Biomimetic protein structural transitions regulate activation and inhibition of the broad-spectrum bactericidal activity of cationic nanoparticles.

The development of cationic polymers as alternative materials to antibiotics necessitates addressing the challenge of balancing their antimicrobial activity and toxicity. Here we propose a precise switching strategy inspired by biomimetic voltage-gated ion channels, enabling controlled activation and inhibition of cationic antimicrobial functions through protein conformational transitions in diverse physiological environments. Following thermodynamic studies on the specific recognition between mannose end groups on polycations and concanavalin A (ConA), we synthesized a type of ConA-polycation nanoparticle. The nanoparticle was inhibited under neutral conditions, with cationic moieties shielded by ConA's ß-sheet. This shielding suppresses their antimicrobial activity, thereby ensuring satisfactory biocompatibility. In mildly acidic environments, however, the transition of a portion of ConA to an α-helix conformation exposed cations at the particle periphery, activating antibacterial functionality. Compared to inhibited nanoparticles, those in the activated state exhibited a 32-256 times reduction in the minimum bactericidal concentration against bacteria and fungi (2-16 µg/mL). In a murine acute pulmonary infection model, intravenous administration of inhibited nanoparticles effectively reduced bacterial counts by 4-log within 12 h. The biomimetic design, regulating cationic antimicrobial functionality through the alteration in protein secondary structure, significantly retards bacterial resistance development, holding great promise for intelligent antimicrobial materials. STATEMENT OF SIGNIFICANCE: Cationic antimicrobial polymers exhibit advantages distinct from antibiotics due to their lower propensity for resistance development. However, the presence of cationic moieties also poses a threat to healthy cells and tissues, significantly constraining their potential for clinical applications. To address this challenge, we propose a biomimetic strategy that mimics voltage-gated ion channels to activate the antimicrobial functionality of cations selectively in bacterial environments through the conformational transitions of proteins between ß-sheets and α-helices. In healthy tissues, the antimicrobial functionality is inhibited, ensuring satisfactory biocompatibility. Antimicrobial cationic materials capable of intelligent switching between an activated state and an inhibited state in response to environmental changes offer an effective strategy to prevent the development of resistance and mitigate potential side effects.

Remove elemental mercury from simulated flue gas by CeO2-modified MnOx/HZSM-5 adsorbent.

In this study, we synthesized a Ce-modified Mn/HZSM-5 adsorbent via the ultrasound-assisted impregnation for Hg0 capture. Given the addition of 15% CeO2, ~ 100% Hg0 efficiency was reached at 200 °C, suggesting its promotional effect on Hg0 removal. The doped Ce introduced additional chemisorbed oxygen species onto the adsorbent surfaces, which facilitated the oxidation of Hg0 to HgO. Even though adding CeO2 led to a weakened adsorbent acidity, yet it appeared that this negative affect could be completely overcome by the enhanced oxidative ability, which finally endowed Ce-modified Mn/HZSM-5 with a satisfactory Hg0 removal performance within the whole investigated temperature range. During the Hg0 capture process, chemisorption was predominant with Mn4+operating as the main active site for oxidizing Hg0 to Hg2+. Finally, the 15Ce-Mn/HZSM-5 adsorbent exhibited good recyclability and stability. However, its tolerance to H2O and SO2 appeared relatively weak, suggesting that some modification should be conducted to improve its practicality.

Precision Dosing of Antibiotics and Potentiators by Hypoxia-Responsive Nanoparticles for Overcoming Antibiotic Resistance in Gram-Negative Bacteria.

The stalling development of antibiotics, especially against intrinsically resistant Gram-negative pathogens associated with outer membranes, leads to an emerging antibiotic crisis across the globe. To breathe life into existing drugs, we herein report a hypoxia-responsive nanoparticle (NP) that encapsulates a hydrophobic antibiotic, rifampicin, and a cationic potentiator, polysulfonium. The simultaneous release of antibiotics and potentiators can be promoted and inhibited in response to the severity of bacterial-induced hypoxia, leading to antimicrobial dosing in a precision manner. Under the synergism of polysulfoniums with membrane-disruption capability, the NPs can intensively decrease the antibiotic dose by up to 66-95% in eliminating planktonic Gram-negative P. aeruginosa bacteria and achieve an 8-log reduction of bacteria in mature biofilms at rifampicin MIC. The NP formulation demonstrates that precision dosing of antibiotics and potentiators regulated by hypoxia provides a promising strategy to maximize efficacy and minimize toxicity in treating Gram-negative bacterial infection.

