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Super bacterial infection caused by metallo‐β‐lactamases (MβLs) has posed a serious public health threat, while developing inhibitors of MβLs is an ideal strategy to combat drug‐resistance. Here, seventeen sulfonylureas were synthesized and confirmed. Biological assay shown that these molecules effectively inhibited MβL ImiS, with an IC50 value in the range of 29.5–188.2 μM, and the best inhibitor competitively and irreversibly inhibited ImiS with a Ki value of 15.2 μM. Structure‐activity relationship analysis revealed that the chlorine‐substituted phenyl significantly raised inhibitory activity of sulfonylureas on ImiS. Antibacterial and chessboard dilution assays shown that the most sulfonylureas tested enhanced antimicrobial effect of meropenem (MER) on E. coli‐ImiS, and the two inhibitors with best effect resulted in an 8‐fold reduction in MIC of MER. Mice tests shown that the best inhibitor synergizing MER virtually diminished the load of E. coli‐ImiS in spleen and liver. Docking study revealed that the sulfonylurea reacts with ImiS mainly through the sulfonyl group, in which one of oxygen atoms coordinates to Zn(II), and forms two hydrogen bonds with Lys224 (2.1 Å) and His263 (3.1 Å). This work revealed the sulfonylureas are promising candidates for the development of ImiS inhibitors. [ABSTRACT FROM AUTHOR]

The metallo‐β‐lactamases (MβLs) produced by pathogens has issued a challenge to the treatment of bacterial infections worldwide. A number of oxazolethioacetamides were designed and synthesized as potential MβLs inhibitors. Most of the compounds displayed inhibitory activity against MβL L1 with an IC50 value range of 0.19–0.38 μM. The fluorine substituted compounds also inhibited VIM‐2 with IC50 value of 2.1 to 6.8 μM. Molecule Docking showed the style and position of electron withdrawing groups played important role between the oxazolethioacetamides and MβLs. [ABSTRACT FROM AUTHOR]

Multidrug-resistant bacterial infections mediated by metallo-β-lactamases (MβLs) have grown into an emergent health threat, and development of novel antimicrobials is an ideal strategy to combat the infections. Herein, a novel vancomycin derivative Vb was constructed by conjugation of triazolylthioacetamide and vancomycin molecules, characterized by reverse-phase high performance liquid chromatography (HPLC) and confirmed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The biological assays revealed that Vb effectively inhibited S. aureus and methicillin-resistant S. aureus (MRSA), gradually increased the antimicrobial effect of β-lactam antibiotics (cefazolin, meropenem and penicillin G) and exhibited a dose-dependent synergistic antibacterial effect against eight resistant strains tested, which was confirmed by the time-kill curves determination. Most importantly, Vb increased the antimicrobial effect of meropenem against the clinical isolates EC08 and EC10 and E. coli producing ImiS and CcrA, resulting in a 4- and 8-fold reduction in MIC values, respectively, at a dose up to 32 μg/mL. This work offers a promising scaffold for the development of MβLs inhibitors, specifically antimicrobials for clinically drug-resistant isolates. [ABSTRACT FROM AUTHOR]

GFP‐like chromoproteins (CPs) with non‐fluorescence ability have been used as bioimaging probes. Existing CPs have voids in the optical absorption window which limits their extensibility. The development of new CP color is therefore ongoing. Here, we cloned CPs from the jellyfish, Olindias formosa, and developed a completely non‐fluorescent monomeric red CP, R‐Velour, with an absorption peak at 528 nm. To analyze the photophysical properties from a structural aspect, we determined the crystal structure of R‐Velour at a 2.1 Å resolution. R‐Velour has a trans‐chromophore similar to the green fluorescence protein, Gamillus, derived from the same jellyfish. However, in contrast to the two coplanar chromophoric rings in Gamillus, R‐Velour has a large torsion inducing non‐fluorescence property. Through site‐directed mutagenesis, we surveyed residues surrounding the chromophore and found a key residue, Ser155, which contributes to the generation of four‐color variants with the bathochromic and hypsochromic shift of the absorption peak, ranging from 506 to 554 nm. The recently proposed spectrum shift theory, based on the Marcus–Hush model, supports the spectrum shift of these mutants. These findings may support further development of R‐Velour variants with useful absorption characteristics for bioimaging, including fluorescence lifetime imaging and photoacoustic imaging. [ABSTRACT FROM AUTHOR]

