Molecular Editing Enhances Oxidation Resistance of Menaquinone-Targeting Antibiotics Lysocin E and WAP-8294A2.

Lysocin E (1 a) and WAP-8294A2 (2 a) are peptidic natural products with 37- and 40-membered macrocycles, respectively. Compounds 1 a and 2 a have potent antibacterial activities against Gram-positive bacteria and share a unique mode of action. The electron-rich indole ring of d-Trp-10 of 1 a and 2 a interacts with the electron-deficient benzoquinone ring of menaquinone, which is a co-enzyme in the bacterial respiratory chain. Formation of the electron-donor-acceptor complex causes membrane disruption, leading to cell death. Despite the promising activities of 1 a and 2 a, the susceptibility of Trp-10 to oxidative degradation potentially deters the development of these compounds as antibacterial drugs. To address this issue, we replaced the indole ring with more oxidation-resistant aromatics having a similar shape and electron-rich character. Specifically, analogues with benzofuran (1 b/2 b), benzothiophene (1 c/2 c), and 1-naphthalene (1 d/2 d) rings were designed, and chemically prepared by full solid-phase total syntheses. Antibacterial assays of the six analogues revealed similar activities of 1 d/2 d and markedly reduced activities of 1 b/2 b and 1 c/2 c compared with 1 a/2 a. Equipotent 1 d and 2 d both showed high resistance to oxidation by peroxyl radicals. Hence, the present study demonstrates a new molecular editing strategy for conferring oxidation stability on natural products with pharmacologically useful functions.

Construction of Five Tryptophan Isomers and Application of the Isomers to Solid-Phase Total Syntheses of Lysocin E Derivatives.

Tryptophan (Trp) plays a unique role in peptides and proteins as its indole ring possesses an electron-rich character and an N1-H hydrogen-bond donor. Because of its non-rotationally symmetric structure, synthetic alterations of the orientation of the indole ring would modulate the intrinsic structures and functions of peptides and proteins. Here we developed synthetic routes to the five Trp isomers in which the C3-substitution of the indole ring was changed to the C2/4/5/6/7-substitutions, and applied the five monomers to Fmoc-based solid-phase peptide synthesis. Specifically, the five monomers were prepared via Negishi cross-coupling reactions of C2/4/5/6/7-iodoindoles. To demonstrate the applicability of the monomers to the solid-phase synthesis, the five Trp isomers of macrocyclic antibiotic lysocin E were selected as target molecules and synthesized through peptide elongation, on-resin macrocyclization, and global deprotection. The Trp isomers displayed markedly weaker antibacterial activity than the parent natural product, revealing the biological importance of the precise three-dimensional shape of the original Trp residue of lysocin E. The present methods for the preparation and application of these five Trp isomers provide a new strategy for analyzing and modifying the specific functions of numerous Trp-containing peptides and proteins beyond this study.

Ultrafast Frequency-Shift Dynamics at Temporal Boundary Induced by Structural-Dispersion Switching of Waveguides.

We experimentally demonstrate the observation of a frequency-shift dynamics at a temporal boundary in the terahertz (THz) region relying on a scheme that controls the structural dispersion of a metal-semiconductor waveguide. Ultrafast structural-dispersion switching is achieved within a subpicosecond timescale by illuminating a waveguide surface with an optical pump pulse during the propagation of a THz pulse in the waveguide. Owing to the relatively high conversion efficiency, up to 23%, under the condition that the frequency shift is sufficiently larger than the bandwidth of the incident pulse, the rapid variation of the THz frequency around the temporal boundary is directly observed in the time domain.

[Gastric bezoars caused by enteral nutrient gel via gastric fistula in a patient with esophageal cancer].

A 62-year-old man presented to our hospital with difficulty in swallowing. Physical examination and subsequent diagnostic tests identified hypopharyngeal and esophageal carcinoma with tracheal invasion. The patient underwent gastric fistula placement, radiotherapy, and chemotherapy. Palliative care was initiated after recurrence. The patient was later hospitalized for neck pain, and during a routine exchange of the gastric fistula, two large bezoars were found. The enteral nutrient gel was discontinued, cola was administered, and the bezoars gradually reduced. He continued to receive home care, and later when he was hospitalized for mediastinal abscess, no bezoars were identified. This case highlights the possibility of bezoar formation as a rare complication of enteral nutrition gel administration.

Topological Boundary Modes from Translational Deformations.

Localized states universally appear when a periodic potential is perturbed by defects or terminated at its surface. In this Letter, we theoretically and experimentally demonstrate a mechanism that generates localized states through continuous translational deformations of periodic potentials. We provide a rigorous proof of the emergence of the localized states under the deformations. The mechanism is experimentally verified in microwave photonic crystals. We also demonstrate topological phase windings of reflected waves for translated photonic crystals.

