3-O-Substituted Quercetin: an Antibiotic-Potentiating Agent against Multidrug-Resistant Gram-Negative Enterobacteriaceae through Simultaneous Inhibition of Efflux Pump and Broad-Spectrum Carbapenemases.

The discovery of safe and efficient inhibitors against efflux pumps as well as metallo-ß-lactamases (MBL) is one of the main challenges in the development of multidrug-resistant (MDR) reversal agents which can be utilized in the treatment of carbapenem-resistant Gram-negative bacteria. In this study, we have identified that introduction of an ethylene-linked sterically demanding group at the 3-OH position of the previously reported MDR reversal agent di-F-Q endows the resulting compounds with hereto unknown multitarget inhibitory activity against both efflux pumps and broad-spectrum ß-lactamases including difficult-to-inhibit MBLs. A molecular docking study of the multitarget inhibitors against efflux pump, as well as various classes of ß-lactamases, revealed that the 3-O-alkyl substituents occupy the novel binding sites in efflux pumps as well as carbapenemases. Not surprisingly, the multitarget inhibitors rescued the antibiotic activity of a carbapenem antibiotic, meropenem (MEM), in NDM-1 (New Delhi Metallo-ß-lactamase-1)-producing carbapenem-resistant Enterobacteriaceae (CRE), and they reduced MICs of MEM more than four-fold (synergistic effect) in 8-9 out of 14 clinical strains. The antibiotic-potentiating activity of the multitarget inhibitors was also demonstrated in CRE-infected mouse model. Taken together, these results suggest that combining inhibitory activity against two critical targets in MDR Gram-negative bacteria, efflux pumps, and ß-lactamases, in one molecule is possible, and the multitarget inhibitors may provide new avenues for the discovery of safe and efficient MDR reversal agents.

Potentiation of Antibiotic Activity of Aztreonam against Metallo-ß-Lactamase-Producing Multidrug-Resistant Pseudomonas aeruginosa by 3-O-Substituted Difluoroquercetin Derivatives.

The combination of aztreonam (ATM) and ceftazidime-avibactam (CAZ-AVI; CZA) has shown therapeutic potential against serine-ß-lactamase (SBL)- and metallo-ß-lactamase (MBL)-producing Enterobacterales. However, the ability of CZA to restore the antibiotic activity of ATM is severely limited in MBL-producing multidrug-resistant (MDR) Pseudomonas aeruginosa strains because of the myriad of intrinsic and acquired resistance mechanisms associated with this pathogen. We reasoned that the simultaneous inhibition of multiple targets associated with multidrug resistance mechanisms may potentiate the antibiotic activity of ATM against MBL-producing P. aeruginosa. During a search for the multitarget inhibitors through a molecular docking study, we discovered that di-F-Q, the previously reported efflux pump inhibitor of MDR P. aeruginosa, binds to the active sites of the efflux pump (MexB), as well as various ß-lactamases, and these sites are open to the 3-O-position of di-F-Q. The 3-O-substituted di-F-Q derivatives were thus synthesized and showed hereto unknown multitarget MDR inhibitory activity against various ATM-hydrolyzing ß-lactamases (AmpC, KPC, and New Delhi metallo-ß-lactamase (NDM)) and the efflux pump of P. aeruginosa, presumably by forming additional hydrophobic contacts with the targets. The multitarget MDR inhibitor 27 effectively potentiated the antimicrobial activity of ATM and reduced the MIC of ATM more than four-fold in 19 out of 21 MBL-producing P. aeruginosa clinical strains, including the NDM-producing strains which were highly resistant to various combinations of ATM with ß-lactamase inhibitors and/or efflux pump inhibitors. Our findings suggest that the simultaneous inhibition of multiple MDR targets might provide new avenues for the discovery of safe and efficient MDR reversal agents which can be used in combination with ATM against MBL-producing MDR P. aeruginosa.

Dynamics of surface-plasmon lasing in planar metal gratings on semiconductor.

