-brain axis plays a fundamental role in developing autism spectrum disorder (ASD). Objectives: We aimed to explore biomarkers from gut bacteria in ASD and the dietary vitamin A (VitA) relationship with intestinal bacteria of autistic children and provide a theoretical basis for dietary regulation of ASD. Methods: Ten autistic children aged 2 to 6 from special training facilities were enrolled from 2017 to 2018. At the same time, 10 healthy children aged 2 to 6 from a kindergarten were collected as a control. All participants were from Chongqing, China. The 16sRNA amplicon sequencing was used to analyze children's intestinal bacteria. The serum retinol level was detected by high-performance liquid chromatography (HPLC), and children's dietary intake was analyzed using three-day 24-hour dietary recalls. Results: There were significant differences in alpha diversity between the groups. Also, a higher relative abundance of Prevotellaceae, Prevotella 9, and Roseburia was observed among ASD children. We also found decreases in 9 bacteria (Enterobacteriales, Gammaproteobacteria, Enterobacteriaceae, Clostridiaceae 1, Clostridium sensu stricto 1, Escherichia-Shigella, Bacteroides fragilis, Escherichia coli, and Clostridium neonatale). Dietary VitA intake and serum retinol concentration were lower in the ASD group than in the control group. Meanwhile, serum VitA had a significantly negative correlation with the abundance of intestinal Prevotella 9. Conclusions: Our study helps identify some bacterial biomarkers for ASD, as in previous reports. Meanwhile, the study suggests that dietary VitA may be involved in the clinical symptoms of ASD by regulating the intestinal bacteria Prevotella. It may provide a new way to treat ASD in the future. Further studies are needed to identify the results by expanding the sample size and developing animal experiments.