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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]

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]

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]

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]

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]

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 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]

[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]

[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]

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]

• 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]

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]

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]

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]

• Molecular modeling and binding free energy calculations were used. • Met39, Ile163, Ile164, Val167 and Asp233 were key residues in the complexes. • The structure-activity relation at the atomic level was determined. Ser/thr phosphatase Stp1 is an important virulence factor for Staphylococcus aureus (S. aureus) and plays a key role in its infectivity, suggesting that it could serve as a potential target for treatment of S. aureus infection. Previous studies found that the activity of Stp1 was inhibited by MDSA and its derivatives. In this paper, we used molecular docking, molecular modeling, molecular dynamics simulations, binding free energy decomposition calculations, and hydrogen bond analyses to explore the structure-activity relationship. Energy decomposition indicated that MDSA, hydroxymethyl MDSA, carboxymethyl MDSA and methyl MDSA can bind to the catalytic pocket of Stp1. Furthermore, Met39, Ile163, Ile164, Val167, Gly195 and Asp233 were key residues in the Stp1-inhibitor complexes. Due to the lack of a double salicylate structure, salicylic acid cannot bind to the active site of Stpl, leading to loss of inhibitory activity. Based on these results, the structure-activity relationship at the atomic level was determined, which can promote the development of new and more effective anti-drug resistance inhibitors. [ABSTRACT FROM AUTHOR]