Microbial community succession and their relationship with the flavor formation during the natural fermentation of Mouding sufu.

Mouding sufu, a traditional fermented soybean product in China, has been recognized by the public in the southwestern regions of China. To reveal the microbial community succession and their relationship with the flavor formation during the natural fermentation of Mouding sufu, microbial community, non-volatile flavor compounds and volatile flavor compounds were analyzed by high-throughput sequencing, high-performance liquid chromatography, gas chromatography ion migration spectroscopy, respectively. The results showed that Lactobacillus and Klebsiella were the most abundant bacterial genus, whereas the main fungal genera were unclassified-f-Dipodascaeae and Issatchenkia. In addition, Glutamic acid, Aspartic acid, Alanine, Valine, Lysine, Histidine, lactic acid, succinic acid, and acetic acid were the main non-volatile flavor substances. Furthermore, the taste activity values of glutamic acid, aspartic acid and lactic acid reached 132, 68.9, 18.18 at H60, respectively, meaning that umami and sour were the key taste compounds. Simultaneously, ethyl 3-methylbutanoate-M, ethyl propanoate, methyl 2-methylbutanoate, ethyl 2-methylbutanoate, ethyl 3-methylbutanoate-D, ethyl isobutyrate, linalool-M, linalool-D, cis-4-heptenal, 2-methylpropanal were the characteristic volatile flavor of Mouding sufu. Finally, correlation analysis showed that g__Erwinia and g__Acremonium correlated with most of the key aroma compounds. 20 bacteria and 21 fungi were identified as core functional microbe for Mouding sufu production.

Symmetry breaking and competition effect in phase transitions.

This study is started from a photon-magnon model with a competition effect of the level attraction and repulsion, its Hermiticity is mainly decided by a phase-dependent and asymmetric coupling factor, namelyφ = 0 for Hermitian andϕ=πfor non-Hermitian. Then an extensional study predicts the quantum critical behaviors using an Hermitian and even no-Hermitian photon-spins model with an additional second-order drive. The numerical results firstly indicate that this coupling phaseφcan function the protective effect on quantum phase transitions (QPTs), and the new tricritical points can not only be modulated by this nonlinear drive, but also be influenced by the dissipation and the collective decoherence. Secondly, this competition effect can also induce a reversal of the value of order parameters between the positive and negative. This study can also bring more important results of QPTs toward the issue of symmetry breaking and non-Hermiticity.

Screening and identification of biogenic amine oxidase producing strains in Sanchuan Ham and their effect on biogenic amine accumulation.

Sanchuan ham is a kind of popular fermented meat product in China. To understand the role of microorganisms in reducing the accumulation of Biogenic amine (BA) during ham fermentation. Biogenic amine oxidase-producing strains were screened and identified using color development method on double-layered plate, oxidase test, high-performance liquid chromatography (HPLC), physiological, biochemical methods, and 16 S rDNA. And then a model for simulated fermentation of Sanchuan ham was developed using the strains as single or mixed starter cultures. The results showed that two biogenic amine oxidase-producing strains were identified as Enterococcus faecium and Enterococcus faecalis from Sanchuan ham by compared to the NCBI database. And the mixed starter cultures showed a more remarkable effect on the decreased production of BA compared to single starter cultures, especially cadaverine and tyramine. The cadaverine was decreased from 92.74 ± 2.44 mg/Kg to 53.95 ± 2.69 mg/Kg and tyramine was decreased from 94.23 ± 3.42 mg/kg to 57.24 ± 3.51 mg/kg in mixed starter cultures than the control group. These results indicate exist biogenic amine oxidase-producing strains could decrease the accumulation of BA in Sanchuan ham. This study reveals important findings for improving the safety and health of Sanchuan ham and other fermented meat products. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05419-y.

