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The root of Panax notoginseng (Burk.) F.H. is one of the most famous natural medicines and functional foods for numerous diseases. The saponin constituents present in Panax notoginseng leaves (PNGL) demonstrate an elevated level of glycosylation in comparison to those in the roots, resulting in a significantly diminished bioavailability. In this study, we systematically screened nine recombinant thermostable glycosidases and identified a synergistic combination, namely Tpexy3 and Tpebgl3, to catalyze PNGL. At 70 °C, 2000 U of both glycosidases were added before and after 1 g of PNGL, yielding 650 mg of new fractions, of which ginsenosides Rg3, F2, CK, and PPD were identified as the major products. The enzymatic PNGL demonstrated a lipid droplet-lowering effect on the 3 T3-L1 lipid deposition model. Furthermore, the enzymatic PNGL exhibited significant inhibitory effects on weight gain, hyperlipidemia, hyperglycemia, and inflammation in high-fat diet (HFD) mice. Importantly, the enzymatic PNGL restored the HFD-induced increase in the Firmicutes/Bacteroidetes (F/B) ratio and promoted the growth of beneficial gut microbes with anti-inflammatory properties, improved lipid metabolism, and short-chain fatty acid production. These results strongly indicate that enzyme-catalyzed pretreatment of PNGL can effectively enhance its bioavailability and anti-obesity effects. Biological enzyme catalysis not only provides technical support for the development of specific functional products but also promotes the efficient and high-value utilization of natural product resources.

It is generally believed that there is a great relationship between hangover and the age of Baijiu. However, what factors make Baijiu (stored for a long time) feel better after drinking has not been well explained. In this study, ethanol metabolism, oxidation stress, inflammation and release of inhibitory neurotransmitter were selected as the indicator of hangover. The results showed that the longer the age of Baijiu, the higher the antioxidant and anti-inflammatory levels, the less damage to the liver of mice. In addition, we also found that the longer the age of Baijiu, the faster the ethanol metabolism rate, the smaller the impact on the brain. A correlation analysis on Baijiu ingredients and hangover related indicators was conducted. These results showed that ethyl acetate, n-butanol, n-hexanol, butyl acetate, ethyl octanoate, isovaleric acid, 2-hydroxypropionic acid had a great correlation with all hangover related indicators.

Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants have seriously attacked the antibody barrier established by natural infection and/or vaccination, especially the recently emerged BQ.1.1 and XBB.1. However, crucial mechanisms underlying the virus escape and the broad neutralization remain elusive. Here, we present a panoramic analysis of broadly neutralizing activity and binding epitopes of 75 monoclonal antibodies isolated from prototype inactivated vaccinees. Nearly all neutralizing antibodies (nAbs) partly or totally lose their neutralization against BQ.1.1 and XBB.1. We report a broad nAb, VacBB-551, that effectively neutralizes all tested subvariants including BA.2.75, BQ.1.1, and XBB.1. We determine the cryoelectron microscopy (cryo-EM) structure of VacBB-551 complexed with the BA.2 spike and perform detailed functional verification to reveal the molecular basis of N460K and F486V/S mutations mediating the partial escape of BA.2.75, BQ.1.1, and XBB.1 from the neutralization of VacBB-551. Overall, BQ.1.1 and XBB.1 raised the alarm over SARS-CoV-2 evolution with unprecedented antibody evasion from broad nAbs elicited by prototype vaccination.

Summary: SARS-CoV-2 Omicron BA.2.75 subvariant has evolved to a series of progeny variants carrying several additional mutations in the receptor-binding domain (RBD). Here, we investigated whether and how these single mutations based on BA.2.75 affect the neutralization of currently available anti-RBD monoclonal antibodies (mAbs) with well-defined structural information. Approximately 34% of mAbs maintained effective neutralizing activities against BA.2.75, consistent with those against BA.2, BA.4/5, and BA.2.12.1. Single additional R346T, K356T, L452R, or F486S mutations further facilitated BA.2.75-related progeny variants to escape from broadly neutralizing antibodies (bnAbs) at different degree. Only LY-CoV1404 (bebtelovimab) displayed a first-class neutralization potency and breadth against all tested Omicron subvariants. Overall, these data make a clear connection between virus escape and antibody recognizing antigenic epitopes, which facilitate to develop next-generation universal bnAbs against emerging SARS-CoV-2 variants.