We investigate the dynamics of surface plasmon (SP) lasing in Au gratings fabricated on InGaAs with a period of around 400 nm, which locates the SP resonance near the semiconductor energy gap and facilitates efficient energy transfer. By optically pumping the InGaAs to reach the population inversion required for the amplification and the lasing, we observe SP lasing at specific wavelengths that satisfy the SPR condition depending on the grating period. The carrier dynamics in semiconductor and the photon density in the SP cavity was investigated from the time-resolved pump-probe measurement and the time resolved photoluminescence spectroscopy, respectively. Our results reveal that the photon dynamics is strongly correlated with the carrier dynamics and the lasing build-up is accelerated as the initial gain proportional to the pumping power increases, and this trend is satisfactorily explained using the rate equation model.

Sterilization effects of UV laser irradiation on Bacillus atrophaeus spore viability, structure, and proteins.

Bacillus spores are highly resistant to toxic chemicals and extreme environments. Because some Bacillus species threaten public health, spore inactivation techniques have been intensively investigated. We exposed Bacillus atrophaeus spores to a 266 nm Nd:YVO4 laser at a laser power of 1 W and various numbers of scans. As a result, the UV laser reduced the viability of Bacillus atrophaeus spores. Although the outer coat of spores remained intact after UV laser irradiation of 720 scans, damage inside the spores was observed. Spore proteins were identified by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry during the course of UV laser irradiation. Photochemical and photothermal processes are believed to be involved in the UV laser sterilization of Bacillus spores. Our findings suggest that a UV laser is capable of sterilizing Bacillus atrophaeus spores.

Anisotropic Generation and Detection of Coherent Ag Phonons in Black Phosphorus.

Black phosphorus (BP) has attracted great attention due to its layer-tuned direct bandgap, in-plane anisotropic properties, and novel optoelectronic applications. In this work, the anisotropic characteristics of BP crystal in terms of the Raman tensor and birefringence are studied by investigating polarization dependence in both the generation and detection of Ag mode coherent phonons. While the generated coherent phonons exhibit the typical linear dichroism of BP crystal, the detection process is found here to be influenced by anisotropic multiple thin film interference, showing wavelength and sample thickness sensitive behaviors. We additionally find that the Ag1 and Ag2 optical phonons decay into lower frequency acoustic phonons through the temperature-dependent anharmonic process.

Enhanced optical absorption in conformally grown MoS2 layers on SiO2/Si substrates with SiO2 nanopillars with a height of 50 nm.

The integration of transition metal dichalcogenide (TMDC) layers on nanostructures has attracted growing attention as a means to improve the physical properties of the ultrathin TMDC materials. In this work, the influence of SiO2 nanopillars (NPs) with a height of 50 nm on the optical characteristics of MoS2 layers is investigated. Using a metal organic chemical vapor deposition technique, a few layers of MoS2 were conformally grown on the NP-patterned SiO2/Si substrates without notable strain. The photoluminescence and Raman intensities of the MoS2 layers on the SiO2 NPs were larger than those observed from a flat SiO2 surface. For 100 nm-SiO2/Si wafers, the 50 nm-NP patterning enabled improved absorption in the MoS2 layers over the whole visible wavelength range. Optical simulations showed that a strong electric-field could be formed at the NP surface, which led to the enhanced absorption in the MoS2 layers. These results suggest a versatile strategy to realize high-efficiency TMDC-based optoelectronic devices.

Valley depolarization in monolayer transition-metal dichalcogenides with zone-corner acoustic phonons.

Although single-layer transition-metal dichalcogenides with novel valley functionalities are a promising candidate to realize valleytronic devices, the essential understanding of valley depolarization mechanisms is still incomplete. Based on pump-probe experiments performed for MoSe2 and WSe2 monolayers and corroborating analysis from density functional calculations, we demonstrate that coherent phonons at the K-point of the Brillouin zone can effectively mediate the valley transfer of electron carriers. In the MoSe2 monolayer case, we identify this mode as the flexural acoustic ZA(K) mode, which has broken inversion symmetry and thus can enable electron spin-flip during valley transfer. On the other hand, in the monolayer WSe2 case where spin-preserving inter-valley relaxations are preferred, coherent LA(K) phonons with even inversion symmetry are efficiently generated. These findings establish that while the specifics of inter-valley relaxations depend on the spin alignments of energy bands, the K-point phonons should be taken into account as an effective valley depolarization pathway in transition metal dichalcogenide monolayers.

Polarization-Dependent Light Emission and Charge Creation in MoS2 Monolayers on Plasmonic Au Nanogratings.

