Unique coumarin aminophosphonates as new antibacterial agents were designed and synthesized to combat severely bacterial resistance. Bioactivity assessment identified that 3-hydroxylphenyl ...aminophosphonate 6f with low hemolytic activity not only exhibited excellent inhibition potency against Staphylococcus aureus at low concentration (0.5 μg/mL) in vitro but also showed considerable antibacterial potency in vivo. Meanwhile, the active compound 6f was capable of eradicating the S. aureus biofilm, thus alleviating the development of S. aureus resistance. Furthermore, the drug combination of compound 6f with norfloxacin could enhance the antibacterial efficacy. Mechanistic explorations manifested that molecule 6f was able to destroy the integrity of cell membrane, which resulted in the leakage of protein and metabolism inhibition. The cellular redox homeostasis was interfered through inducing the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), leading to the reduction of glutathione (GSH) activity and lipid peroxidation. Furthermore, compound 6f could intercalate into DNA base pair to hinder normal biological function. The above results provided powerful information for the further development of coumarin aminophosphonates as antibacterial agents.
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•Unique coumarin aminophosphonates with potent antibacterial efficacy were developed.•Molecule 6f exerted low toxicity, no obvious resistance and good bioavailability.•Compound 6f could disturb the membrane integrity and lead to the leakage of intracellular materials.•Compound 6f could induce oxidative damage and restrain metabolism.
Unique coumarin conjugates with thiazolidinone as novel structural antibacterial modulators were exploited to combat the lethal multidrug-resistant bacterial infections. Bioactivity evaluation ...identified that indole-incorporated coumarin thiazolidinone conjugate 14a with low cytotoxicity to mammalian cells showed a broad antibacterial spectrum and exerted potent inhibition efficiencies to the tested germs at low concentrations (0.25–2 μg/mL). Moreover, the favorable performance of 14a in eradicating bacterial biofilm was beneficial to avert developing drug resistance. Mechanistic explorations revealed that molecule 14a was able to destroy cell membrane, leading to the leakage of intracellular materials and metabolism inhibition. The accumulation of excess reactive oxygen species (ROS) mediated by compound 14a could impede glutathione (GSH) activity and induce lipid peroxidation to suppress bacteria growth. Furthermore, compound 14a could not only intercalate into DNA base pair but also take part in non-covalent interaction with DNA gyrase B to hinder their biological function. Quantum chemical study indicated that molecule 14a had low HOMO-LUMO energy gap, which resulted in more stabilizing interactions and was conducive to displaying better antibacterial activity. ADMET analysis manifested that 14a possessed promising pharmacokinetic properties.
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•Novel thiazolidinone-conjugated coumarins with broad antibacterial spectrum were developed.•Compound 14a performed better inhibition efficacy than norfloxacin.•Molecule 14a exerted low toxicity, no obvious resistance and good bioavailability.•Compound 14a could disturb the membrane integrity and lead to the leakage of intracellular materials.•Compound 14a could restrain metabolism and induce oxidative damage.
In this work, a high thermoelectric figure of merit, zT of 1.9 at 740 K is achieved in Ge
Bi
Te crystals through the concurrent of Seebeck coefficient enhancement and thermal conductivity reduction ...with Bi dopants. The substitution of Bi for Ge not only compensates the superfluous hole carriers in pristine GeTe but also shifts the Fermi level (E
) to an eligible region. Experimentally, with moderate 6-10% Bi dopants, the carrier concentration is drastically decreased from 8.7 × 10
cm
to 3-5 × 10
cm
and the Seebeck coefficient is boosted three times to 75 μVK
. In the meantime, based on the density functional theory (DFT) calculation, the Fermi level E
starts to intersect with the pudding mold band at L point, where the band effective mass is enhanced. The enhanced Seebeck coefficient effectively compensates the decrease of electrical conductivity and thus successfully maintain the power factor as large as or even superior than that of the pristine GeTe. In addition, the Bi doping significantly reduces both thermal conductivities of carriers and lattices to an extremely low limit of 1.57 W m
K
at 740 K with 10% Bi dopants, which is an about 63% reduction as compared with that of pristine GeTe. The elevated figure of merit observed in Ge
Bi
Te specimens is therefore realized by synergistically optimizing the power factor and downgrading the thermal conductivity of alloying effect and lattice anharmonicity caused by Bi doping.