Mechanism of biogenic amine synthesis of Enterococcus faecium isolated from Sanchun ham.

Sanchuan ham, produced in Yunnan, China, is food with ethnic characteristics favored by consumers. However, it can contain biogenic amines such as tyramine that are harmful to health, and the synthesis mechanism of biogenic amines in Sanchuan ham is not clear. This study focuses on the regulation of biogenic amine synthesis by quorum sensing. We used high-performance liquid chromatography to detect the content of biogenic amine in different kinds of ham and found that the content of biogenic amine in Sanchuan ham was higher than that in others. Tyramine-producing strain isolated from Sanchuan ham was identified as Enterococcus faecium. By monitoring the growth and tyramine synthesis of Enterococcus faecium under cultured conditions, the results found that high temperature and low salt increased tyramine production by E. faecium. After seven exogenous amino acids were applied to E. faecium, only tyrosine could promote the production of tyramine in E. faecium, and tyramine could not be synthesized in E. faecium until a certain amount was reached, indicating the presence of microbial quorum sensing signal molecules in the synthesis of tyramine in E. faecium. Untargeted metabolomics analysis of the differential metabolites produced by E. faecium showed that the contents of some peptides, especially alanyl-leucine, were significantly increased. Further experiments with synthetic alanyl-leucine illustrated that alanyl-leucine activated the expression of tyrosine decarboxylase (tyrDC), thereby regulating the synthesis of tyramine by E. faecium. Alanyl-leucine acted as quorum sensing signal molecules for biogenic amine synthesis by E. faecium, which provided a theoretical basis for reducing biogenic amine accumulation in ham. It is beneficial to control the content of biogenic amines in ham in the future.

Kondo effect and RKKY interaction assisted by magnetic anisotropy in a frustrated magnetic molecular device at zero and finite temperature.

Molecular magnetic compounds, which combine the advantages of nanoscale behaviors with the properties of bulk magnetic materials, are particularly attractive in the fields of high-density information storage and quantum computing. Before molecular electronic devices can be fabricated, a crucial task is the measurement and understanding of the transport behaviors. Herein, we consider a magnetic molecular trimer sandwiched between two metal electrodes, and, with the aid of the sophisticated full density matrix numerical renormalization group (FDM-NRG) technique, we study the effect of magnetic anisotropy on the charge transport properties, illustrated by the local density of states (LDOS, which is proportional to the differential conductance), the Kondo effect, and the temperature and inter-monomer hopping robustness. Three kinds of energy peaks are clarified in the LDOS: the Coulomb, the Kondo and the Ruderman-Kittel-Kasuya-Yosida (RKKY) peaks. The local magnetic moment and entropy go through four different regimes as the temperature decreases. The Kondo temperature TK could be described by a generalized Haldane's formula, revealing in detail the process where the local moment is partially screened by the itinerant electrons. A relationship between the width of the Kondo resonant peak WK and TK is built, ensuring the extraction of TK from WK in an efficient way. As the inter-monomer hopping integral varies, the ground state of the trimer changes from a spin quadruplet to a magnetically frustrated phase, then to an orbital spin singlet through two first order quantum phase transitions. In the first two phases, the Kondo peak in the transmission coefficient reaches its unitary limit, while in the orbital spin singlet, it is totally suppressed. We demonstrate that magnetic anisotropy may also induce the Kondo effect, even without Coulomb repulsion, hence it is replaceable in the many-body behaviours at low temperature.

Broad-Spectrum Bactericidal Activity and Remarkable Selectivity of Main-Chain Sulfonium-Containing Polymers with Alternating Sequences.

