Contagious Aggregation: Transmittable Protein Aggregation in Cellular Communities Initiated by Synthetic Cells.

Aggregation of amyloidogenic proteins causing neurodegenerative diseases is an uncontrollable and contagious process that is often associated with lipid membranes in a highly complex physiological environment. Although several approaches using natural cells and membrane models have been reported, systematic investigations focusing on the association with the membranes are highly challenging, mostly because of the lack of proper molecular tools. Here, we report a new supramolecular approach using a synthetic cell system capable of controlling the initiation of protein aggregation and mimicking various conditions of lipid membranes, thereby enabling systematic investigations of membrane-dependent effects on protein aggregation by visualization. Extending this strategy through concurrent use of synthetic cells and natural cells, we demonstrate the potential of this approach for systematic and in-depth studies on interrogating inter- and intracellularly transmittable protein aggregation. Thus, this new approach offers opportunities for gaining insights into the pathological implications of contagious protein aggregation associated with membranes for neurotoxicity.

Countermeasure for security loophole caused by asymmetric correlations of reference frame independent quantum key distribution with fewer quantum states.

One of the challenging issues in free-space quantum key distribution (QKD) is the requirement of active compensation of the reference frame between the transmitter and receiver. Reference frame independent (RFI) QKD removes active compensation, but it requires more quantum states. A recent proposal can effectively reduce the required quantum states, but this can be achieved assuming the correlations defined in RFI QKD are symmetric. In a real QKD system, such symmetric correlations cannot always be satisfied owing to the device imperfections and optical misalignment. We theoretically analyze the effect of asymmetric correlations. Consequently, we report that the asymmetry causes security loopholes and provide a countermeasure to prevent them. Furthermore, we provide the experimental results of a free-space RFI QKD system to verify the countermeasure for the aforementioned problem. In conclusion, our work provides feasibility of the practical RFI QKD system with fewer quantum states by effectively preventing the security loophole.

Programmable Synthesis of Silver Wheels.

The synthesis of sandwich-shaped multinuclear silver complexes with planar penta- and tetranuclear wheel-shaped silver units and a central anion, [Agn(2-HPB)2(A-)](OTf-)n-1, nAgA, n = 4 or 5 and A- = OH- or F- or Cl-, is reported, along with complete spectroscopic and structural characterization. An NMR mechanistic study reveals that silver complexes were formed in the following order: 2Ag → 3AgH2O → 5AgOH → 4AgOH. The central hydroxides in 4AgOH and 5AgOH exhibit exotic physical properties due to the confined environment inside the complex. The size of these silver wheels can be tuned by changing the central anion or extracting/adding one silver atom. This study provides the facile way to synthesize discrete wheel-shaped multinuclear silver complexes and provides valuable insights into the dynamics of the self-assembly process.

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis.

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.

Hierarchical Self-Assembly of Poly-Pseudorotaxanes into Artificial Microtubules.

Hierarchical self-assembly of building blocks over multiple length scales is ubiquitous in living organisms. Microtubules are one of the principal cellular components formed by hierarchical self-assembly of nanometer-sized tubulin heterodimers into protofilaments, which then associate to form micron-length-scale, multi-stranded tubes. This peculiar biological process is now mimicked with a fully synthetic molecule, which forms a 1:1 host-guest complex with cucurbit[7]uril as a globular building block, and then polymerizes into linear poly-pseudorotaxanes that associate laterally with each other in a self-shape-complementary manner to form a tubular structure with a length over tens of micrometers. Molecular dynamic simulations suggest that the tubular assembly consists of eight poly-pseudorotaxanes that wind together to form a 4.5 nm wide multi-stranded tubule.

Superacid-Mediated Functionalization of Hydroxylated Cucurbit[n]urils.

