Altered epitopes enhance macrophage-mediated anti-tumour immunity to low-immunogenic tumour mutations.

Personalized neoantigen therapy has shown long-term and stable efficacy in specific patient populations. However, not all patients have sufficient levels of neoantigens for treatment. Although somatic mutations are commonly found in tumours, a significant portion of these mutations do not trigger an immune response. Patients with low mutation burdens continue to exhibit unresponsiveness to this treatment. We propose a design paradigm for neoantigen vaccines by utilizing the highly immunogenic unnatural amino acid p-nitrophenylalanine (pNO2Phe) for sequence alteration of somatic mutations that failed to generate neoepitopes. This enhances the immunogenicity of the mutations and transforms it into a suitable candidate for immunotherapy. The nitrated altered epitope vaccines designed according to this paradigm is capable of activating circulating CD8+ T cells and inducing immune cross-reactivity against autologous mutated epitopes in different MHC backgrounds (H-2Kb, H-2Kd, and human HLA-A02:01), leading to the elimination of tumour cells carrying the mutation. After immunization with the altered epitopes, tumour growth was significantly inhibited. It is noteworthy that nitrated epitopes induce tumour-infiltrating macrophages to differentiate into the M1 phenotype, surprisingly enhancing the MHC II molecule presenting pathway of macrophages. Nitrated epitope-treated macrophages have the potential to cross-activate CD4+ and CD8+ T cells, which may explain why pNO2Phe can enhance the immunogenicity of epitopes. Meanwhile, the immunosuppressive microenvironment of the tumour is altered due to the activation of macrophages. The nitrated neoantigen vaccine strategy enables the design of vaccines targeting non-immunogenic tumour mutations, expanding the pool of potential peptides for personalized and shared novel antigen therapy. This approach provides treatment opportunities for patients previously ineligible for new antigen vaccine therapy.

Co-metabolism of Na+/K+ ion regulated physiological enhancement on selenium-accumulation in Saccharomyces yeasts.

BACKGROUND: Selenium is an important nutritional supplement that mainly exists naturally in soil as inorganic selenium. Saccharomyces cerevisiae cells are excellent medium for converting inorganic selenium in nature into organic selenium. RESULTS: Under the co-stimulation of sodium selenite (Na2SeO3) and potassium selenite (K2SeO3), the activity of selenophosphate synthetase (SPS) was improved up to about five folds more than conventional Na2SeO3 group with the total selenite salts content of 30 mg/L. Transcriptome analysis first revealed that due to the sharing pathway between sodium ion (Na+) and potassium ion (K+), the K+ largely regulates the metabolisms of amino acid and glutathione under the accumulation of selenite salt. Furthermore, K+ could improve the tolerance performance and selenium-biotransformation yields of Saccharomyces cerevisiae cells under Na2SeO3 salt stimulation. CONCLUSION: The important role of K+ in regulating the intracellular selenium accumulation especially in terms of amino acid metabolism and glutathione, suggested a new direction for the development of selenium-enrichment supplements with Saccharomyces cerevisiae cell factory. © 2024 Society of Chemical Industry.

Sensitive and reproducible gold nanostar@metal-organic framework-based SERS membranes for the online monitoring of the freshness of shrimps.

Given the prevalence of food safety, online monitoring of food quality is essential. Surface-enhanced Raman scattering (SERS) has excellent sensitivity and molecular fingerprinting capabilities in analytical fields, but its accuracy in food safety monitoring is severely constrained, particularly for gaseous molecules. To further develop the SERS technique in food sensing, in this work, a slippery liquid-infused porous surface (SLIPS) platform was developed for the real-time monitoring of the change in gaseous molecules in shrimp spoilage processes. In order to monitor the change in pH and gaseous biogenic amine molecules (BAs), 4-mercaptopyridine (4-Mpy) and 4-mercaptobenzaldehyde (4-MBA)-functionalized ZIF-8-encapsulated gold nanostars (AuNS@ZIF-8) were utilized as response probes, respectively. Due to the superior gaseous molecule trapping ability of ZIF-8 and the excellent enrichment effect of SLIPS substrates, the use of 4-Mpy and 4-MBA-functionalized AuNS@ZIF-8-SLIPS substrates exhibited excellent online SERS sensing performance for pH and gaseous putrescine molecules. The detection ranges for pH and gaseous BAs were 4.0-9.0 and 10-7-10-3 (v/v) with RSDs of 4.1% and 4.2%, respectively. Furthermore, the SERS monitoring platform was used to monitor shrimp spoilage at 25 °C and 4 °C in real time. Hence, the AuNS@ZIF-8-SLIPS membrane strategy can serve as a promising alternative to ensure accurate, real-time, and non-destructive monitoring of gaseous molecules for food freshness.

Surface amorphous coating for an economical and high-stability current collector for rechargeable aluminum-ion batteries.

Rechargeable aluminum-ion batteries (AIBs) are regarded as the next-generation energy storage devices due to their low flammability, low cost and high power density as well as abundant aluminum (Al) reserves. However, these popular ionic liquid electrolytes contain highly corrosive acid, which always corrodes the most used positive current collector, thus hindering the commercialization of AIBs. This study proposes an efficient and economical method of coating amorphous Ni3S2compound on a nickel metal current collector (Ni-S/Ni). The conductivity and the onset oxidation potential of amorphous Ni3S2coating can be up to 2.3 × 106S m-1and 2.7 V respectively. A Ni-S/Ni current collector can provide excellent cycling stability with no electrochemical corrosion in the AIBs. The AIBs fabricated using a Ni-S/Ni current collector exhibits a specific capacity of 65 mAh/g at 1 A g-1, high coulombic efficiency of 99% and cyclability of at least 2000 cycles. Moreover, the total cost of the Ni-S/Ni current collector can be limited to less than 3.3 USD/m2. The comprehensive performances of these AIBs are better than most reported results so far, which indicates that this method can advance the commercialization of AIBs.