Ligang Deng

. Trace elements, especially toxic trace elements, were present at very low concentrations; however, Pb concentrations in cow milk reached the MRLs established by the Codex Alimentarius Commission. Data were analyzed by chemometrics to evaluate the correlations between elements in the milk samples. PCA and factor analysis highlighted the relationship between element distribution and milk type. The LDA model correctly identified most milk types. Element analysis combined with chemometrics can be used to distinguish milk types.

BACKGROUND: Neoantigen (NeoAg) peptides displayed at the tumor cell surface by human leukocyte antigen molecules show exquisite tumor specificity and can elicit T cell mediated tumor rejection. However, few NeoAgs are predicted to be shared between patients, and none to date have demonstrated therapeutic value in the context of vaccination. METHODS: We report here a phase I trial of personalized NeoAg peptide vaccination (PPV) of 24 stage III/IV non-small cell lung cancer (NSCLC) patients who had previously progressed following multiple conventional therapies, including surgery, radiation, chemotherapy, and tyrosine kinase inhibitors (TKIs). Primary endpoints of the trial evaluated feasibility, tolerability, and safety of the personalized vaccination approach, and secondary trial endpoints assessed tumor-specific immune reactivity and clinical responses. Of the 16 patients with epidermal growth factor receptor (EGFR) mutations, nine continued TKI therapy concurrent with PPV and seven patients received PPV alone. RESULTS: Out of 29 patients enrolled in the trial, 24 were immunized with personalized NeoAg peptides. Aside from transient rash, fatigue and/or fever observed in three patients, no other treatment-related adverse events were observed. Median progression-free survival and overall survival of the 24 vaccinated patients were 6.0 and 8.9 months, respectively. Within 3-4 months following initiation of PPV, seven RECIST-based objective clinical responses including one complete response were observed. Notably, all seven clinical responders had EGFR-mutated tumors, including four patients that had continued TKI therapy concurrently with PPV. Immune monitoring showed that five of the seven responding patients demonstrated vaccine-induced T cell responses against EGFR NeoAg peptides. Furthermore, two highly shared EGFR mutations (L858R and T790M) were shown to be immunogenic in four of the responding patients, all of whom demonstrated increases in peripheral blood neoantigen-specific CD8+ T cell frequencies during the course of PPV. CONCLUSIONS: These results show that personalized NeoAg vaccination is feasible and safe for advanced-stage NSCLC patients. The clinical and immune responses observed following PPV suggest that EGFR mutations constitute shared, immunogenic neoantigens with promising immunotherapeutic potential for large subsets of NSCLC patients. Furthermore, PPV with concurrent EGFR inhibitor therapy was well tolerated and may have contributed to the induction of PPV-induced T cell responses.

Inflammation and oxidative stress play key roles in the process of aging and age-related diseases. Since serine availability plays important roles in the support of antioxidant and anti-inflammatory defense system, we explored whether serine deficiency affects inflammatory and oxidative status in D-galactose-induced aging mice. Male mice were randomly assigned into four groups: mice fed a basal diet, mice fed a serine- and glycine-deficient (SGD) diet, mice injected with D-galactose and fed a basal diet, and mice injected with D-galactose and fed an SGD diet. The results showed that D-galactose resulted in oxidative and inflammatory responses, while serine deficiency alone showed no such effects. However, serine deficiency significantly exacerbated oxidative stress and inflammation in D-galactose-treated mice. The composition of fecal microbiota was affected by D-galactose injection, which was characterized by decreased microbiota diversity and downregulated ratio of Firmicutes / Bacteroidetes , as well as decreased proportion of Clostridium XIVa . Furthermore, serine deficiency exacerbated these changes. Additionally, serine deficiency in combination with D-galactose injection significantly decreased fecal butyric acid content and gene expression of short-chain fatty acid transporters ( Slc16a3 and Slc16a7 ) and receptor ( Gpr109a ) in the brain. Finally, serine deficiency exacerbated the decrease of expression of phosphorylated AMPK and the increase of expression of phosphorylated NF κ B p65, which were caused by D-galactose injection. In conclusion, our results suggested that serine deficiency exacerbated inflammation and oxidative stress in D-galactose-induced aging mice. The involved mechanisms might be partially attributed to the changes in the microbiota-gut-brain axis affected by serine deficiency.