Herein we report a facile transformation of hydroxylated cucurbit[n]uril (CB[n], n = 6 and 7) to other functionality-conjugated CB[n]s by nucleophilic substitution of the hydroxyl group with a wide range of nitriles and alcohols. The reaction proceeds efficiently via generation of a superelectrophilic carbocation on the CB framework from hydroxylated CB[n]s under superacidic conditions. One of the resulting CB[n] derivatives with reactive functionality, monocarboxylated CB[7], is efficiently conjugated to an enzyme (horseradish peroxidase, HRP) by amide coupling. This provides a CB[7]-conjugated functional biomaterial (CB[7]-HRP) that selectively detects proteins labeled with a guest, adamantylammonium (AdA), based on bioorthogonal high-affinity host-guest interactions between CB[7] and AdA. We demonstrated the potential of overcoming the limitations in preparing reactive functional CB[n] derivatives, enabling the exploration of novel bioapplications of CB[n]-based host-guest chemistry with new CB[n]-conjugated functional materials.

Flexible Energy Harvester Based on Poly(vinylidene fluoride) Composite Films.

In these days, we are facing emerging energy crisis due to depletion of fossil fuels. Therefore, renewable energy which is based on wind energy, mechanical force energy, microwave energy and vibrations energy have attracted a lot of attentions. Piezoelectric energy harvesting is one of the promising renewable energy sources. As the use portable electronic devices increases, the need for portable renewable energy sources further increases. Especially, piezoelectric materials can be the best selection due to their robust properties. In this research, piezoelectric composites were prepared and investigated for piezoelectric energy harvesting applications. In this study, two types of flexible energy harvesters, 0.36BS-0.64PT-PVDF composite and PVDF film, were prepared and analyzed. Due to its high Curie temperature and low lead content, BS-PT is expected to be a substitute for PZT in the near future. The composite materials based on the PVDF and 0.36BS-0.64PT film showed higher open circuit voltage (0.73 V) than PVDF film (0.49 V). Also, the stored voltage of 0.36BS-0.64PT-PVDF composite film was 330 nJ which is 5.68 times higher than 58 nJ for PVDF films. By introducing the piezoelectric BS-PT ceramics, 0.36BS-0.64PT-PVDF composite film shows the enhanced performance such as open circuit voltage, energy and dielectric constant compared with those of PVDF materials. It seems that 0.36BS-0.64PT-PVDF composite film is more suitable for flexible energy device.

Rational Design and Construction of Hierarchical Superstructures Using Shape-Persistent Organic Cages: Porphyrin Box-Based Metallosupramolecular Assemblies.

We report a new approach to building hierarchical superstructures using a shape-persistent porous organic cage, which acts as a premade secondary building unit, and coordination chemistry. To illustrate the principle, a zinc-metalated porphyrin box (Zn-PB), a corner-truncated cubic porous cage, was connected by suitable dipyridyl terminated bridging ligands to construct PB-based hierarchical superstructures (PSSs). The PSSs were stabilized not only by the coordination bonds between Zn ions and bipyridyl-terminated ligands but also by π-π interactions between the corners of the Zn-PB units. By varying the length of the linker, we identified an optimum range of the linker length for construction of PSSs. The PSSs have large void volumes and an extrinsic surface area compared to the parent PBs, which can be exploited for the selective encapsulation and interior functionalization of the PSSs for various applications, including catalysis. We observed that singlet oxygen induced synthesis of the natural product, juglone, is more efficiently catalyzed by PSS-1 than its constituent component Zn-PB.

Cost-effective 400-Gbps micro-intradyne coherent receiver using optical butt-coupling and FPCB wirings.

