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Compared with defect-free FeO x , the ultrafine FeO x in the FeO x (0.03)@HG-110 with abundant surface defects shows lower energy barrier and higher OER activity. [Display omitted] • The FeO x (0.03)@HG-110 exhibits an OER overpotential as low as 342 mV at 10 mA cm−2. • The average particle size of FeOx is ca. 1.6 nm. • FeO x (0.03)@HG-110 possesses a low E a of 35.9 kJ mol−1. • The rate-determining step is *O → *OOH with the energy barriers of 0.79 eV. Development of earth-abundant and robust oxygen evolution reaction (OER) catalysts is imperative for cost-effective hydrogen production via water electrolysis. Herein, we report ultrafine iron (oxy)hydroxide nanoparticles with average particle size of 2.6 nm and abundant surface defects homogeneously supported on oleum-treated graphite (FeO x (n)@HG-T), providing abundant active sites for the OER. The optimal FeO x (0.03)@HG-110 exhibits high electrocatalytic OER activity and excellent stability. Electrochemical testing results and theoretical calculations reveal that the outstanding OER activity of FeO x (0.03)@HG-110 is due to its stronger charge transfer ability and lower OER energy barrier than defect-free FeO x nanoparticles. This work demonstrates that the OER performance of oxyhydroxide-based electrocatalysts can be improved by surface defect engineering. [ABSTRACT FROM AUTHOR]

In this work, a new glucose oxidase-N-succinyl chitosan (GOD-NSCS) nanospheres was prepared through the immobilization of glucose oxidase (GOD) on N-succinyl chitosan (NSCS) nanospheres. Compared to the free GOD, GOD-NSCS nanospheres demonstrated the excellent anti- Colletotrichum gloeosporioides activity with the EC 50 values of 211.2 and 10.7 μg/mL against mycelial growth and spores germination. The computational biology analysis demonstrated that the substrate presented the similar binding free energy with GOD-NSCS nanospheres (−27.64 kcal/mol) compared with the free GOD (−24.04 kcal/mol), indicating that GOD-NSCS nanospheres had the same oxidation efficiency and produced more H 2 O 2. Moreover, the enzyme activity stability of GOD-NSCS nanospheres could be prolonged to 10 d. The cell membrane was destructed by the treatment of H 2 O 2 produced by GOD, leading to the cell death. In vivo test, GOD-NSCS nanospheres treatment significantly prolonged the preservation period of mangoes 2-fold. Collectively, these results suggested that GOD-NSCS nanospheres suppresses anthracnose in postharvest mangoes by inhibiting the growth of C. gloeosporioides and might become a potential natural preservative for fruits and vegetables. • GOD-NSCS nanospheres was prepared. • The nanospheres had the better oxidation efficiency and produced more H 2 O 2. • GOD-NSCS nanospheres presented the excellent anti- C. gloeosporioides activity. • The shelf life of mangoes could be significantly prolonged by GOD-NSCS nanospheres. [ABSTRACT FROM AUTHOR]

This paper presented an effective method that utilized scrap rubber as the precursor to prepare porous activated carbons by the pyrolysis and KOH activation processes. Adjusting the activation temperature can tailor the textural characteristics of the resulting activated carbon, thus tuning the energy storage performance of the activated carbon, including methane storage behavior and electrochemical performance. The as-obtained carbon materials possessed hierarchical porous structure, and the methane adsorption data were analyzed by Langmuir, Langmuir-Freundlich and D-A models, respectively, among which the D-A model fitted the data best. The greatest storage capacity (110.39 mg/g, D-A model) was obtained for the sample AC-750 due to its highest SSA and abundant micropores. Furthermore, the hierarchical porous activated carbon electrode exhibited good rate performance (capacitance retention rate at above 86% as the charge/discharge current density increased by 40 times). [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusion and Implications At present, the inhibition of staphyloxanthin biosynthesis has emerged as a prominent strategy in combating methicillin‐resistant Staphylococcus aureus (MRSA) infection. Nonetheless, there remains a limited understanding regarding the bio‐structural characteristics of staphyloxanthin biosynthetic enzymes, as well as the molecular mechanisms underlying the interaction between inhibitors and proteins. Furthermore, the functional scope of these inhibitors is relatively narrow.In this study, we address these limitations by harnessing the power of deep learning techniques to construct the 3D structure of diapophytoene desaturase (CrtN). We perform efficient virtual screening and unveil alnustone as a potent inhibitor of CrtN. Further investigations employing molecular modelling, site‐directed mutagenesis and biolayer interferometry (BLI) confirmed that alnustone binds to the catalytic active site of CrtN. Transcriptomic analysis reveals that alnustone significantly down‐regulates genes associated with staphyloxanthin, histidine and peptidoglycan biosynthesis.Under the effects of alnustone, MRSA strains exhibit enhanced sensitivity to various antibiotics and the host immune system, accompanied by increased cell membrane permeability. In a mouse model of systemic MRSA infection, the combination of alnustone and antibiotics exhibited a significant therapeutic effect, leading to reduced bacterial colony counts and attenuated pathological damage.Alnustone, as a natural inhibitor targeting CrtN, exhibits outstanding antibacterial properties that are single‐targeted yet multifunctional. This finding provides a novel strategy and theoretical basis for the development of drugs targeting staphyloxanthin producing bacteria. [ABSTRACT FROM AUTHOR]

The generation of guaiacol by Alicyclobacillus acidoterrestris (A. acidoterrestris) in fruit juices negatively affects public health and causes severe environmental pollution. Therefore, the sensitive detection and efficient degradation of guaiacol in real samples are crucial. Here, we develop an electrochemical sensor utilizing a copper single-atom nanozyme (CuN 4 -G) to detect and degrade guaiacol at the picomolar level. Density functional theory (DFT) calculations verify that the bonding electron coupling effect in the CuN 4 -G facilitates rapid electron transfer, enhances electrical conductivity, and provides abundant active sites, thereby leading to exceptional catalytic performance. Moreover, CuN 4 -G demonstrates a K m value similar to that of natural laccase but a higher V max , highlighting its potential as a highly efficient biocatalyst. The CuN 4 -G-based electrochemical sensor achieves a detection from 5 to 50,000 pM for guaiacol, with a 1.2 pM (S/N = 3) detection limit. Additionally, CuN 4 -G-modified electrodes display high selectivity and excellent stability. CuN 4 -G nanozyme can keep its activity in conditions of pH (3–9), temperature (30–90 °C), ionic strength (0–400 mM), and organic solvent (0–50% (v/v)), overcoming the deficiencies of natural enzymes. Furthermore, our electrochemical sensor can not only accurately detect guaiacol, but also degrade it in actual fruit juice samples infected by A. acidoterrestris , demonstrating its potential applications in food and environmental monitoring. [ABSTRACT FROM AUTHOR]

In previous literature, it was found that the activity of New Delhi Metallo-β-lactamase-1 (NDM-1) was inhibited by 2,6-dipicolinic acid (DPA) derivatives. To identify the mechanism of interaction between the inhibitors and NDM-1, molecular dynamics simulations were performed for the complex systems. Via the molecular modelling, inhibitors were found to be able bind to the region of catalytic activity of NDM-1. However, the detailed binding sites of the inhibitors differed with their structures. It was determined that His189, Lys211, Met248, Ser249, His250, and Ser251 are key residues for the binding of inhibitor 36 with NDM-1, and Asp124 is the only critical residue in the NDM-1-DPA complex. Furthermore, because of the interaction of the benzene ring in inhibitor 36 with the side chain of Lys211, inhibitor 36 can form 4 strong hydrogen bonds with protein. For the NDM-1-DPA complex, owing to the absence of the aniline group, DPA can only form a weak interaction with the residues around the binding site of NDM-1, except for Asp124, leading to a weaker inhibitory activity. Therefore, we believe that the strong interaction of the inhibitor with Lys211 results in effective inhibition, and the aniline group is the element required for the inhibitory activity. [ABSTRACT FROM AUTHOR]