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•Coumarin thiazoles with novel broad antimicrobial spectrum were developed.•Compound V-a exerted potent inhibition efficacy towards MRSA (MIC = 1 μg/mL).•Compound V-a showed low ...toxicity, no obvious resistance and good bioavailability.•Compound V-a could effectively damage the membrane and lead to the leakage of protein.•Derivative V-a could induce the generation of ROS.
A novel type of coumarin thiazoles as unique multi-targeting antimicrobial agents were developed through four steps including cyclization, nucleophilic substitution and condensation starting from commercial resorcine. Most of the prepared coumarin thiazoles displayed favorable inhibitory potency against the tested strains. Noticeably, methyl oxime V-a exerted potent inhibitory efficacy against methicillin-resistant Staphylococcus aureus (MRSA) at low concentration (1 μg/mL) and showed broad antimicrobial spectrum. Medicinal bioevaluations revealed that the active molecule V-a exhibited low toxicity toward mammalian cells, rapidly killing effect, good capability of eradicating MRSA biofilms and unobvious probability to engender drug resistance. Chemical biological methods were employed to investigate preliminary mechanism, which indicated that compound V-a was able to damage the integrity of membrane to trigger leakage of protein, insert into MRSA DNA to block its replication and induce the generation of reactive oxygen species (ROS) to inhibit bacterial growth. Computational study manifested that low HOMO-LUMO energy gap of molecule V-a was favorable to exert high antimicrobial activity.
The number of confirmed COVID-19 cases has increased drastically; however, information regarding the impact of this disease on the occurrence of arrhythmias is scarce. The aim of this study was to ...determine the impact of COVID-19 on arrhythmia occurrence. This prospective study included patients with COVID-19 treated at the Leishenshan Temporary Hospital of Wuhan City, China, from February 24 to April 5, 2020. Demographic, comorbidity, and arrhythmias data were collected from patients with COVID-19 (n = 84) and compared with control data from patients with bacterial pneumonia (n = 84) infection. Furthermore, comparisons were made between patients with severe and nonsevere COVID-19 and between older and younger patients. Compared with patients with bacterial pneumonia, those with COVID-19 had higher total, mean, and minimum heart rates (all P<0.01). Patients with severe COVID-19 (severe and critical type diseases) developed more atrial arrhythmias compared with those with nonsevere symptoms. Plasma creatine kinase isoenzyme (CKMB) levels (P=0.01) were higher in the severe group than in the nonsevere group, and there were more deaths in the severe group than in the nonsevere group (6 (15%) vs. 3 (2.30%); P=0.05). Premature atrial contractions (PAC) and nonsustained atrial tachycardia (NSAT) were significantly positively correlated with plasma CKMB levels but not with high-sensitive cardiac troponin I or myoglobin levels. Our data demonstrate that COVID-19 patients have higher total, mean, and minimum heart rates compared with those with bacterial pneumonia. Patients with severe or critical disease had more frequent atrial arrhythmias (including PAC and AF) and higher CKMB levels and mortality than those with nonsevere symptoms.
Rifampicin resistance (Rif
) mutations in the RNA polymerase β subunit (
) gene exhibit pleiotropic phenotypes as a result of their effects on the transcription machinery in prokaryotes. However, the ...differences in the effects of the mutations on the physiology and metabolism of the bacteria remain unknown. In this study, we isolated seven Rif
mutations in
, including six single point mutations (H485Y, H485C, H485D, H485R, Q472R, and S490L) and one double point mutation (S490L/S617F) from vegetative cells of an endophytic strain,
CC09. Compared to the wild-type (WT) strain (CC09), the H485R and H485D mutants exhibited a higher degree of inhibition of
spore germination, while the H485Y, S490L, Q472R, and S490L/S617F mutants exhibited a lower degree of inhibition due to their lower production of the antibiotic iturin A. These mutants all exhibited defective phenotypes in terms of pellicle formation, sporulation, and swarming motility. A hierarchical clustering analysis of the observed phenotypes indicated that the four mutations involving amino acid substitutions at H485 in RpoB belonged to the same cluster. In contrast, the S490L and Q472R mutations, as well as the WT strain, were in another cluster, indicating a functional connection between the mutations in
and phenotypic changes. Our data suggest that Rif
mutations cannot only be used to study transcriptional regulation mechanisms, but can also serve as a tool to increase the production of bioactive metabolites in
.