We present a cost-effective and bandwidth-enhanced 64-Gbaud micro-intradyne coherent receiver based on hybrid integration of InP waveguide-photodetector (WG-PD) and silica planar lightwave circuit (PLC). InP waveguide-photodetector (WG-PD) arrays are simply chip-to-chip bonded and optically butt-coupled to a silica-based dual-polarization optical hybrid chip. Multiple flexible printed circuit boards are adapted for electrical RF and DC wirings, which provide low-cost integration and good RF performance of the receiver. A 3-dB bandwidth of the fabricated coherent receiver is extended to ~36 GHz by optimization of bondwire inductance between the WG-PD array and the transimpedance amplifier (TIA), even when commercial TIAs with a typical bandwidth of ~29 GHz are used. Through optimization of the silica hybrid integrated coherent receiver, 64-Gbaud DP-16QAM signal transmission over 1050-km standard single-mode fiber is successfully demonstrated below a bit error rate of 2 × 10-3. This is the threshold for a soft decision-based forward error correction, at the optical signal to noise ratio of 23.8 dB.

High-speed waveguide photodetector for 64 Gbaud coherent receiver.

A high-speed waveguide photodetector has been successfully fabricated for an integrated coherent receiver. Dual laterally tapered structures are introduced for a spot-size converter. We optimize the responsivity and the polarization-dependent loss of the spot-size converter-integrated waveguide photodetector through the beam propagation method simulation. The waveguide photodetector is designed with electrical as well as optical optimizations. The photodetector provides sufficient alignment tolerance, high responsivity of 0.73 A/W, and low polarization-dependent loss of 0.27 dB, which is in good agreement with the simulation results. By increasing the thickness of the matching layer and the n-doped upper taper, the electrical properties of the photodetector are enhanced. The photodetector has a 3 dB bandwidth of 45 GHz, providing high-speed operation. Through the electrical and optical optimizations, we successfully obtain the high-speed waveguide photodetector for a 64 Gbaud integrated coherent receiver.

Self-aligned deterministic coupling of single quantum emitter to nanofocused plasmonic modes.

The quantum plasmonics field has emerged and been growing increasingly, including study of single emitter-light coupling using plasmonic system and scalable quantum plasmonic circuit. This offers opportunity for the quantum control of light with compact device footprint. However, coupling of a single emitter to highly localized plasmonic mode with nanoscale precision remains an important challenge. Today, the spatial overlap between metallic structure and single emitter mostly relies either on chance or on advanced nanopositioning control. Here, we demonstrate deterministic coupling between three-dimensionally nanofocused plasmonic modes and single quantum dots (QDs) without any positioning for single QDs. By depositing a thin silver layer on a site-controlled pyramid QD wafer, three-dimensional plasmonic nanofocusing on each QD at the pyramid apex is geometrically achieved through the silver-coated pyramid facets. Enhancement of the QD spontaneous emission rate as high as 22 ± 16 is measured for all processed QDs emitting over ∼150-meV spectral range. This approach could apply to high fabrication yield on-chip devices for wide application fields, e.g., high-efficiency light-emitting devices and quantum information processing.

Mono-allyloxylated Cucurbit[7]uril Acts as an Unconventional Amphiphile To Form Light-Responsive Vesicles.

Serendipitously, mono-allyloxylated cucurbit[7]uril (AO1 CB[7]) was discovered to act as an unconventional amphiphile which self-assembles into light-responsive vesicles (AO1 CB[7]VC) in water. Although the mono-allyloxy group, directly tethered on the periphery of CB[7], is much shorter (C4) than the hydrophobic tails of conventional amphiphiles, it played an important role in vesicle formation. Light-activated transformation of the allyloxy group by conjugation with glutathione was exploited as a remote tool to disrupt the vesicle. The vesicle showed on-demand release of cargo upon irradiation by a laser, after they were internalized into cancer cells. This result demonstrated the potential of AO1 CB[7]VC as a new type of light-responsive intracellular delivery vehicle for the release of therapeutic cargo, within cells, on demand.

Widespread Anthropogenic Nitrogen in Northwestern Pacific Ocean Sediment.