We fabricated plasmonic hybrid nanostructures consisting of MoS2 monolayer flakes and Au nanogratings with a period of 500 nm. The angle-resolved reflectance and photoluminescence spectra of the hybrid nanostructures clearly indicated a coupling between surface plasmon polaritons (SPPs) and incoming photons. The surface photovoltage (SPV) maps could visualize the spatial distribution of net charges while shining light on the sample. Considerable polarization and wavelength dependence of the SPV signals suggested that the SPP mode enhanced the light-matter interaction and resulting exciton generation in the MoS2 monolayer. From the photoluminescence spectra and the morphology of the suspended MoS2 region, it could be noted that light irradiation did not much raise the temperature of the MoS2 monolayers on the nanogratings. Nanoscopic SPV and surface topography measurements could reveal the local optoelectronic and mechanical properties of MoS2 monolayers. This work provided us insights into the proposal of a high-performance MoS2/metal optoelectronic devices, based on the understanding of the SPP-photon and SPP-exciton coupling.

Effective Photoluminescence Imaging of Bubbles in hBN-Encapsulated WSe2 Monolayer.

Interfacial bubbles are unintentionally created during the transfer of atomically thin 2D layers, a required process in the fabrication of van der Waals heterostructures. By encapsulating a WSe2 monolayer in hBN, we study the differing photoluminescence (PL) properties of the structure resulting from bubble formation. Based on the differentiated absorption probabilities at the bubbles compared to the pristine areas, we demonstrate that the visibility of the bubbles in PL mapping is enhanced when the photoexcitation wavelength lies between the n = 1 and n = 2 resonances of the A-exciton. An appropriate choice of detection window, which includes localized exciton emission but excludes free exciton emission, further improves bubble imaging capability. The interfacial position dependence of the bubbles, whether they are located above or below the WSe2 monolayer, gives rise to measurable consequences in the PL shape.

Self-consistent dielectric constant determination for monolayer WSe2.

Frequency-dependent dielectric constant dispersion of monolayer WSe2, ε(ω)=ε1(ω)+i Îµ2(ω), was obtained from simultaneously measured transmittance and reflectance spectra. Optical transitions of the trion as well as A-, B-, and C-excitons are clearly resolved in the  Îµ2 spectrum. A consistent Kramers-Kronig transformation between the ε1 and  Îµ2 spectra support the validity of the applied analysis. It is found that the A- and B-exciton splitting in the case of the double-layer WSe2 can be attributed to the spin-orbit coupling, which is larger than that in the monolayer WSe2. In addition, the temperature-induced evolution of the A-exciton energy and its width are explained by model equations with electron-phonon interactions.

McGrath Video Laryngoscopy Facilitates Routine Nasotracheal Intubation in Patients Undergoing Oral and Maxillofacial Surgery: A Comparison With Macintosh Laryngoscopy.

PURPOSE: The McGrath video laryngoscope (VL) offers excellent laryngoscopic views and increases the success rate of orotracheal intubation in patients with normal and difficult airways. The purpose of this randomized controlled trial was to compare the McGrath VL with the Macintosh laryngoscope to investigate the efficacy of the McGrath VL for routine nasotracheal intubation in patients with an expected normal airway. MATERIALS AND METHODS: To address the research purpose, the efficacy of the McGrath VL for routine nasotracheal intubation was compared with that of the Macintosh laryngoscope. The predictor variable was the laryngoscopic technique (McGrath VL vs Macintosh laryngoscope). The outcome variables were the time to successful intubation, laryngoscopic views before and after optimal external laryngeal manipulation (OELM), use of Magill forceps, ease of intubation, and severity of oropharyngeal bleeding. RESULTS: Data from 35 patients undergoing oral and maxillofacial surgery were assessed. The time to intubation was 10.5 seconds shorter in the McGrath group than in the Macintosh group (34.4 ± 13.7 vs 44.9 ± 15.6 seconds; P = .004). The incidence of grade 1 glottic view before OELM was higher in the McGrath group than in the Macintosh group (83 vs 57%; P = .019). The frequency of Magill forceps use was lower in the McGrath group than in the Macintosh group (6 vs 34%; P = .003). CONCLUSION: McGrath VL facilitates routine nasotracheal intubation in expected normal airways by providing a shorter intubation time and better laryngoscopic views compared with the Macintosh laryngoscope.