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•Bi-doped rGO/Co3O4 nanohybrids were obtained by one-pot synthesis method.•Very high response value of 150 and good selectivity towards 100 ppm ethanol at low temperature of 120 ...°C.•The content of Bi dopant has significant effect on the sensitivity and optimum working temperature.
Gas sensors based on metal oxide semiconductors (MOSCs) and reduced graphene oxide (rGO) for sensing of organic volatile compounds often suffer from high operation temperature, low responses, poor selectivity, or narrow detection range. Herein, we design and fabricate Bi-doped rGO/Co3O4 (BGCO) nanohybrids with a flower morphology, which have been applied as a sensing layer for an ethanol sensor. This BGCO sensor exhibits a maximum p-type response of 178.1 towards 500 ppm ethanol at an optimum working temperature of 120 °C. The sensor’s detection range for the ethanol concentration is from 500 ppb to 500 ppm, and the sensor has an excellent selectivity to ethanol compared to other types of organic volatile gases and oxidizing gas such as NO2. The enhanced ethanol sensing mechanism is attributed to the increased conductivity of Bi doped rGO/Co3O4 material. Additionally, incorporation of Bi dopant can promote the redox reaction, and the rGO/Co3O4 act as the catalyst.
In this work, a new neutron and γ （n/γ） discrimination method based on an Elman Neural Network （ENN） is proposed to improve the discrimination performance of liquid scintillator （LS） detectors. ...Neutron and γ data were acquired from an EJ-335 LS detector, which was exposed in a 241Am-9Be radiation field. Neutron and γ events were discriminated using two methods of artificial neural network including the ENN and a typical Back Propagation Neural Network （BPNN） as a control. The results show that the two methods have different n/γ discrimination performances. Compared to the BPNN, the ENN provides an improved of Figure of Merit （FOM） in n/γ discrimination. The FOM increases from 0.907 4- 0.034 to 0.953 4- 0.037 by using the new method of the ENN. The proposed n/γdiscrimination method based on ENN provides a new choice of pulse shape discrimination in neutron detection.
We demonstrate experimentally an atomic magnetometer based on optical pumping theory, a magnetic resonance that is induced by a radio frequency field and dependent on the magnetic field strength. ...Compared with the conventional method using one radiation field, which is used not only as the probe beam but also as a pump beam, the additional re-pump beam can increase remarkably the amplitude of the signal. It is shown that the amplitude of the magnetic field resonance signal can increase more than 55% by using an additional re-pump beam, which makes the sensitivity of the magnetometer higher. Finally, we investigate the relation between amplitude of the signal and re-pump laser power, and calculate the atomic population in the trapping states with rate equations.
A dressed-state perturbation theory beyond the rotating wave approximation （RWA） is presented to investigate the interaction between a two-level electronic transition of polar molecules and a ...quantized cavity field. Analytical expressions can be explicitly derived for both the ground- and excited-state-energy spectrums and wave functions of the system, where the contribution of permanent dipole moments （PDM） and the counter-rotating wave term （CRT） can be shown separately. The validity of these explicit results is discussed by comparison with the direct numerical simulation. Compared to the CRT coupling, PDM results in the coupling of more dressed states and the energy shift is proportional to the square of the normalized permanent dipole difference, and a greater Bloch-Siegert shift can be produced in the giant dipole molecule cavity QED. In addition, our method can also be extended to the solution of the two-level atom Rabi model Hamiltonian beyond the RWA.
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