Sediment samples from the East China and Yellow seas collected adjacent to continental China were found to have lower δ15N values (expressed as δ15N = [15N:14Nsample/15N:14Nair - 1] × 1000‰; the sediment 15N:14N ratio relative to the air nitrogen 15N:14N ratio). In contrast, the Arctic sediments from the Chukchi Sea, the sampling region furthest from China, showed higher δ15N values (2-3‰ higher than those representing the East China and the Yellow sea sediments). Across the sites sampled, the levels of sediment δ15N increased with increasing distance from China, which is broadly consistent with the decreasing influence of anthropogenic nitrogen (NANTH) resulting from fossil fuel combustion and fertilizer use. We concluded that, of several processes, the input of NANTH appears to be emerging as a new driver of change in the sediment δ15N value in marginal seas adjacent to China. The present results indicate that the effect of NANTH has extended beyond the ocean water column into the deep sedimentary environment, presumably via biological assimilation of NANTH followed by deposition. Further, the findings indicate that NANTH is taking over from the conventional paradigm of nitrate flux from nitrate-rich deep water as the primary driver of biological export production in this region of the Pacific Ocean.

Ferrocene and ferrocenium inclusion compounds with cucurbiturils: a study of metal atom dynamics probed by Mössbauer spectroscopy.

Temperature-dependent 57Fe Mössbauer effect (ME) spectroscopic studies were carried out on ferrocene (Fc), 1,1'-dimethylferrocene (1,1'(CH3)2Fc) and ferrocenium hexafluorophosphate (FcPF6) guest species in cucurbit[n]uril (n = 7, 8) inclusion complexes. The solid inclusion complexes were isolated by freeze-drying of dilute aqueous solutions and/or microwave-assisted precipitation from concentrated mixtures. The presence of genuine 1 : 1 (host : guest) inclusion complexes in the isolated solids was supported by liquid-state 1H and solid-state 13C{1H} MAS NMR, elemental and thermogravimetric analyses, powder X-ray diffraction, FTIR spectroscopy, and diffuse reflectance UV-Vis spectroscopy. The ME spectra of the complexes CB7·Fc and CB7·1,1'(CH3)2Fc consist of well-resolved doublets with hyperfine parameters (isomer shift and quadrupole splitting at 90 K) and temperature-dependent recoil-free fraction data that are very similar to those for the neat parent compounds, Fc and 1,1'(CH3)2Fc, suggesting that the organometallic guest molecules do not interact significantly with the host environment over the experimental temperature range. The ME spectra for CB7·FcPF6 and CB8·FcPF6 consist of a major broad line resonance attributed to a paramagnetic FeIII site. From the temperature-dependence of the recoil-free fraction it is evident that the charged guest species in these systems interact with the host environment significantly more strongly than was observed in the case of the neutral guest species, Fc and 1,1'(CH3)2Fc. Moreover, the ME data indicate that the vibrational amplitude of the ferrocenium guest molecule is significantly larger in the CB8 host molecule than in the CB7 homologue, as expected on the basis of the different cavity sizes.

Manifesting Subtle Differences of Neutral Hydrophilic Guest Isomers in a Molecular Container by Phase Transfer.

Achieving strong host-guest interactions between synthetic hosts and hydrophilic guests in solution is challenging because solvation effects overwhelm other effects. To resolve this issue, we transferred complexes of cucurbit[7]uril (CB[7]) and monosaccharides to the gas phase and report here their intrinsic host-guest chemistry in the absence of solvation effects. It was observed that effective host-guest interactions in the gas phase mediated by ammonium cations allow the differentiation of the monosaccharide isomers in complex with CB[7] upon vibrational excitation. The potential of the unique observation was extended to a quantitative supramolecular analytical method for the monosaccharide guests. The combination of host-guest chemistry and phase transfer presented in this study is an effective approach to overcome current limitations in supramolecular chemistry.

Covalent Self-Assembly and One-Step Photocrosslinking of Tyrosine-Rich Oligopeptides to Form Diverse Nanostructures.