Botrytis cinerea (B. cinerea) may cause severe decay in fruits and vegetables. In this paper, we found a food-borne compound ginsenoside CK (GCK) (from Ginseng) demonstrating excellent anti- B. cinerea activity and investigated its underlying inhibitory mechanism. The computational biology methods and bioactivity assays revealed that GCK markedly inhibited the bioactivity of sterol 14α-demethylase cytochrome P450 (CYP51) in B. cinerea with a competitive inhibitory mechanism (IC 50 = 14.45 μM). In vitro tests showed that GCK (64 × 10−3 g L−1) limited the mycelial growth of B. cinerea through inhibiting CYP51 activity by 85.92%. Notably, GCK treatment decreased the bioactivity of CYP51, thereby increasing cell membrane permeability that led to the death of B. cinerea. Moreover, GCK (64 × 10−3 g L−1) treatment reduced the decay of cherry tomatoes by 89.24% compared with those of blank control group. Our research revealed that the food-borne substance GCK could inhibit B. cinerea , prolonging the shelf life of cherry tomatoes. Thus, GCK has the potential to be applied in the preservation of fruits as an antifungal agent. [Display omitted] • GCK exhibited the excellent anti-CYP51 activity of Botrytis cinerea. • GCK influenced the catalytic activity of CYP51 as the competition inhibitory. • GCK hindered the growth of Botrytis cinerea by inhibiting CYP51. • The shelf life of tomato infection model could be prolonged by GCK. [ABSTRACT FROM AUTHOR]

In this study, the mechanism of apigenin inhibition was explored using molecular modelling, binding energy calculation, and mutagenesis assays. Energy decomposition analysis indicated that apigenin binds in the gap between domains 3 and 4 of PLY. Using principal component analysis, we found that binding of apigenin to PLY weakens the motion of domains 3 and 4. Consequently, these domains cannot complete the transition from monomer to oligomer, thereby blocking oligomerisation of PLY and counteracting its haemolytic activity. This inhibitory mechanism was confirmed by haemolysis assays, and these findings will promote the future development of an antimicrobial agent. [ABSTRACT FROM AUTHOR]

In this work, by using high throughput virtual screening and bioactivity assays, this work revealed that three natural compounds, mulberrin (Mul) exhibiting the highest anti-CYP51 activity, isoxanthohumol and (s)-isopsoralen markedly inhibited 14α-demethylase (a pivotal biosynthetic enzyme involved in the biosynthesis of ergosterol) in Colletotrichum gloeosporioides. Results of computational biology analysis demonstrated that, among the three inhibitors bound to the catalytic pocket of CYP51, Mul showed a closer distance with heme in CYP51 and a stronger binding free energy with CYP51. In vitro tests, Mul demonstrated excellent anti- Colletotrichum gloeosporioides activity by inhibiting CYP51 activity. Notably, Mul treatment decreased the bioactivity of CYP51, thereby increasing cell membrane permeability and cell death. Moreover, Mul treatment significantly prolonged the preservation period of fruits. These results suggest that Mul suppresses anthracnose in postharvest mango by inhibiting the growth of Colletotrichum gloeosporioides and can be used as a potential natural preserving agent. • Mul exhibited the excellent anti-CYP51 of C. gloeosporioides activity. • Mul binds to the catalytic active pocket of CYP51 as the competition inhibitory. • Mul apparently inhibit the growth of C. gloeosporioides by the binding with CYP51. • The shelf life of fruit infection model could be significantly prolonged by Mul. [ABSTRACT FROM AUTHOR]

ATP-binding cassette (ABC) transporters are integral membrane proteins that utilised energy from ATP hydrolysis to translocate substrates across the membrane. In addition to the common nucleotide-binding domains (NBDs) and transmembrane domains (TMDs), the methionine ABC transporter has C-terminal regulatory domains (C2 domains) that belong to ACT protein family. When the amount of methionine in the cell is high, the transport stops. This phenomenon is called trans-inhibition. To understand how a trans-inhibited protein returns to an uninhibited, resting state, we performed steered molecular dynamic simulations with and without the substrates. From the simulations, we observed some important conformational changes in the whole ABC transporter, including the constriction in the translocation pathway in the TMDs and approach of the NBDs. However, the C2 domains behaved differently in two types of the simulations. These findings might help to explain the relationship of the conformational changes of the C2 domains with the rearrangements of the NBDs or TMDs, and provide a way to understand the trans-inhibition from an opposite direction. [ABSTRACT FROM AUTHOR]

Abstract: The protein α-hemolysin (α-HL) is a self-assembling exotoxin that binds to the membrane of a susceptible host cell. In this paper, experimental studies show that cyrtominetin (CTM) can inhibit the hemolytic activity of α-HL. To understand how CTM can affect hemolytic activity, molecular dynamics simulations were carried out for α-HL–CTM complex and these results were compared with the crystal structure of monomeric α-HL. With this approach, the analysis revealed that the inhibition of CTM involves CTM directly binding to α-HL. Due to the binding of CTM, the conformation of the critical “Loop” region was restrained. This mechanism was confirmed by the experimental data. These findings indicate that CTM hinders the lysis activity of α-HL through a novel mechanism. [Copyright &y& Elsevier]

To achieve the structural basis to produce a more accurate model of the catalytic active site of Stx2, we carried out molecular docking and molecular dynamics simulations of adenosine–Stx2 complex, and used the molecular mechanics/Poisson–Boltzmann surface area method to determine the associated free energy profiles. The results reveal that the electrostatic interactions play an important role in the stabilisation of the binding site of Stx2–adenosine, and the key residues of Ser113, Arg119, Arg125 and Arg170 in Stx2–adenosine complex are identified based on the residue decomposition analysis. With this approach, we are able to demonstrate that the substrate adenosine is located in the cavity formed by A-subunit, which is similar to the available experimental binding pattern of Stx2–adenine except for adenine being more close to the residues of Arg170, Tyr77 and Val78. The conformational difference that lies in adenosine is stabilised by the residues around the binding site of adenosine–Stx2, which leads to that the adenine base and furan ring of adenosine are dragged by the residues in the opposite direction during the catalytic process. The above results indicate that the residues around the binding site of adenosine in Stx2 should be used as catalytic active site to depurinate a specific adenine base from 28S rRNA. [ABSTRACT FROM PUBLISHER]

In this study, the binding of Bovine serum albumin (BSA) with three flavonoids, kaempferol-3- O-a-L-rhamnopyranosyl-(1-3)-a-L-rhamnopyranosyl-(1-6)-b-D-galacto- pyranoside (drug 1),kaempfol-7- O-rhamnosyl-3- O-rutinoside (drug 2)andkaempferide-7-O-(4'- O-acetylrhamnosyl)-3- O-ruti- noside (drug 3) is investigated by molecular docking, molecular dynamics (MD) simulation, and binding free energy calculation. The free energies are consistent with available experimental results and suggest that the binding site of BSA-drug1 is more stable than those of BSA-drug2 and BSA-drug3. The energy decomposition analysis is performed and reveals that the electrostatic interactions play an important role in the stabilization of the binding site of BSA-drug1 while the van der Waals interactions contribute largely to stabilization of the binding site of BSA-drug2 and BSA-drug3. The key residues stabilizing the binding sites of BSA-drug1, BSA-drug2 and BSA-drug3 are identified based on the residue decomposition analysis. [ABSTRACT FROM AUTHOR]

