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The continuous emergence of highly immune-evasive SARS-CoV-2 variants has challenged vaccine efficacy. A vaccine that can provide broad protection is desirable. We evaluated the immunogenicity of a series of monovalent and bivalent adenovirus-vectored vaccines containing the spikes of Wildtype (WT), Beta, Delta, Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.2.13, BA.3, BA.5, BQ.1.1, and XBB. Vaccination in mice using monovalent vaccines elicited the highest neutralizing titers against each self-matched strain, but against other variants were reduced 2− to 73-fold. A bivalent vaccine consisting of WT and BA.5 broadened the neutralizing breadth against pre-Omicron and Omicron subvariants except XBB. Among bivalent vaccines based on the strains before the emergence of XBB, a bivalent vaccine consisting of BA.2 and BA.5 elicited the most potent neutralizing antibodies against Omicron subvariants, including XBB. In mice primed with injected WT vaccine, intranasal booster with a bivalent vaccine containing XBB and BA.5 could elicit broad serum and respiratory mucosal neutralizing antibodies against all late Omicron subvariants, including XBB. In mice that had been sequentially vaccinated with WT and BA.5, intranasal booster with a monovalent XBB vaccine elicited greater serum and mucosal XBB neutralizing antibodies than bivalent vaccines containing XBB. Both monovalent and bivalent XBB vaccines induced neutralizing antibodies against EG.5. Unlike the antibody response, which is highly variant-specific, mice receiving either monovalent or bivalent vaccines elicited comparable T-cell responses against all variants. Furthermore, intranasal but not intramuscular booster induced antigen-specific lung resident T cells. This study provides insights into the design of the COVID-19 vaccine and vaccination strategies.

AbstractThe rising number of individuals diagnosed with type 2 diabetes is a global health concern. This chronic disease can lead to a diverse range of complications. In this study, we assessed the extracorporeal hypoglycemic mechanism as determined by the inhibitory activity of TGE (Fagopyrum tataricum grain crude extract) and TBE (Fagopyrum tataricum bran crude extract) on elevated blood glucose, oxidative stress and inflammatory response. In addition, to characterize hypoglycemic activity in vivo, we investigated the anti-diabetic effects of water—ethanol extracts of Fagopyrum tataricum grain and bran with flavonoid-rich and D-CI fractions in type 2 diabetic mice induced by streptozotocin and a high-fat/high-sugar diet. Moreover, compared with the TBE group through kit detection and in vitro test analysis, treatment of mice with TGE has a better ability of antioxidant activity, Reduce inflammatory overreaction, hypoglycemia, improving symptoms of type 2 diabetic mice and reducing organ damage. In conclusion, these findings yet indicate that TGE could be used to manage the disease, for the improvement of blood glucose level and exhibits antioxidant properties for type 2 diabetes. By providing a comprehensive review of the molecular mechanisms underlying glucose metabolism, oxidative stress, inflammation, organ structural damage, and insulin resistance in individuals with type 2 diabetes mellitus. Our findings not only offer a deeper understanding of these processes but also provide novel insights and theoretical guidance for the treatment of diabetes mellitus.

ABSTRACTDisruption of the cell cycle is a common strategy shared by many viruses to create a conducible cellular microenvironment for their efficient replication. We have previously shown that infection of cells with gammacoronavirus infectious bronchitis virus (IBV) activated the theataxia-telangiectasia mutated (ATM) Rad3-related (ATR)/checkpoint kinase 1 (Chk1) pathway and induced cell cycle arrest in S and G2/M phases, partially through the interaction of nonstructural protein 13 (nsp13) with the p125 catalytic subunit of DNA polymerase delta (pol δ). In this study, we show, by GST pulldown, co-immunoprecipitation and immunofluorescent staining, that IBV nsp12 directly interacts with the p50 regulatory subunit of pol δ in vitro and in cells overexpressing the two proteins as well as in cells infected with a recombinant IBV harbouring an HA-tagged nsp12. Furthermore, nsp12 from severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 was also able to interact with p50. These interactions play a synergistic role with nsp13 in the induction of S phase arrest. The fact that subunits of an essential cellular DNA replication machinery physically associate with two core replication enzymes from three different coronaviruses highlights the importance of these associations in coronavirus replication and virus-host interaction, and reveals the potential of targeting these subunits for antiviral intervention.

The covalent KRAS-G12C inhibitors (G12Ci) are rapidly changing the treatment landscape for advanced non-small cell lung cancer, but drug resistance remains a clinical challenge. Two recent studies have developed bispecific T cell engagers that form a link between T cells and tumor cells to selectively eliminate G12Ci-resistant cells.

Context: The dried fruits of Arctium lappa L. have been used in two forms in traditional Chinese medicine; crude and stir-heating Fructus Arctii. However, its processed product possesses better activity. Objective: In this study, the chemical constituents of both crude and processed Fructus Arctii and their antiproliferative activities were evaluated. Materials and methods: The seven main active components in crude and various processed Fructus Arctii were quantitatively determined using high-performance liquid chromatography (HPLC). According to the actual amount in crude and five processed samples, seven single components were combined as multi-component combinations with six different proportions. The antiproliferative activities of these compatibility component groups were examined using the CCK-8 assay. Results: During the heating process, the proportion of the seven main components changed dynamically. The contents of 3-caffeoylquinic acid (3-CQA), 3,5-dicaffeoylquinic acid (3,5-diCQA), and arctiin (ARC) declined, while the contents of 4-caffeoylquinic acid (4-CQA), 3,4-dicaffeoylquinic acid (3,4-diCQA), 4,5-dicaffeoylquinic acid (4,5-diCQA), and arctigenin (ARG) increased very significantly. Discussion and conclusions: The results also indicated that seven components in the processed samples had higher cytotoxic profiles against HL-60 cells than those in the crude sample. Therefore, the heating process may enhance the antitumor activity of Fructus Arctii by changing the proportion of active components.