Incorporation of cationic groups into polymers represents one of the most widely used strategies to prepare antibacterial materials. Sulfonium, as a typical cationic moiety, displays potent antibacterial efficacy in the form of small molecules, however, has long underperformed in polymeric systems. Herein, we developed a series of alternating polysulfoniums, where the hydrophobicity of each alternating unit can be accurately tuned by altering the monomer precursors. Excellent antibacterial activity against a broad spectrum of clinically relevant bacteria, including Methicillin-resistant Staphylococcus aureus, can be obtained in the optimal compositions with minimum bactericidal concentrations in the range of 1.25-10 µg/mL, as well as negligible hemolytic effect at polymer concentrations even up to 10000 µg/mL. Bacteria do not readily develop resistance to polysulfoniums due to the antibacterial action is possibly the membrane disrupting mechanism. This work demonstrates sulfonium-based polymers with well-defined sequences can function as a promising candidate to combat drug-resistant bacterial infection.

A double responsive smart upconversion fluorescence sensing material for glycoprotein.

A novel strategy was developed to prepare double responsive smart upconversion fluorescence material for highly specific enrichment and sensing of glycoprotein. The novel double responsive smart sensing material was synthesized by choosing Horse radish peroxidase (HRP) as modal protein, the grapheme oxide (GO) as support material, upconversion nanoparticles (UCNPs) as fluorescence signal reporter, N-isopropyl acrylamide (NIPAAM) and 4-vinylphenylboronic acid (VPBA) as functional monomers. The structure and component of smart sensing material was investigated by transmission electron microscopy (TEM), Scanning electron microscopy (SEM), X-ray photoelectron spectroscopic (XPS) and Fourier transform infrared (FTIR), respectively. These results illustrated the smart sensing material was prepared successfully. The recognition characterizations of smart sensing material were evaluated, and results showed that the fluorescence intensity of smart sensing material was reduced gradually, as the concentration of protein increased, and the smart sensing material showed selective recognition for HRP among other proteins. Furthermore, the recognition ability of the smart sensing material for glycoprotein was regulated by controlling the pH value and temperature. Therefore, this strategy opens up new way to construct smart material for detection of glycoprotein.

Antimicrobial effect of Magnolia officinalis extract against Staphylococcus aureus.

BACKGROUND: The antimicrobial effect of Magnolia officinalis extract (MOE) against Staphylococcus aureus was investigated in a minced mutton system and the mechanisms of its antimicrobial activity were studied by light microscopy, transmission electron microscopy and scanning electron microscopy observations. RESULTS: MOE inoculation effectively inhibited the growth of S. aureus in minced mutton compared with that in control meat without MOE. The cell membrane of S. aureus treated with MOE showed structural disorganisation and cytoplasmic volume overflow. After 48 h of exposure to MOE, many S. aureus cells had completely collapsed. CONCLUSION: The antimicrobial mechanisms of MOE resulted mainly in cell membrane and wall damage, causing increased permeability of cell membranes or lysis of cell walls and loss of cellular constituents, impairment of structural components and changes in bacterial cell morphology.

Characterization of fermented black soybean natto inoculated with Bacillus natto during fermentation.

BACKGROUND: To make nutrients more accessible and further increase biological activity, cooked black soybeans were inoculated with Bacillus natto and fermented at 37 degrees C for 48 h. The changes in physiochemical properties of fermented black soybean natto were investigated. RESULTS: The inoculation procedure significantly increased moisture, viscosity, color, polyphenol compounds and anthocyanin, and significantly decreased hardness after 48 h fermentation. Fibrinolytic and caseinolytic protease, beta-glucosidase activities, TCA-soluble nitrogen, and ammonia nitrogen contents in the inoculated samples significantly increased as fermentation time increased. Genistin and daidzin concentrations gradually decreased with increased fermentation time. However, genistein and daidzein increased with fermentation time, which reached 316.8 and 305.2 microg g(-1) during 48 h fermentation, respectively. DPPH radical scavenging activities of the fermented black soybeans increased linearly with fermentation time and concentration. Compared with the soaked black soybeans and cooked black soybeans, the fermented black soybeans with B. natto resulted in higher scavenging activity towards DPPH radicals, which correlated well with the content of total phenols (r = 0.9254, P < 0.05) and aglycone isoflavone (r = 0.9861, P < 0.05). CONCLUSION: Black soybean natto fermented by B. natto has the potential to become a functional food because of its high antioxidant activity.