α-Hemolysin (Hla) is a self-assembling, channel-forming toxin that is secreted by Staphylococcus aureus and is central to the pathogenesis of pulmonary, intraperitoneal, intramammary, and corneal infections in animal models. In this study, we report that baicalin (BAI), a natural compound that lacks anti–S. aureus activity, could inhibit the hemolytic activity of Hla. Using molecular dynamics simulations and mutagenesis assays, we further demonstrate that BAI binds to the binding sites of Y148, P151, and F153 in the Hla. This binding interaction inhibits heptamer formation. Furthermore, when added to S. aureus cultures, BAI prevents Hla-mediated human alveolar epithelial (A549) cell injury. In vivo studies further demonstrated that BAI protects mice from S. aureus pneumonia. These findings indicate that BAI hinders the cell lysis activity of Hla through a novel mechanism of interrupting the formation of heptamer, which may lead to the development of novel therapeutics that aim against S. aureus Hla. [ABSTRACT FROM AUTHOR]

Abstract: The fabrication of the green polymer light-emitting diodes based on emission from the phosphorescent molecule fac tris(2-phenylpyridine) iridium doped into a polymeric binary-host is reported. The main host used in the PLEDs was a non-conjugated polymer, poly(9-vinyl carbazole) (PVK). To realize the balanced transport of the holes and the electrons, a conjugated polymer, poly(9,9-dioctylfluorene) (PFO) was used as the assisting host. According to the experimental results, we found that the PLEDs can achieve the balance in charge transport and the recombination zone is still confined in the emissive layer by controlling the ratio of PVK to PFO. The luminous efficiency is enhanced by >40% while the external quantum efficiency can be increased by >38% in a polymeric binary-host system as compared to those of traditional device configuration, which is attributed to the balanced transport of the charged carrier. [Copyright &y& Elsevier]

Abstract: We present the results of a systematic study on how the solvent processing affects the EL properties of a single emissive layer white PLED based on a polyfluorene derivative polymer. The EL spectrum of the device using solvent processing, peaked at 436, 572nm, shows a pure white emission and the luminous efficiency is enhanced, which is attributed to the presence of the crystalline polyfluorene induced by solvent processing. The crystalline polyfluorene that acts as the self-dopant enhances the blue emission and increases the purity of the white light. Most importantly, the charge transport is balanced after solvent processing, which favors improving the luminous efficiency. A light-emitting efficiency of 12cd/A is achieved after solvent processing, about 50% increase compared to the as-spincoated device. [Copyright &y& Elsevier]

In this work, a novel antifungal Nanoparticles (NPs), Fe 3 O 4 @Ce6/C6@silane, based on photodynamic therapy (PDT) with excellent anti- Botrytis cinerea activity was reported. Due to the remarkable photosensitization properties of Fe 3 O 4 @Ce6/C6@silane, singlet oxygen (1O 2) was generated from the photosensitizer Ce6 under red light irradiation, leading to the inhibitory activity of Fe 3 O 4 @Ce6/C6@silane against Botrytis cinerea. The half-maximal inhibitory concentrations (IC 50) of Fe 3 O 4 @Ce6/C6@silane towards spore germination and hyphal growth in Botrytis cinerea were 0.022611 and 0.014213 g L−1, respectively. 1O 2 generated from Ce6 was confirmed to be the actual antifungal active ingredient, not the irradiation itself. Furthermore, via the infection model involving construction of strawberries infected with Botrytis cinerea , it was found that Botrytis cinerea grew normally in strawberries from the blank and negative control groups, whereas strawberries treated with NPs under red light irradiation did not exhibit Botrytis cinerea growth within 8d of preservation. These results showed that Fe 3 O 4 @Ce6/C6@silane has an excellent inhibitory effect on Botrytis cinerea based on the release of 1O 2 from Ce6 and could be used as a potential photosensitized preserving agent for fruit storage. • Fe 3 O 4 @Ce6/C6@silane apparently inhibit Botrytis cinerea. • 1O 2 was generated from Fe 3 O 4 @Ce6/C6@silane under red light irradiation. • 1O 2 led to the inhibitory activity of Fe 3 O 4 @Ce6/C6@silane. • The shelf life of strawberries could be doubled by Fe 3 O 4 @Ce6/C6@silane. [ABSTRACT FROM AUTHOR]

Efficient multilayer white polymer light-emitting diodes (WPLEDs) with aluminum cathodes are fabricated. The multilayer structure is composed of a water soluble hole-injection layer, a toluene-soluble emissive layer, and an alcohol-soluble emissive layer. The polarity difference of the solvents used for spin coating these polymers allows for realization of the multilayer polymer structure. The recombination zone confined at the interface of the two emissive polymers avoids exciton quenching by electrodes, and white emission is realized by harvesting photons emitted from the two emissive polymers. A maximum luminous efficiency of 16.9 cd/A and a power efficiency of 11.1 lm/W are achieved for this WPLED. [ABSTRACT FROM AUTHOR]

The purpose of this study is to obtain a washable, nontoxic and safe green antibacterial preservation material that can be used for food preservation. Therefore, a water-soluble N -succinyl chitosan (NSC) was prepared by reacting succinic anhydride with chitosan, and lysozyme- N -succinyl chitosan (LSZ-NSC) was prepared using NSC loaded lysozyme (LSZ). The effect of NSC on lysozyme activity and antibacterial activity was studied. Lysozyme activity in LSZ-NSCs increased by 256% compared with the activity of free lysozyme, and bacteriostatic activity also increased, and increased significantly at low concentrations. The structure and stability of NSC and LSC-NSC were analyzed. The active group introduced by NSC was located on the C2–NH 2 group of chitosan. During the process of lysozyme loading, the secondary structure of lysozyme changed markedly, which may be one of the reasons for the change in lysozyme activity. Based to the characteristics of NSC and LSZ-NSC, these compounds were used as bacteriostatic materials in strawberry preservation. Both NSC and NSC-LSZ prolonged the shelf life of strawberry, and NSC-LSZ effectively extended the shelf life of strawberry by 3 days. This research provides a safe and feasible green bacteriostatic preservative material for the fresh storage of food. • A method for preparing green washable lysozyme-N-succinate chitosan is provided. • N-succinyl chitosan immobilization improved the activity of lysozyme. • Lysozyme-N-succinyl chitosan prolong the freshness of Strawberry for 3 days. [ABSTRACT FROM AUTHOR]

The efficient white polymeric light-emitting diodes based on a white emissive polymer doped with a red phosphorescent dopant were fabricated by spin-coating method. The emission spectrum of the device is broadened to cover the full visible region by doping the red phosphorescent dye and thereby realizes white emission with high color-rendering index (CRI). By controlling the contents of the doped electron-transporting 2-(4-biphenylyl)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole and the red phosphorescent dopant, a luminous efficiency as high as 5.3 cd/A and a power efficiency of 3 lm/W were obtained with a CRI of 92. [ABSTRACT FROM AUTHOR]

The most prevalent complication arising from skin injuries is bacterial infection, where pathogenic bacteria proliferate significantly at the wound site, leading to subsequent complications like septic shock and sepsis. Although antibiotics presently effectively manage wound infections caused by common bacteria, the escalating prevalence of antibiotic-resistant strains necessitates urgent novel approaches for addressing such infections. Here, we present CS9P1-RA, a dual functional hydrogel dressing, based on polyvinyl alcohol (PVA) matrix crosslinked through hydrogen bonding. CS9P1-RA combines chitosan (CS), a food-derived antibacterial agent, with the natural compound rosmarinic acid (RA) to specifically target skin injuries caused by MRSA. Computational and molecular biology assays illustrate RA's ability to selectively inhibit the activity of Staphylococcus aureus (S. aureus) serine/threonine phosphatase (Stp1), reducing the S. aureus pathogenicity. CS9P1-RA showcases exceptional antibacterial efficacy (MIC = 1 mg/mL) and demonstrates potency in reducing virulence (IC 50 = 7.424 μM on Stp1). Notably, it effectively curbs bacterial growth and accelerates wound healing in the mice model, thereby fulfilling the practical requirements for clinical applications. Moreover, the mechanical properties of CS9P1-RA ensure user comfort during treatment. This work introduces a fresh design paradigm for dressing materials, offering a promising solution for treating skin injuries inflicted by antibiotic-resistant bacterial infections. • A hydrogel dressing CS9P1-RA with the dual efficacy is prepared. • The anti-virulence factor RA exhibits the inhibitory activity of Stp1. • CS9P1-RA achieves the purpose of antibacterial activity and wound healing. • CS9P1-RA boasts outstanding mechanical properties, ensuring user comfort. [ABSTRACT FROM AUTHOR]