In this paper, the macroscopic quantum entanglement and squeezing in an unresolved‐sideband atom‐optomechanical system with a modulated optical parametric amplifier (OPA) inside the cavity are studied. Increasing the parametric gain of the OPA, the quantum‐classical correspondence between the atom‐mirror entanglement and classical nonlinear dynamics can be found. The critical point where the system experiences the transition from periodic oscillation to period‐doubling motion can be characterized by the singularity of the atom–mirror entanglement. Furthermore, the dependence of the atom–mirror entanglement and mechanical squeezing on the detuning and the parametric gain of the OPA as well as the environment temperature are investigated in detail. It is found that the atom‐mirror entanglement can be enhanced and the mechanical squeezing can be generated by modulating the OPA. [ABSTRACT FROM AUTHOR]

Compared with traditional crystalline materials, amorphous alloys have excellent corrosion and wear resistance and high elastic modulus, due to their unique short-range ordered and long-range disordered atomic arrangement as well as absence of defects, such as grain boundaries and dislocations. Owing to the limitation of the bulk size of amorphous alloys as structural materials, the application as functional coatings can widely extend their use in various engineering fields. This review first briefly introduces the problems involved during high temperature preparation processes of amorphous coatings, including laser cladding and thermal spraying. Cold spray (CS) is characterized by a low-temperature solid-state deposition, and thus the oxidation and crystallization related with a high temperature environment can be avoided during the formation of coatings. Therefore, CS has unique advantages in the preparation of fully amorphous alloy coatings. The research status of Fe-, Al-, Ni-, and Zr-based amorphous alloy coatings and amorphous composite coatings are reviewed. The influence of CS process parameters, and powders and substrate conditions on the microstructure, hardness, as well as wear and corrosion resistance of amorphous coatings is analyzed. Meanwhile, the deposition mechanism of amorphous alloy coatings is discussed by simulation and experiment. Finally, the key issues involved in the preparation of amorphous alloy coatings via CS technology are summarized, and the future development is also being prospected. [ABSTRACT FROM AUTHOR]

[Display omitted] • DpC was identified to be broad-spectrum inhibitor of metallo-β-lactamases. • DpC competitively and reversibly inhibited NDM-1. • The inhibitor cooperated with meropenem to kill bacteria producing MβLs. To combat the superbug infection caused by metallo-β-lactamases (MβLs), a dipyridyl-substituted thiosemicarbazone (DpC), was identified to be the broad-spectrum inhibitor of MβLs (NDM-1, VIM-2, IMP-1, ImiS, L1), with an IC 50 value in the range of 0.021–1.08 µM. It reversibly and competitively inhibited NDM-1 with a K i value of 10.2 nM. DpC showed broad-spectrum antibacterial effect on clinical isolate K. pneumonia , CRE, VRE, CRPA and MRSA, with MIC value ranged from 16 to 32 µg/mL, and exhibited synergistic antibacterial effect with meropenem on MβLs-producing bacteria, resulting in a 2–16-, 2–8-, and 8-fold reduction in MIC of meropenem against EC-MβLs, EC01-EC24, K. pneumonia , respectively. Moreover, mice experiments showed that DpC also had synergistic antibacterial action with meropenem. In this work, DpC was identified to be a potent scaffold for the development of broad-spectrum inhibitors of MβLs. [ABSTRACT FROM AUTHOR]

Abstract Al-based metal matrix composite (Al-MMC) coatings were produced on AZ91 magnesium alloy substrates utilizing two distinct coating techniques, i.e. cold spraying (CS) and detonation thermal spraying (DS), and the microstructure, hardness, bonding strength and corrosion behaviour were comparatively studied. The results showed that the CS process, which was featured with high kinetic and low thermal input energies, led to the dense structure resulted from the high velocity impact of particles at the solid state. The DS processed coatings showed relatively high porosity owing to the melting and oxidation involved during the deposition. But, due to the high fraction of metallurgical bonding of deposited splats, the DS coating demonstrated superior mechanical properties in terms of hardness and bonding strength when the porosity was reduced at higher volume fraction of the ceramic reinforcement. With increasing the volume fraction of ceramic particles in the source powder, the transitional fracture from the adhesive to cohesive mode was observed for both CS and DS processed composite coatings. In addition, compared to the AZ91 alloy substrate, both CS and DS composite coatings showed improved corrosion resistance. Graphical abstract Unlabelled Image Highlights • The high kinetic energy and solid state deposition produced highly dense coatings. • Higher hardness & bonding strength obtained in DS with higher metallurgical bonding. • Transitional shear-failure from adhesive to cohesive associated with ceramic content. [ABSTRACT FROM AUTHOR]