We present covalently self-assembled peptide hollow nanocapsule and peptide lamella. These biomimetic dityrosine peptide nanostructures are synthesized by one-step photopolymerization of a tyrosine-rich short peptide without the aid of a template. This simple approach offers direct synthesis of fluorescent peptide nanocages and free-standing thin films. The simple crosslinked peptide lamella films provide robust mechanical properties with an elastic modulus of approximately 30 GPa and a hardness of 740 MPa. These nanostructures also allow for the design of peptidosomes. The approach taken here represents a rare example of covalent self-assembly of short peptides into nano-objects, which may be useful as microcompartments and separation membranes.

High Affinity Host-Guest FRET Pair for Single-Vesicle Content-Mixing Assay: Observation of Flickering Fusion Events.

Fluorescence-based single-vesicle fusion assays provide a powerful method for studying mechanisms underlying complex biological processes of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)-mediated vesicle fusion and neurotransmitter release. A crucial element of these assays is the ability of the fluorescent probe(s) to reliably detect key intermediate events of fusion pore opening and content release/mixing. Here, we report a new, reliable, and efficient single-vesicle content-mixing assay using a high affinity, fluorophore tagged host-guest pair, cucurbit[7]uril-Cy3 and adamantane-Cy5 as a fluorescence resonance energy transfer (FRET) pair. The power of these probes is demonstrated by the first successful observation of flickering dynamics of the fusion pore by in vitro assay using neuronal SNARE-reconstituted vesicles.

Reversible morphological transformation between polymer nanocapsules and thin films through dynamic covalent self-assembly.

A facile method has been developed for synthesizing polymer nanocapsules and thin films using multiple in-plane stitching of monomers by the formation of reversible disulfide linkages. Owing to the reversibility of the disulfide linkages, the nanostructured materials readily transform their structures in response to environmental changes at room temperature. For example, in reducing environments, the polymer nanocapsules release loaded cargo molecules. Moreover, reversible morphological transformations between these structures can be achieved by simple solvent exchanges. This work is a novel approach for the formation of robust nano/microstructured materials that dynamically respond to environmental stimuli.

Porphyrin Boxes: Rationally Designed Porous Organic Cages.

The porphyrin boxes (PB-1 and PB-2), which are rationally designed porous organic cages with a large cavity using well-defined and rigid 3-connected triangular and 4-connected square shaped building units are reported. PB-1 has a cavity as large as 1.95 nm in diameter and shows high chemical stability in a broad pH range (4.8 to 13) in aqueous media. The crystalline nature as well as cavity structure of the shape-persistent organic cage crystals were intact even after complete removal of guest molecules, leading to one of the highest surface areas (1370 m(2) g(-1)) among the known porous organic molecular solids. The size of the cavities and windows of the porous organic cages can be modulated using different sized building units while maintaining the topology of the cages, as illustrated with PB-2. Interestingly, PB-2 crystals showed unusual N2 sorption isotherms as well as high selectivity for CO2 over N2 and CH4 (201 and 47.9, respectively at 273 K at 1 bar).

Enhanced protection of pathogenic Escherichia coli ingested by a soil nematode Caenorhabditis elegans against sanitizer treatments.

We employed Caenorhabditis elegans as a model to study the effectiveness of sanitizers in killing pathogenic Escherichia coli strains ingested by free-living nematodes. Adult worms that had fed on six pathogenic E. coli strains (highly persistent in the nematode intestine) were treated with three chemical solutions. In planktonic cells, none of the H2O2 and acetic acid treatments influenced the survival of the pathogenic E. coli strains, whereas sodium hypochlorite critically decreased the viability of the strains. Importantly, the survival of the E. coli strains was dramatically increased by persistence in the C. elegans gut under 0.1% sodium hypochlorite, and several strains could survive at a concentration of 0.5%. In addition, all pathogenic E. coli strains in the C. elegans gut survived on the lettuce for 5 days even though they were washed with 0.1% sodium hypochlorite. Taken together, our results indicate that pathogenic E. coli ingested by C. elegans may be protected against washing treatment with commercial sanitizers on raw food materials.