The emergence and worldwide dissemination of mobile tigecycline resistance genes tet(X3)/tet(X4) posed an enormous threat to the public health. Urgently, feasible strategies must be implemented to restore the clinical efficacy of tetracyclines and prolong the lifespan of existing drugs to address the emerging global antimicrobial resistance threat. Herein, versatile structural scaffolds of quinones for antibiotic adjuvants discovery enlightened a promising and underappreciated reservoir to circumvent the antibiotic resistance. 2-methoxy-1,4-naphthoquinone (MNQ) exhibited the potent potentiation (4 to 32-fold) with tetracyclines, along with effective inhibition on biofilm formation. Mechanistic studies revealed that MNQ synergistically operates with tetracyclines by inhibiting the enzymatic activity of Tet(X3)/Tet(X4) proteins through interaction with their active residues. Furthermore, exposure to MNQ significantly dissipate the proton motive force, leading to a cascade of membrane structural damage and metabolic homeostasis imbalance. Encouragingly, the MNQ-tetracyclines combination showcased substantial therapeutic benefits in two in vivo infection models, as evidenced by the reduced bacterial burden and mitigated pathological injury. Our findings propose a potential therapeutic option and a novel tetracyclines' adjuvant against drug-resistant pathogens carrying Tet(X3)/Tet(X4). [ABSTRACT FROM AUTHOR]

Background and purpose: The production of metallo‐β‐lactamases is a major mechanisms adopted by bacterial pathogens to resist carbapenems. Repurposing approved drugs to restore the efficacy of carbapenems represents an efficient and cost‐effective approach to fight infections caused by carbapenem resistant pathogens. Experimental approach: The nitrocefin hydrolysis assay was employed to screen potential New Delhi metallo‐lactamase‐1 (NDM‐1) inhibitors from a commercially available U.S. Food and Drug Administration (FDA) approved drug library. The mechanism of inhibition was clarified by metal restoration, inductively coupled plasma mass spectrometry (ICP‐MS) and molecular dynamics simulation. The in vitro synergistic antibacterial effect of the identified inhibitors with meropenem was determined by the checkerboard minimum inhibitory concentration (MIC) assay, time‐dependent killing assay and combined disc test. Three mouse infection models were used to further evaluate the in vivo therapeutic efficacy of combined therapy. Key results: Twelve FDA‐approved compounds were initially screened to inhibit the ability of NDM‐1 to hydrolyse nitrocefin. Among these compounds, dexrazoxane, embelin, candesartan cilexetil and nordihydroguaiaretic acid were demonstrated to inhibit all tested metallo‐β‐lactamases and showed an in vitro synergistic bactericidal effect with meropenem against metallo‐β‐lactamases‐producing bacteria. Dexrazoxane, embelin and candesartan cilexetil are metal ion chelating agents, while the inhibition of NDM‐1 by nordihydroguaiaretic acid involves its direct binding to the active region of NDM‐1. Furthermore, these four drugs dramatically rescued the treatment efficacy of meropenem in three infection models. Conclusions and implications: Our observations indicated that dexrazoxane, embelin, candesartan cilexetil and nordihydroguaiaretic acid are promising carbapenem adjuvants against metallo‐β‐lactamases‐positive carbapenem resistant bacterial pathogens. [ABSTRACT FROM AUTHOR]

Summary: Safe and suitable food preservatives can ensure food safety and reduce resource wastage. This paper focuses on the modification of chitosan (CS) using 2,2,6,6‐tetramethylpiperidine‐1‐oxyl radical (TEMPO)/laccase oxidation system and chitosanase. The experimental results showed that the aldehyde group content of the modified CS was increased by 83.3% and the water solubility increased by 4.5 times. In addition, the covalent binding with lysozyme (LSZ) also improved the inhibition effect and the diameter of the inhibition circle was increased by 3 mm. Applying the LSZ‐modified CS to the preservation of strawberries and Tremella fuciformis (T. fuciformis), it was found that the preservation time of strawberries could be extended by 2 days at room temperature, and the microbial spoilage of T. fuciformis was also inhibited. This study provided a CS derivative that could be used as a carrier of natural antibacterial agents, which increased application scope of CS and provided a basis for antimicrobial preservation of food. [ABSTRACT FROM AUTHOR]

Clostridium perfringens (C. perfringens) is an important foodborne pathogen that can cause diseases such as gas gangrene and necrotizing enteritis in a variety of economic animals, seriously affecting public health and the economic benefits and healthy development of the livestock and poultry breeding industry. Perfringolysin O (PFO) is an important virulence factor of C. perfringens and plays critical roles in necrotic enteritis and gas gangrene, rendering it an ideal target for developing new drugs against infections caused by this pathogen. In this study, based on biological activity inhibition assays, oligomerization tests and computational biology assays, we found that the foodborne natural component piceatannol reduced pore-forming activity with an inhibitory ratio of 83.84% in the concentration of 16 µg/mL (IC50 = 7.83 µg/mL) by binding with PFO directly and changing some of its secondary structures, including 3-Helix, A-helix, bend, and in turn, ultimately affecting oligomer formation. Furthermore, we confirmed that piceatannol protected human intestinal epithelial cells from the damage induced by PFO with LDH release reduced by 38.44% at 16 µg/mL, based on a cytotoxicity test. By performing an animal experiment, we found the C. perfringens clones showed an approximate 10-fold reduction in infected mice. These results suggest that piceatannol may be a candidate for anti-C. perfringens drug development. [ABSTRACT FROM AUTHOR]

[Display omitted] • Spectral and thermodynamic were used to resolve the ability of HE to permeate to DPPC liposomes. • Spectral method was used to resolve the good binding ability of HE to BSA. • Molecular dynamics simulations showed that HE has a good binding posture with HSA. • Elucidated the role and mechanism of HE in in vivo transport modeling. • To provide a reference for further improving the pharmacological mechanism of HE. Hesperidin (HE), a significant flavonoid polyphenolic compound present in citrus plants, exhibits diverse pharmacological effects. Considering the crucial involvement of biological membranes and transporter proteins in the transportation and biological processes of HE, it becomes essential to comprehend the potential mechanisms through which HE interacts with membranes and transporter proteins. In order to simulate the process of active molecule transport, a cell membrane model consisting of 1,2-dipalmitoyl-n- glycero -3-phosphatidylcholine (DPPC) and a transporter protein model of bovine serum albumin (BSA) were employed for investigation. The present study aimed to investigate the mechanism of action of hesperidin (HE) in DPPC and BSA using fluorescence quenching, Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The localization and interaction of HE within liposomes were also elucidated. Furthermore, the binding of BSA and HE was analyzed through UV/Vis absorption spectroscopy, fluorescence spectroscopy, infrared spectroscopy, and computational biology techniques. Computational biology analysis revealed that the binding between HE and BSA primarily occurred via hydrogen bonding and hydrophobic interactions. This study aimed to investigate the role and mechanism of HE in the DPPC cell membrane model and the BSA transporter protein model, thereby offering novel insights into the action of HE in DPPC and BSA. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, the geometrical structures, electronic structures, absorption and emission spectra of three series of oligomers containing thiophenes, siloles as well as both thiophene and siloles alternately, respectively, are comparatively studied by ab initio, B3LYP and TDDFT methods with basis set 6-31G(d).The results show that the highest occupied orbitals (HOMOs), the lowest unoccupied orbitals (LUMOs) of these oligomers increase and decrease, respectively, as the molecular chain lengths increase. The HOMO–LUMO energy gaps and the lowest excitation energies of these oligomers are proportional to reciprocal of repeat units. Better descriptions of between the lowest excitation energies and molecular chains for studied oligomers are obtained by Kuhn equation. Their linear relationships are obtained, so the HOMO–LUMO energy gaps and the lowest excitation energies of corresponding polymers are obtained. The HOMO and LUMO energies, the vertical excited energies for the ground states and the first excited states of hybrid oligomers lie between thiophene and silole oligomers while oligomers contain the same number of units. [Copyright &y& Elsevier]

