We investigate the fragmentation chemistry of cationized carbohydrates using a combination of tandem mass spectrometry, regioselective labeling, and computational methods. Our model system is D-lactose. Barriers to the fundamental glyosidic bond cleavage reactions, neutral loss pathways, and structurally informative cross-ring cleavages are investigated. The most energetically favorable conformations of cationized D-lactose were found to be similar. In agreement with the literature, larger group I cations result in structures with increased cation coordination number which require greater collision energy to dissociate. In contrast with earlier proposals, the B -Y fragmentation pathways of both protonated and sodium-cationized analytes proceed via protonation of the glycosidic oxygen with concerted glycosidic bond cleavage. Additionally, for the sodiated congeners our calculations support sodiated 1,6-anhydrogalactose B ion structures, unlike the preceding literature. This affects the subsequent propensity of formation and prediction of B /Y branching ratio. The nature of the anomeric center (α/β) affects the relative energies of these processes, but not the overall ranking. Low-energy cross-ring cleavages are observed for the metal-cationized analytes with a retro-aldol mechanism producing the A ion from the sodiated forms. Theory and experiment support the importance of consecutive fragmentation processes, particularly for the protonated congeners at higher collision energies. Graphical Abstract ᅟ.

Fusarium graminearum is the main causal pathogen affecting small-grain cereals, and it produces deoxynivalenol, a kind of mycotoxin, which displays a wide range of toxic effects in human and animals. Bacterial strains isolated from peanut shells were investigated for their activities against F. graminearum by dual-culture plate and tip-culture assays. Among them, twenty strains exhibited potent inhibition to the growth of F. graminearum, and the inhibition rates ranged from 41.41% to 54.55% in dual-culture plate assay and 92.70% to 100% in tip-culture assay. Furthermore, eighteen strains reduced the production of deoxynivalenol by 16.69% to 90.30% in the wheat kernels assay. Finally, the strains with the strongest inhibitory activity were identified by morphological, physiological, biochemical methods and also 16S rDNA and gyrA gene analysis as Bacillus amyloliquefaciens. The current study highlights the potential application of antagonistic microorganisms and their metabolites in the prevention of fungal growth and mycotoxin production in wheat kernels. As a biological strategy, it might avoid safety problems and nutrition loss which always caused by physical and chemical strategies.

Acylpeptide hydrolases (APHs) catalyze the removal of N-acylated amino acids from blocked peptides. Like other prolyloligopeptidase (POP) family members, APHs are believed to be important targets for drug design. To date, the binding pose of organophosphorus (OP) compounds of APH, as well as the different OP compounds binding and inducing conformational changes in two domains, namely, α/β hydrolase and β-propeller, remain poorly understood. We report a computational study of APH bound to chlorpyrifosmethyl oxon and dichlorvos. In our docking study, Val471 and Gly368 are important residues for chlorpyrifosmethyl oxon and dichlorvos binding. Molecular dynamics simulations were also performed to explore the conformational changes between the chlorpyrifosmethyl oxon and dichlorvos bound to APH, which indicated that the structural feature of chlorpyrifosmethyl oxon binding in APH permitted partial opening of the β-propeller fold and allowed the chlorpyrifosmethyl oxon to easily enter the catalytic site. These results may facilitate the design of APH-targeting drugs with improved efficacy.

Influenza viruses are a major public health threat worldwide. The influenza hemagglutinin (HA) plays an essential role in the virus life cycle. Due to the high conservation of the HA stem region, it has become an especially attractive target for inhibitors for therapeutics. In this study, molecular simulation was applied to study the mechanism of a small molecule inhibitor (MBX2329) of influenza HA. Behaviors of the small molecule under neutral and acidic conditions were investigated, and an interesting dynamic binding mechanism was found. The results suggested that the binding of the inhibitor with HA under neutral conditions facilitates only its intake, while it interacts with HA under acidic conditions using a different mechanism at a new binding site. After a series of experiments, we believe that binding of the inhibitor can prevent the release of HA1 from HA2, further maintaining the rigidity of the HA2 loop and stabilizing the distance between the long helix and short helices. The investigated residues in the new binding site show high conservation, implying that the new binding pocket has the potential to be an effective drug target. The results of this study will provide a theoretical basis for the mechanism of new influenza virus inhibitors.Influenza virus is the causative agent of influenza, an infectious disease which usually leads to symptoms such as high fever, cough, headache, muscle and joint pain, sore throat, nasal discharge, and even a fatal illness similar to pneumonia 1-4 . Influenza viruses are divided into three types, type A, type B and type C, with influenza A virus presenting serious threats to public health worldwide due to its high mutation rate [5][6][7] . At present, two classes of drugs are approved by the Food and Drug Administration for treatment or chemoprophylaxis of influenza: matrix protein 2 (M2) inhibitors amantadine and rimantadine and the neuraminidase (NA) inhibitors (NAIs) oseltamivir and zanamivir 8,9 . However, with the wide use of these drugs, drug-resistant strains have appeared in succession 10 . Therefore, new antiviral targets with novel inhibition mechanism need to be developed.Hemagglutinin (HA), a viral receptor-binding and membrane-fusion glycoprotein involved in the invasion of influenza into host cells, plays an essential role in the life cycle of influenza A virus 3,11 . HA is a trimer of identical subunits, each of which consists of a variable membrane-distal receptor-binding globular domain (HA1) and a more conserved membrane-proximal helix-rich stem structure (HA2) 12 . Under acidic conditions, the residues on the outer surface of HA1 can be protonated easily, which leads to the large gathering of positive charges on the surface of HA 13,14 . With gradually increased charges, disaggregation of HA first occurs as the positive charges repel each other, followed by the entry of water into the interior of the protein causing further structural changes of HA2 13 . In the HA2 subunit, one short and one long α-helical segment are connected by a loop (helix-loo...