Dual-enzyme cascade colorimetric biosensor for safe, rapid on-site detection and detoxification of ochratoxins.

Ochratoxins, toxic mycotoxins present in food and feed, pose a threat to human health due to their various toxic effects. Developing a safe, convenient, and rapid on-site detection tool for monitoring ochratoxins is essential for food and environmental safety, especially in developing countries. Although numerous effective ochratoxin sensing and detection systems are available, most do not combine detoxification with detection capabilities.

Reshaping the Substrate-Binding Pocket of Leucine Dehydrogenase for Efficient Synthesis of l-Phenylglycine and Its Substituted Derivatives.

l-Leucine dehydrogenase (LeuDH)-mediated direct asymmetric reduction amination of prochiral α-keto acids represents an ideal approach for the synthesis of l-phenylglycine and its derivatives. However, limited substrate acceptance hinders their applications. Herein, we systematically investigated the substrate acceptance of LeuDHs for benzoylformic acid and its monosubstituted derivatives, revealing the correlation between substrate structure and enzyme activity.

Construction and Expression of Fc-FGF21 by Different Expression Systems and Comparison of Their Similarity and Difference with Efruxifermin by In Vitro and In Vivo Studies.

Non-alcoholic steatohepatitis (NASH) is a potential serious disease, which almost has no available medicine for effective treatment today. Efruxifermin is a bivalent Fc-FGF21 candidate drug developed by Akero Therapeutics that has shown promising results in preclinical and clinical trials for NASH and may be approved in future. However, it is produced by Escherichia coli (E.

Structure-guided engineering an (R)-transaminase from Mycobacterium neoaurum for efficient synthesis of chiral N-heterocyclic amines.

(R)-selective amine transaminases (R-ATAs) show considerable potential for the asymmetric synthesis of chiral drug intermediates. However, the low catalytic efficiency of natural R-ATAs toward bulky ketone substrates, such as N-heterocyclic compounds, severely limits its industrial application. In this study, five putative (R)-ATAs were mined from NCBI database, among which MnTA showed the highest activity for N-Boc-3-pyrrolidinone (1a) and N-Boc-3-piperidone (2a), and its crystal structure was performed.

Rational design of a 'two-in-one' immunogen DAM drives potent immune response against mpox virus.

The global outbreak of the mpox virus (MPXV) in 2022 highlights the urgent need for safer and more accessible new-generation vaccines. Here, we used a structure-guided multi-antigen fusion strategy to design a 'two-in-one' immunogen based on the single-chain dimeric MPXV extracellular enveloped virus antigen A35 bivalently fused with the intracellular mature virus antigen M1, called DAM. DAM preserved the natural epitope configuration of both components and showed stronger A35-specific and M1-specific antibody responses and in vivo protective efficacy against vaccinia virus (VACV) compared to co-immunization strategies.

Safety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects.

VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects, as well as the effect of food on the pharmacokinetics and safety of VV116. Three studies were launched sequentially: Study 1 (single ascending-dose study, SAD), Study 2 (multiple ascending-dose study, MAD), and Study 3 (food-effect study, FE).