The purpose of this study is to develop a green and safe chitosan‐based preservative which can be applied in strawberry preservation. Chitosan (CS) was treated by 2,2,6,6‐tetramethylpiperidine oxygen radical/laccase oxidation system (TEMPO/laccase oxidation system), which was mainly used to prepare TEMPO/laccase chitosan (TLCS). Furthermore, on this basis, the structure and performance of TLCS were also studied. The results showed that compared with CS, the solubility of TLCS improved, and the kinetic viscosity reduced significantly. Next, a cinnamaldehyde‐TEMPO/laccase chitosan (CIN‐TLCS) antibacterial agent was prepared by covalently combining the aldehyde group in cinnamaldehyde (CIN) and the amino group in CS. It was found that CIN combined with TLCS through covalent bonds, which changed the structure and crystallinity of TLCS. In addition, the total antioxidant capacity of CIN‐TLCS also improved, which was necessary for the application of CIN‐TLCS in extending shelf life. Cytotoxicity experiments showed that CIN‐TLCS had no cytotoxicity. Furthermore, strawberries were used to explore the actual bacteriostatic and fresh‐keeping effects of CIN‐TLCS. The experiment found that CIN‐TLCS could maintain the freshness of strawberries at room temperature (23 ± 1°C) for 5 days and had positive effects on strawberry color, loss‐weight rate, hardness and pH. These results showed that CIN‐TLCS could be used as a potential preserving agent for fruit storage. Practical Application: To obtain a green, safe and effective food preservative, chitosan (CS) was modified by a 2,2,6,6‐tetramethylpiperidine oxygen radical/laccase oxidation system (TEMPO/laccase oxidation system) to get TEMPO/laccase chitosan (TLCS) and cinnamic aldehyde‐TEMPO/laccase chitosan (CIN‐TLCS). At the same time, the structure and antibacterial properties of TLCS and CIN‐TLCS were analyzed, and their possibility as a new green and safe strawberry preservative was studied. Compared with oxazolidine, imidazole and triazole commercial drugs, CIN‐TLCS has the advantages of low price, no pollution, no cytotoxicity and no drug resistance. [ABSTRACT FROM AUTHOR]

In this experiment, we designed an electrochemical sensor using penicillinase (Pen X)‐rhombus porous carbon (RPC) as the detection element and hematoxylin as the indicator to detect low concentrations of penicillin sodium (Pen G). A differential pulse voltammetry (DPV) method was used to detect Pen G in the concentration range of 10–8–10–5 mg·mL–1 under optimal experimental conditions. The results showed that the peak current value and the logarithm of Pen G concentration showed a good linear relationship (R2 = 0.9915), and the LOD was 2.68 × 10–7 mg·mL–1 (S/N = 3). The actual milk samples were detected by the addition method and compared with the high‐performance liquid phase method; no significant difference was found in the detection results. The working electrode prepared by cross‐linking method not only extends the service life of the sensor, but also improves the sensitivity and reproducibility of the sensor. It can also be used to detect the Pen G residue in the actual milk samples repeatedly. Practical Application: In this study, an electrochemical sensor for the rapid detection of penicillin sodium in milk was prepared, which has good sensitivity and fast detection speed. [ABSTRACT FROM AUTHOR]

[Display omitted] • Molecular dynamics simulations demonstrated a good binding pose of SA to HSA. • Elucidation of the good binding ability of SA to BSA using spectrum method. • Elucidation that BSA-SA has better inhibitory ability on α-amylase than SA. • Elucidation of the safe and non-toxic properties of SA and BSA-SA in cells. • A reference for further exploration of the stability of BSA-SA complex. As a major flavonoid polyphenolic compound in the stem of Hibiscus taiwanensis , syringaldehyde (SA) has numerous pharmacological effects. Nevertheless, owing to its less in-depth study, its application is limited. Within this work, the interactions between serum albumin and SA were elucidated by multispectral studies. The results of ultraviolet/visible absorption spectroscopy suggest that the conformation of serum albumin can be altered by binding with SA. Fluorescence spectroscopy indicates that SA forms complexes with serum albumin, quenching its fluorescence. This suggests that the fluorescent residues of serum albumin are situated at or near the binding site. Additionally, FT-IR results confirm that SA alters the secondary structure of BSA, specifically affecting the positions of both amide I and amide II bands. Via the computational biology analyses, it was confirmed that SA binds at the active site of serum albumin and nine residues form hydrophobic interactions. In addition, the cytotoxicity of SA to BRL-3A cells was also studied, and SA had almost no toxicity to the growth of BRL-3A cells. The complex has a higher α-amylase inhibition capacity than SA alone. To sum up, this work reveals that the interaction of SA with BSA induces a conformational alteration in BSA. It also proved that SA inhibits α-amylase more significantly and has great potential in hypoglycemia. [ABSTRACT FROM AUTHOR]

Single-atom manganese catalysts possess high stability in the oxygen reduction reaction (ORR) due to their lower Fenton reaction activity. Here, we employ N- and S-co-coordination strategy to modulate the microstructural Mn sites towards high-efficiency ORR. The fabricated Mn-N/S-C catalyst with isolated Mn-N 2 S 2 sites demonstrates a positive half-wave potential of 0.91 V for the ORR. The fabricated zinc–air battery with Mn-N/S-C as the cathode affords a maximal power density of 193 mW cm−2 and superior output stability. Moreover, the maximal power density is increased by 1.53 times compared with S-free Mn-N-C catalyst in anion exchange membrane fuel cells (AEMFCs). Both experimental characterizations and theoretical simulations unveil that the main active sites in the Mn-N/S-C should be Mn-N 2 S 2 moiety embedded into the graphene framework (Mn-N 2 S 2 G). Further computational results demonstrate that the S atom doping and asymmetry of structure lead to higher ORR activities of ortho-Mn-N 2 S 2 G than Mn-N 4 G, Mn-N 3 SG, para-Mn-N 2 S 2 G and Mn-NS 3 G. [Display omitted] • N- and S-co-coordination to isolated Mn sites improves the catalytic activity. • The Mn-N/S-C exhibits a positive half-wave potential of 0.91 V for the ORR. • The Mn-N/S-C-based zinc–air battery affords a peak power density of 193 mW cm−2. • The Mn-N/S-C-based AEMFC affords a peak power density of 247 mW cm−2. • Ortho-Mn-N 2 S 2 G shows higher activity than Mn-N 4 G, para-Mn-N 2 S 2 G and Mn-NS 3 G. [ABSTRACT FROM AUTHOR]