Spherical Ba 0.96 La 0.04 TiO 3 powders were synthesized by a wet chemical method-based on a precipitation process, able of controlling uniformity and particle size. After sintering, fine-grain Ba 0.96 La 0.04 TiO 3 ceramics with good dielectric properties were obtained. Different synthesis routes of Ba 0.96 La 0.04 TiO 3 ceramics were used, and their effects on microstructure and dielectric properties were examined. Results showed that the ceramics samples prepared by La 3+ and Ba 2+ added together (abbreviated as, BLT-T) resulted in a mixture of large and small grains, sharp permittivity peaks, and high dielectrics loss. By comparison, another ceramics samples prepared by La 3+ and Ba 2+ added separately (BLT-S) exhibited uniform grain size and broadened/flattened permittivity peaks. The high value of ε r (3255) and low tan δ (0.01) at room temperature and negligible temperature coefficient of capacitance from − 35 to 85 °C suggested the suitability of the above materials for multilayer capacitor applications. [ABSTRACT FROM AUTHOR]

The main protease (M pro ) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) represents a promising target for antiviral drugs aimed at combating COVID-19. Consequently, the development of M pro inhibitor is an ideal strategy for combating the virus. In this study, we identified twenty-two dithiocarbamates (1 a-h), dithiocarbamate-Cu(II) complexes (2 a-hCu) and disulfide derivatives (2 a-e, 2 i) as potent inhibitors of M pro , with IC 50 value range of 0.09-0.72, 0.9-24.7, and 15.1-111 μM, respectively, through FRET screening. The enzyme kinetics, inhibition mode, jump dilution, and DTT assay revealed that 1 g may be a partial reversible inhibitor, while 2 d and 2 f-Cu are the irreversible and dose- and time-dependent inhibitors, potentially covalently binding to the target. Binding of 2 d, 2 f-Cu, and 1 g to M pro was found to decrease the stability of the protein. Additionally, DTT assays and thermal shift assays indicated that 2 f-Cu and 2 d are the nonspecific and promiscuous cysteine protease inhibitor. ICP-MS implied that the inhibitory activity of 2 f-Cu may stem from the uptake of Cu(II) by the enzyme. Cytotoxicity assays demonstrated that 2 d and 1 g exhibit low cytotoxicity, whereas 2 f-Cu show certain cytotoxicity in L929 cells. Overall, this work presents two promising scaffolds for the development of M pro inhibitors to combat COVID-19., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

A simple protocol for the noble-metal-free oxidative cyclization of enamines and t BuONO has been developed. This KI-mediated formal [4 + 1] cycloamination reaction provides a practical strategy for the synthesis of imidazole-4-carboxylic derivatives using t BuONO both as an aminating reagent and oxidant. The reaction features wide substrate scope and good functional tolerance for enamine compounds, even the unactivated ones.

GFP-like chromoproteins (CPs) with non-fluorescence ability have been used as bioimaging probes. Existing CPs have voids in the optical absorption window which limits their extensibility. The development of new CP color is therefore ongoing. Here, we cloned CPs from the jellyfish, Olindias formosa, and developed a completely non-fluorescent monomeric red CP, R-Velour, with an absorption peak at 528 nm. To analyze the photophysical properties from a structural aspect, we determined the crystal structure of R-Velour at a 2.1 Å resolution. R-Velour has a trans-chromophore similar to the green fluorescence protein, Gamillus, derived from the same jellyfish. However, in contrast to the two coplanar chromophoric rings in Gamillus, R-Velour has a large torsion inducing non-fluorescence property. Through site-directed mutagenesis, we surveyed residues surrounding the chromophore and found a key residue, Ser155, which contributes to the generation of four-color variants with the bathochromic and hypsochromic shift of the absorption peak, ranging from 506 to 554 nm. The recently proposed spectrum shift theory, based on the Marcus-Hush model, supports the spectrum shift of these mutants. These findings may support further development of R-Velour variants with useful absorption characteristics for bioimaging, including fluorescence lifetime imaging and photoacoustic imaging., (© 2022 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

The metallo-β-lactamases (MβLs) cleave the β-lactam ring of β-lactam antibiotics, conferring resistance against these drugs to bacteria. Twenty-four triazolylthioacetamides were prepared and evaluated as inhibitors of representatives of the three subclasses of MβLs. All these compounds exhibited specific inhibitory activity against NDM-1 with an IC50 value range of 0.15-1.90 μM, but no activity against CcrA, ImiS, and L1 at inhibitor concentrations of up to 10 μM. Compounds 4d and 6c are partially mixed inhibitors with K i values of 0.49 and 0.63 μM using cefazolin as the substrate. Structure-activity relationship studies reveal that replacement of hydrogen on the aromatic ring by chlorine, heteroatoms, or alkyl groups can affect bioactivity, while leaving the aromatic ring of the triazolylthiols unmodified maintains the inhibitory potency. Docking studies reveal that the typical potent inhibitors of NDM-1, 4d and 6c, form stable interactions in the active site of NDM-1, with the triazole bridging Zn1 and Zn2, and the amide interacting with Lys 211 (Lys224).