Freestanding transparent terahertz half-wave plate using subwavelength cut-wire pairs.

We designed a cut-wire-pair metasurface that works as a transparent terahertz half-wave plate, by matching the electric and magnetic resonances of the structure. Due to the impedance matching nature of the resonances, a large transmission phase shift between the orthogonal polarizations was achieved, while permitting a high transmission. The electric and magnetic responses of the proposed structure were confirmed by evaluating the electric admittance and magnetic impedance. The structure was fabricated on a flexible film and its helicity-conversion function in the terahertz frequency range was experimentally demonstrated. The thickness of the device is less than 1/10 of the working vacuum wavelength, and a high amplitude helicity conversion rate over 80 % was achieved. Finally, using simulations, we demonstrate the feasibility of the gradually rotating cut-wire-pair array in terahertz wave-front control.

Dynamically Babinet-invertible metasurface: a capacitive-inductive reconfigurable filter for terahertz waves using vanadium-dioxide metal-insulator transition.

This paper proposes a reconfigurable planar metamaterial that can be switched between capacitive and inductive responses using local changes in the electrical conductivity of its constituent material. The proposed device is based on Babinet's principle and exploits the singular electromagnetic responses of metallic checkerboard structures, which are dependent on the local electrical conductivity. Utilizing the heating-induced metal-insulator transition of vanadium dioxide (VO2), the proposed meta-material is designed to compensate for the effect of the substrate and is experimentally characterized in the terahertz regime. This reconfigurable metamaterial can be utilized as a switchable filter and as a switchable phase shifter for terahertz waves.

Broadband and energy-concentrating terahertz coherent perfect absorber based on a self-complementary metasurface.

We demonstrate that a self-complementary checkerboard-like metasurface works as a broadband coherent perfect absorber (CPA) when symmetrically illuminated by two counter-propagating incident waves. A theoretical analysis based on wave interference and the results of numerical simulations of the proposed metasurface are provided. In addition, we experimentally demonstrate the proposed CPA in the terahertz regime by using a time-domain spectroscopy technique. We observe that the metasurface can work as a CPA below its lowest diffraction frequency. The size of the absorptive areas of the proposed CPA can be much smaller than the incident wavelength. Unlike conventional CPAs, the presented one simultaneously achieves the broadband operation and energy concentration of electromagnetic waves at the deep-subwavelength scale.

Frequency-Independent Response of Self-Complementary Checkerboard Screens.

This research resolves a long-standing problem on the electromagnetic response of self-complementary metallic screens with checkerboardlike geometry. Although Babinet's principle implies that they show a frequency-independent response, this unusual characteristic has not been observed yet due to the singularities of the metallic point contacts in the checkerboard geometry. We overcome this difficulty by replacing the point contacts with resistive sheets. The proposed structure is prepared and characterized by terahertz time-domain spectroscopy. It is experimentally confirmed that the resistive checkerboard structures exhibit a flat transmission spectrum over 0.1-1.1 THz. It is also demonstrated that self-complementarity can eliminate even the frequency-dependent transmission characteristics of resonant metamaterials.

Cardiac Tamponade and Duodenal Hemorrhage Caused by Inappropriate Use of Dabigatran in a Patient With End-Stage Renal Failure: A Case Report.

A 72-year-old man with end-stage renal failure, receiving 220 mg of dabigatran for chronic atrial fibrillation, was admitted with generalized edema and shortness of breath. Cardiac tamponade caused by pericardial hemorrhage due to inappropriate dabigatran use was treated with pericardial drainage and idarucizumab. Although coagulability normalized, consecutive duodenal hemorrhages occurred, requiring arterial embolization for hemostasis. In cases of severely impaired renal function, the usual dose of idarucizumab may not be sufficient to reverse the effects of dabigatran. Therefore, we considered the need for repeated idarucizumab administration to prevent recurrent bleeding.

Direct creation of a photoinduced metallic structure and its optical properties in the terahertz frequency region.

We investigate the surface electromagnetic characteristics of a photoinduced periodical structure using the attenuated total reflection (ATR) technique in the terahertz frequency region. A wire grating structure is generated at the surface of a silicon prism by irradiation with a spatially modulated, ultrafast pulsed laser. A characteristic minimum due to the excitation of surface waves is observed in the ATR spectrum. The depth profile of the photoinduced carrier layer is also studied. We confirm that the photoinduced structure has metallic properties. This fabrication technique will be developed as a simple method to create "active" structures.