In recent years, to increase growth rate and prevent infectious diseases, an excessive use of antibiotics in livestock breeding processes has resulted in the presence of antibiotic residues in animal foods. In this experiment, a new kind of electrochemical sensor is prepared based on magnetic mesoporous hollow carbon microspheres (MHM) as a penicillinase (Pen X) adsorption carrier to rapidly detect penicillin sodium (Pen G), named Pen X/MHM/MGCE. The MHM‐adsorbed penicillinase can be separated from the solution by magnetic attraction and fixed on a magnetic glassy carbon electrode by physical adsorption, which is easy to operate and avoids the interference of a crosslinking agent at the active site of the enzyme. A differential pulse voltammetry (DPV) method is used to immerse the working electrode in test samples containing different concentrations of penicillin sodium solution with 0.5 mg/mL oxidized hematoxylin. According to the quantitative relationship between the current value and the concentration of penicillin sodium, the concentration of penicillin sodium in the tested samples can be determined. The detection range of the sensor is 10−8 to 10−2 mg/mL, the linear relationship is good (R2 = 0.9983), and the detection limit (LOD) is 2.655 × 10−7 mg/mL (S/N = 3). The detection of penicillin sodium in milk using a standard addition method shows good recovery. Furthermore, the proposed method has the advantages of a wide detection range, good enzyme immobilization capacity, good precision and stability, convenient cleaning, and recycling of solid materials. Thus, it can successfully achieve rapid detection in milk samples. Practical Application: The sensor provides a low detection limit and high recovery rate of electrode material; therefore, the sensor can realize the rapid and quantitative detection of penicillin sodium in milk. [ABSTRACT FROM AUTHOR]

Background and Purpose: Bacteria producing New Delhi metallo-β-lactamase-1 (NDM-1) are an increasing clinical threat. NDM-1 can inactivate almost all β-lactams and is not sensitive to any existing β-lactamase inhibitors. To identify effective inhibitors of the NDM-1 enzyme and clarify the mechanism of action, a "lead compound" for developing more potent NDM-1 inhibitors needs to be provided.Experimental Approach: Natural compounds were tested by enzyme inhibition screening to find potential inhibitors. MIC assays, growth curve assays, and time-kill assays were conducted to evaluate the in vitro antibacterial activity of pterostilbene and the combination of pterostilbene and meropenem. A murine thigh model and a mouse pneumonia model were used to evaluate the in vivo efficacy of combined therapy. Molecular modelling and a mutational analysis were used to clarify the mechanism of action.Key Results: Pterostilbene significantly inhibited NDM-1 hydrolysis activity in enzyme inhibition screening assays and effectively restored the effectiveness of meropenem in vitro with NDM-expressing isolates in antibacterial activity assays. In addition, the combined therapy effectively reduced the bacterial burden in a murine thigh model and protected mice from pneumonia caused by Klebsiella pneumoniae. By means of molecular dynamics simulation, we observed that pterostilbene localized to the catalytic pocket of NDM-1, hindering substrate binding to NDM-1 and reducing NDM-1 activity.Conclusions and Implications: These findings indicated that pterostilbene combined with meropenem may offer a new safe and potential "lead compound" for the further development of NDM-1 inhibitors. [ABSTRACT FROM AUTHOR]

Total antioxidant capacity (TAC) has become an important index to evaluate the food quality. Effective antioxidant detection has been the research hotspot of scientists. In this work, a novel three-channel colorimetric sensor array founded on Au 2 Pt bimetallic nanozymes for the discrimination of antioxidants in food was constructed. Benefiting from the unique bimetallic doping structure, Au 2 Pt nanospheres exhibited the excellent peroxidase-like activity with K m of 0.044 mM and V max of 19.37 × 10−8 M s−1 toward TMB. The density functional theory (DFT) calculation revealed that Pt atom in the doping system was active sites and there was no energy barrier in catalytic reaction which made Au 2 Pt nanospheres had excellent catalytic activity. Accordingly, a multifunctional colorimetric sensor array was constructed based on Au 2 Pt bimetallic nanozymes for rapid and sensitive detection of five antioxidants. Based on the different reduction ability of antioxidants, oxidized TMB could be reduced in different degrees. In the presence of H 2 O 2 , the colorimetric sensor array could generate differential colorimetric signals (fingerprints) by using TMB as the chromogenic substrate, which could be accurately discriminated through linear discriminant analysis (LDA) with a detection limit of <0.2 μM. The sensor array was able to the evaluate TAC in three actual samples (milk, green tea and orange juice). Furthermore, we prepared a rapid detection strip to meet the needs of practical application, making a positive contribution to food quality evaluation. • Au 2 Pt bimetallic nanozymes exhibited excellent peroxidase-like activity. • A nanozyme colorimetric sensor for detection of five antioxidants was constructed. • Pt atoms in the bimetallic nanozyme were active sites. • The evaluation of TAC in food was achieved by this bimetallic nanozyme sensor. • A rapid detection strip based on the bimetallic nanozyme was prepared. [ABSTRACT FROM AUTHOR]

The identification of sulfur-containing metal salts (SCMs) is of great interest because they play an important role in many biological processes and diseases. Here, we constructed a ternary channel colorimetric sensor array to detect multiple SCMs simultaneously, relying on monatomic Co embedded in nitrogen-doped graphene nanozyme (CoN 4 -G). Due to the unique structure, CoN 4 -G exhibits activity similar to native oxidases, capable of catalysing directly the oxidization of 3,3′,5,5′-tetramethylbenzidine (TMB) by O 2 molecules independent of H 2 O 2. Density functional theory (DFT) calculations suggest that CoN 4 -G has no potential barrier in the whole reaction route, thus presenting higher oxidase-like catalytic activity. Based on different degrees of TMB oxidation, different colorimetric response changes are obtained as "fingerprints" on the sensor array. The sensor array can discriminate different concentrations of unitary, binary, ternary, and quaternary SCMs and has been successfully applied to detect six real samples (soil, milk, red wine and egg white). To advance the field detection of the above four types of SCMs, we creatively propose a smartphone-based autonomous detection platform with a linear range of 1.6–320 μM and a limit of detection of 0.0778–0.218 μM, which demonstrates the potential use of sensor arrays in the application of disease diagnosis and food and environment monitoring. [Display omitted] • A simple and effective colorimetric sensor array was constructed based on CoN 4 -G. • The barrierless electron interaction led to the higher oxidase activity of CoN 4 -G. • The array could generate a fingerprint to identify various SCMs by LDA analysis. • The array gave low LODs for SCMs detection. • A smartphone-based APP was constructed to promote the on-site detection of SCMs. [ABSTRACT FROM AUTHOR]

Abstract The monobactam antibiotic, aztreonam, can be hydrolyzed by some β-lactamases (NDM-1), whereas other β-lactamases, including VIM-1, have no hydrolytic activity on aztreonam. NDM-1 and VIM-1 are both metallo-β-lactamases (MBLs), but they catalyze hydrolysis at different active site residues, which is reflected in their obvious activity difference with aztreonam. In this work, to explore the catalytic hydrolysis mechanism of MBLs at the atomic level, molecular dynamic simulations were performed for NDM-1-aztreonam and VIM-1-aztreonam complexes based on the molecular docking analysis. Molecular modeling revealed the binding of aztreonam to the active regions of NDM-1 and VIM-1. Residues Met67, Phe70, Asp124, Thr190, and His250 play key roles in the binding of aztreonam with NDM-1. His116, Asp118, Cys198, His201, and His240 are the critical residues for the binding of aztreonam with VIM-1. Interestingly, Asp124 displayed the strongest binding energy (ΔE total = −11.28 kcal/mol), which was nearly 10 times higher than that of the other residues in the NDM-1-aztreonam complex. A similar result was found for the binding of aztreonam with VIM-1, with Asp118 displaying the strongest binding energy (ΔE total = −2.95 kcal/mol). These results implicated aspartic acid as the critical active site in the catalytic hydrolysis pocket of NDM-1 and VIM-1. However, in the VIM-1-aztreonam complex, because of the strong π-π interaction between the thiazol ring group of aztreonam and the imidazole ring groups of His201 and His240, the binding energy obtained from Asp118 become significantly weaker than that of aztreonam with Asp124 of NDM-1. Analysis of the simulation trajectory indicated that the thiazol ring plane of aztreonam is almost parallel to the imidazole ring planes of His201 and His240, implying that they can form a strong π-π interaction, which is consistent with the above results. On the basis of the computational biology results, it was confirmed that aspartic acid in the active pocket of NDM-1 and VIM-1 can effectively promote substrate hydrolysis, while histidine on the other side of the active pocket can block the binding of the substrate with aspartic acid, leading to the loss of hydrolysis. Graphical abstract Unlabelled Image Highlights • The interaction of aztreonam towards the NDM-1 and VIM-1 complexes were explored. • The binding sites of aztreonam in the complexes were identified. • Aspartic acid in the active pocket of NDM-1 and VIM-1 promote substrate hydrolysis. • Histidine in the active pocket block the hydrolysis of the substrate. [ABSTRACT FROM AUTHOR]

