A promising strategy to improve the stability and immunogenicity of killed but metabolically active vaccines: low-temperature preparation and coating of nanoparticles.

Bacteria are becoming an increasingly serious threat to human health. The emergence of super bacteria makes clinical treatment more difficult. Vaccines are one of the most effective means of preventing and treating bacterial infections. As a new class of vaccines, killed but metabolically active (KBMA) vaccines provide the immunogenicity of live vaccines and the safety of inactivated vaccines. Herein, a promising strategy is proposed to improve the stability and immunogenicity of KBMA vaccines. KBMA vaccines were produced at low temperature (4 °C), and the bacterial surface was engineered using mesoporous silica nanoparticle (MSN) coating. Compared to vaccines prepared at room temperature, the metabolic activity of KBMA vaccines prepared at 4 °C remarkably improved. Benefiting from the induction of MSNs, the stability of KBMA vaccines was increased and the preservation time was prolonged at 4 °C. Meanwhile, metabolomics analysis showed that the metabolite spectrum of live bacteria changed after photochemical treatment and MSN coating, which interfered with organic acid metabolism pathways, lipid metabolism and biosynthesis of secondary metabolites. Furthermore, the immune response in the mice treated with KBMA/MSN vaccines was similar to that in those treated with live vaccines and stronger than that in those treated with inactivated vaccines. In comparison with the control group, bacteria tissue burdens of KBMA/MSN group were significantly reduced. CD4+ T cells dominated immune responses for the protection of mice. Thus, the current work promotes the application of KBMA vaccines, providing an alternative choice for treating bacterial infections.

Identification of immune- and oxidative stress-related signature genes as potential targets for mRNA vaccines for pancreatic cancer patients.

Adenocarcinoma of the pancreas (PAAD) is one of the deadliest malignant tumors, and messenger ribonucleic acid vaccines, which constitute the latest generation of vaccine technology, are expected to lead to new ideas for the treatment of pancreatic cancer. The Cancer Genome Atlas-PAAD and Genotype-Tissue Expression data were merged and analyzed. Weighted gene coexpression network analysis was used to identify gene modules associated with tumor mutational burden among the genes related to both immunity and oxidative stress. Differentially expressed immune-related oxidative stress genes were screened via univariate Cox regression analysis, and these genes were analyzed via nonnegative matrix factorization. After immune infiltration analysis, least absolute shrinkage and selection operator regression combined with Cox regression was used to construct the model, and the usefulness of the model was predicted based on the receiver operating characteristic curve and decision curve analysis curves after model construction. Finally, metabolic pathway enrichment was analyzed using gene set enrichment analysis combined with Kyoto Encyclopedia of Genes and Genomes and gene ontology biological process analyses. This model consisting of the ERAP2, mesenchymal-epithelial transition factor (MET), CXCL9, and angiotensinogen (AGT) genes can be used to help predict the prognosis of pancreatic cancer patients more accurately than existing models. ERAP2 is involved in immune activation and is important in cancer immune evasion. MET binds to hepatocyte growth factor, leading to the dimerization and phosphorylation of c-MET. This activates various signaling pathways, including MAPK and PI3K, to regulate the proliferation, invasion, and migration of cancer cells. CXCL9 overexpression is associated with a poor patient prognosis and reduces the number of CD8 + cytotoxic T lymphocytes in the PAAD tumor microenvironment. AGT is cleaved by the renin enzyme to produce angiotensin 1, and AGT-converting enzyme cleaves angiotensin 1 to produce angiotensin 2. Exposure to AGT-converting enzyme inhibitors after pancreatic cancer diagnosis is associated with improved survival. The 4 genes identified in the present study - ERAP2, MET, CXCL9, and AGT - are expected to serve as targets for messenger ribonucleic acid vaccine development and need to be further investigated in depth.

[Dynamic changes of soil amino sugar contents under drying and wetting cycle].

A soil incubation test was conducted to study the quantitative changes of three amino sugars (glucosamine, muramic acid, and galactosamine) derived from microbes under drying and wetting cycle, and to analyze the relative contribution of soil bacteria and fungi to the turnover of soil organic matter by using the measured glucosamine/muramic acid ratio. Under continuous wetting, the degradation of bacteria-derived muramic acid was faster than that of fungi-derived glucosamine, and the degradation rate of galactosamine was the lowest. Drying and wetting cycle altered the degradation characteristics of the three amino sugars. As compared with that under continuous wetting, the degradation rate of bacteria-derived muramic acid at the prophase of drying and wetting was faster than that of fungi-derived glucosamine, and, with the increasing frequency of drying and wetting cycle, the degradation rate of fungi-derived glucosamine was faster than that of bacteria-derived muramic acid. These results indicated that drying and wetting cycle changed the course of the microbial transformation of soil amino sugar-derived nitrogen.