Sortase B (SrtB) is a vital virulence factor that plays a critical role in Staphylococcus aureus (S. aureus) infections, indicating that it could be a latent target for S. aureus infections. In this study, phloretin, a natural compound that primarily exists in the pericarp and velamen of apples and pears, shows little anti-S. aureus activity, but significantly inhibited SrtB activity in vitro. The results of lactate dehydrogenase release and live/dead cell assays suggested that phloretin reduced human alveolar epithelial cell damage caused by S. aureus. Additionally, an adhesion assay confirmed that phloretin lowered the colony count of S. aureus in human alveolar cells. Phloretin treatment significantly attenuated the inflammatory response in macrophage cells (J774) co-cultured with S. aureus as determined by an enzyme-linked immune-sorbent assay. Furthermore, the results of molecular dynamics simulation, site-directed mutagenesis, and fluorescence spectroscopy quenching indicated that phloretin was directly located in the active pocket of SrtB and blocked substrate binding, leading to the loss of SrtB activity. These results indicate that phloretin is a possible candidate for treatment of S. aureus infections. [ABSTRACT FROM AUTHOR]

• Magnetic mesoporous carbon was loaded on the magnetic electrode to prepare a sensor. • The selectivity of aptamer-streptomycin controls the electrical signal of reaction. • Molecule modelling reveals that aptamer-streptomycin has the highest affinity. • The sensor exhibits the detection limit of 0.015 nM for streptomycin detection. Exploiting a simple and sensitive sensor to efficiently detect streptomycin (STR) in milk is critical for resolving the harm caused to humans by STR residues. This study reports an electrochemical sensor using magnetic mesoporous carbon materials (MMCM) as a loaded material through magnetic adsorption immobilized on magnetic glassy carbon electrode (MGCE) and adsorbing unlabeled streptomycin aptamer (STP) as the identification element. The sensor can detect STR sensitively with a wide detection range (0.172–17.2 × 103 and 17.2 × 103 –17.2 × 105 nM) and a low detection limit of 0.015 nM. Experimental results revealed that the specific binding of STP with STR on the electrode changed the configuration of STP, thereby causing current change of differential pulse voltammetry curve. Compared with HPLC, this study provides a new method for rapid and sensitive detection of STR in milk (n = 5, 95 % confidence level, RSD＜5%). [ABSTRACT FROM AUTHOR]

Fresh Tremella fuciformis is becoming more popular among consumers as an edible fungus, as it is more natural and nutritious than dried T. fuciformis. However, fresh T. fuciformis is susceptible to contamination by Burkholderia gladioli leading to deterioration in quality and safety. In this study, clove essential oil nanoemulsions (CNE) were prepared and then incorporated into chitosan coating (CSC) to develop a clove essential oil nanoemulsion/chitosan coating (CNE-CSC) for bacteriostatic and preservation of fresh T. fuciformis. The results showed that CNE-CSC significantly inhibited the growth of B. gladioli with the inhibition rate >85% when the concentration was 1.25 g/L and inhibited more than 85% of biofilm formation when the concentration was as low as 0.625 g/L. The inhibitory activity of CNE-CSC for the growth of B. gladioli directly lowered the expression of bongkrekic acid and then reduced the threat posed by bongkrekic acid to food safety. Moreover, in B. gladioli infection models, CNE-CSC treatment significantly prolonged the preservation of fresh T. fuciformis by preventing B. gladioli from infecting models. Therefore, CNE-CSC could be used as a safe, non-toxic, edible and new preservative coating for fresh T. fuciformis. • Clove essential nanoemulsion (CNE) was prepared. • CNE was incorporated into chitosan as antimicrobial coating (CNE-CSC). • CNE-CSC showed the high antibacterial activity against B. gladioli. • CNE-CSC extended the fresh T. fuciformis shelf-life to 9 days. • CNE-CSC improved the storage quality and safety of fresh T. fuciformis. [ABSTRACT FROM AUTHOR]

The images of cells under microscope in Figure 2 and Figure S2 were misused from Wang G et al. Front Cell Infect Microbiol. 2018 Nov 30;8:418. These images were generated in the same set of assays. [ABSTRACT FROM AUTHOR]

The critical role of sortase A in gram-positive bacterial pathogenicity makes this protein a good potential target for antimicrobial therapy. In this study, we report for the first time the crystal structure of Listeria monocytogenes sortase A and identify the active sites that mediate its transpeptidase activity. We also used a sortase A (SrtA) enzyme activity inhibition assay, simulation, and isothermal titration calorimetry analysis to discover that chalcone, an agent with little anti- L. monocytogenes activity, could significantly inhibit sortase A activity with an IC 50 of 28.41 ± 5.34 μM by occupying the active site of SrtA. The addition of chalcone to a co-culture of L. monocytogenes and Caco-2 cells significantly inhibited bacterial entry into the cells and L. monocytogenes -mediated cytotoxicity. Additionally, chalcone treatment decreased the mortality of infected mice, the bacterial burden in target organs, and the pathological damage to L. monocytogenes -infected mice. In conclusion, these findings suggest that chalcone is a promising candidate for the development of treatment against L. monocytogenes infection. [ABSTRACT FROM AUTHOR]

[Display omitted] Signal transducer and activator of transcription 3 (STAT3) has been proposed as a target for melanoma prevention. Luteolin, a bioactive flavonoid abundant in medicinal herbs, has been reported to have anti-melanoma activity in vitro. However, its in vivo anti-melanoma effects and underlying mechanisms have not been fully elucidated. In this study, ten cell lines and two mouse models (B16F10 allograft and A375 xenograft models) were used for assessing the in vitro and in vivo anti-melanoma effects of luteolin. A STAT3 over-activated stable A375 cell line was used to determine the contribution of STAT3 signaling in luteolin's anti-melanoma effects. Results showed that luteolin dose-dependently reduced viability of melanoma cells. Luteolin also induced apoptosis in, and suppressed migration and invasion of, A375 and B16F10 melanoma cells. Mechanistically, luteolin inhibited phosphorylation of STAT3 and Src (an upstream kinase of STAT3), accelerated ubiquitin–proteasome pathway-mediated STAT3 degradation, and downregulated the expression of STAT3-targeted genes involved in cell survival and invasion in melanoma cells. Molecular modelling and surface plasmon resonance imaging showed that luteolin stably bound to the protein kinase domain of Src. Animal studies demonstrated that prophylactic administration of luteolin restrained melanoma growth and Src/STAT3 signaling in both A375 and B16F10 melanoma-bearing mice. Moreover, luteolin's anti-melanoma effects were diminished by STAT3 over-activation in A375 cells. Our findings indicate that luteolin inhibits STAT3 signaling by suppressing STAT3 activation and promoting STAT3 protein degradation in melanoma cells, thereby exhibiting anti-melanoma effects. This study provides further pharmacological groundwork for developing luteolin as a chemopreventive agent against melanoma. [ABSTRACT FROM AUTHOR]

α-Hemolysin (α-HL) is a self-assembling, channel-forming toxin that is produced as a soluble monomer by Staphylococcus aureus strains. Until now, α-HL has been a significant virulence target for the treatment of S. aureus infection. In our previous report, we demonstrated that some natural compounds could bind to α-HL. Due to the binding of those compounds, the conformational transition of α-HL from the monomer to the oligomer was blocked, which resulted in inhibition of the hemolytic activity of α-HL. However, these results have not indicated how the binding of the α-HL inhibitors influence the conformational transition of the whole protein during the oligomerization process. In this study, we found that three natural compounds, Oroxylin A 7-O-glucuronide (OLG), Oroxin A (ORA), and Oroxin B (ORB), when inhibiting the hemolytic activity of α-HL, could bind to the “stem” region of α-HL. This was completed using conventional Molecular Dynamics (MD) simulations. By interacting with the novel binding sites of α-HL, the ligands could form strong interactions with both sides of the binding cavity. The results of the principal component analysis (PCA) indicated that because of the inhibitors that bind to the “stem” region of α-HL, the conformational transition of α-HL from the monomer to the oligomer was restricted. This caused the inhibition of the hemolytic activity of α-HL. This novel inhibition mechanism has been confirmed by both the steered MD simulations and the experimental data obtained from a deoxycholate-induced oligomerization assay. This study can facilitate the design of new antibacterial drugs against S. aureus. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a common human pathogenic bacteria that can cause serious infections, including lethal staphylococcal pneumonia. The development of antimicrobial resistance has limited treatment options for this pathogen; consequently, novel antibiotics and strategies are urgently desired to combat these infections. In recent years, virulence factors secreted by pathogenic microorganisms have been developed as targets for drug discovery. Alpha-hemolysin, a pore-forming cytotoxin that is secreted by most S. aureus strains, is essential for the pathogenesis of S. aureus pneumonia. In this study, we report that apigenin, a compound extracted from parsley that has no antimicrobial activity vs. S. aureus in vitro, can remarkably decrease the production of α-hemolysin at low concentrations. When added to the A549 cells and S. aureus co-culture system, apigenin protected A549 cells from α-hemolysin-mediated injury. Furthermore, in vivo tests indicated that apigenin alleviated injury of the lung tissue and decreased cytokine levels in the bronchoalveolar lavage fluid in the mouse model of S. aureus pneumonia. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we present the release of baicalin from hexagonal periodic mesoporous silica SBA-15 and amino-functionalized mesoporous SBA-15 (A-SBA-15), which serve as drug delivery systems (SBA-15/baicalin and A-SBA-15/baicalin). The modified and drug loaded mesoporous materials were characterized by XRD, SEM, TEM, N2 physisorption, IR, TG and HPLC. The results demonstrated that slightly higher amount of baicalin was loaded in APS-SBA-15, and the dissolution rate of baicalin from the A-SBA-15/baicalin was much faster than from the SBA-15/baicalin. A-SBA-15/baicalin as baicalin delivery system was better than SBA-15/baicalin because the faster dissolution rate compared with SBA-15/baicalin was more conducive to drug absorption. [Copyright &y& Elsevier]

S taphylococcus aureus is a versatile pathogen that can cause life-threatening infections. The growing emergence of methicillin-resistant S . aureus strains and a decrease in the discovery of new antibiotics warrant the search for new therapeutic targets to combat infections. S taphylococcus aureus produces many extracellular virulence factors that contribute to its pathogenicity. Therefore, targeting bacterial virulence as an alternative strategy to the development of new antimicrobials has gained great interest. α-Toxin is a 33.2-k Da, water-soluble, pore-forming toxin that is secreted by most S . aureus strains. α-Toxin is essential for the pathogenesis of pneumonia, as strains lacking α-toxin display a profound defect in virulence. In this report, we demonstrate that isoalantolactone ( IAL), a naturally occurring compound found in I nula helenium ( Compositae), has no anti- S . aureus activity as per MIC evaluation in vitro. However, IAL can markedly inhibit the expression of α-toxin in S . aureus at very low concentrations. Furthermore, the in vivo data indicate that treatment with IAL protects mice from S . aureus pneumonia. [ABSTRACT FROM AUTHOR]

Image, graphical abstract The eukaryotic-like serine/threonine phosphatase (Stp1) is an enzyme-dependent protein phosphatase involved in regulating various virulence factors of Staphylococcus aureus. Owing to its role in S. aureus infections, Stp1 has become a potential target for antibiotic development. Unfortunately, there are very few reports describing Stp1 inhibitors. Using virtual screening, we have identified a potent and effective Stp1 inhibitor, verbascoside (VBS). Interestingly, the kinetics of the enzymatic reaction revealed that this natural inhibitor acts via both competitive and allosteric mechanisms. To explore the mechanism of interaction between VBS and Stp1, standard molecular dynamics (MD) simulations were performed for the Stp1-VBS complex. Consistent with the experimental results, competitive and allosteric binding sites for VBS were identified in Stp1. Met39, Gly41, His42, Arg161, and Asn162 residues were involved in the competitive binding of VBS, while Arg122, Ser136, Asp137, Asn142, and Val145 residues were associated with the allosteric binding of VBS. The contributions of these residues were confirmed by amino acid site-directed mutagenesis and fluorescence quenching experiments. This work demonstrates that VBS is a potent anti-virulence compound against S. aureus infection, laying the foundation for the further development of novel anti-virulence agents. [ABSTRACT FROM AUTHOR]

Abstract: The bimodal porous structured mesporous bioactive glass (MBG) materials consisting of macropores were prepared using the natural Mediterranean sea sponge as macropored hard templates and P123 as mesopore soft templates, respectively. The macroporous structures of the natural Mediterranean sea sponge as macropored were replicated with the walls containing highly ordered MBG as well. Dexamethasone (DEX) was employed as a model drug and the release profiles showed that the dual porous materials had a sustained drug delivery capability. In addition, the materials had higher ability to induce hydroxycarbonate apatite (HAp) formation. Therefore, such highly ordered dual pore MBG materials might be used as a bioactive drug release system for preparation of bone implant materials. [Copyright &y& Elsevier]

New Delhi metallo-β-lactamase (NDM-1), one of the metallo-β-lactamases (MBLs), leads to antibiotic resistance in clinical treatments due to the strong ability of hydrolysis to almost all kinds of β-lactam antibiotics. Therefore, there is the urgent need for the research and development of the novel drug-resistant inhibitors targeting NDM-1. In this study, ZINC05683641 was screened as potential NDM-1 inhibitor by virtual screening and the inhibitor mechanism of this compound was explored based on molecular dynamics simulation. The nitrocefin assay showed that the IC50 value of ZINC05683641 was 13.59 ± 0.52 μM, indicating that the hydrolytic activity of NDM-1 can be obviously suppressed by ZINC05683641. Further, the binding mode of ZINC05683641 with NDM-1 was obtained by molecular modeling, binding free energy calculation, mutagenesis assays and fluorescence-quenching assays. As results, ILE-35, MET-67, VAL-73, TRP-93, CYS-208, ASN-220 and HIS-250 played the key roles in the binding of NDM-1 with ZINC05683641. Interestingly, these key residues were exactly located in the catalytic activity region of NDM-1, implying that the inhibitor mechanism of ZINC05683641 against NDM-1 was the competitive inhibition. These findings will provide an available approach to research and develop new drug against NDM-1 and treatment for bacterial resistance. [ABSTRACT FROM AUTHOR]