Botrytis cinerea detoxifies the sesquiterpenoid phytoalexin rishitin through multiple metabolizing pathways.

Botrytis cinerea is a necrotrophic pathogen that infects across a broad range of plant hosts, including high-impact crop species. Its generalist necrotrophic behavior stems from its ability to detoxify structurally diverse phytoalexins. The current study aims to provide evidence of the ability of B. cinerea to tolerate the sesquiterpenoid phytoalexin rishitin, which is produced by potato and tomato. While the growth of potato pathogens Phytophthora infestans (late blight) and Alternaria solani (early blight) was severely inhibited by rishitin, B. cinerea was tolerant to rishitin. After incubation of rishitin with the mycelia of B. cinerea, it was metabolized to at least six oxidized forms. Structural analysis of these purified rishitin metabolites revealed a variety of oxidative metabolism including hydroxylation at C7 or C12, ketone formation at C5, and dihydroxylation at the 10,11-olefin. Six rishitin metabolites showed reduced toxicity to P. infestans and A. solani, indicating that B. cinerea has at least 5 distinct enzymatic reactions to detoxify rishitin. Four host-specialized phytopathogenic Botrytis species, namely B. elliptica, B. allii, B. squamosa, and B. tulipae also had at least a partial ability to metabolize rishitin as B. cinerea, but their metabolic capacity was significantly weaker than that of B. cinerea. These results suggest that the ability of B. cinerea to rapidly metabolize rishitin through multiple detoxification mechanisms could be critical for its pathogenicity in potato and tomato.

G-protein-coupled estrogen receptor prevents nuclear factor-kappa B promoter activation by Helicobacter pylori cytotoxin-associated gene A in gastric cancer cells.

Helicobacter pylori is a well-known pathogen that causes chronic gastritis, leading to the development of gastric cancer. This bacterium has also been detected in dogs, and symptoms similar to those in humans have been reported. The cytotoxin-associated gene A (CagA) is involved in pathogenesis through aberrant activation of host signal transduction, including the nuclear factor-kappa B (NF-κB) pathway. We have previously shown the anti-inflammatory effect of the G-protein-coupled estrogen receptor (GPER) via inhibiting of NF-κB activation in several cells. Therefore, here, we investigated the effect of GPER on CagA-mediated NF-κB promoter activity and showed that CagA overexpression in gastric cancer cells activated the NF-κB reporter and induced interleukin 8 (il-8) expression, both of which were inhibited by the GPER agonist.

Flexibly designable wettability gradient for passive control of fluid motion via physical surface modification.

Modified solid surfaces exhibit unique wetting behavior, such as hydrophobicity and hydrophilicity. Such behavior can passively control the fluid flow. In this study, we experimentally demonstrated a wettability-designable cell array consisting of unetched and physically etched surfaces by reactive ion etching on a silicon substrate. The etching process induced a significant surface roughness on the silicon surface. Thus, the unetched and etched surfaces have different wettabilities. By adjusting the ratio between the unetched and etched surface areas, we designed one- and two-dimensional wettability gradients for the fluid channel. Consequently, fine-tuned channels passively realized unidirectional and curved fluid motions. The design of a wettability gradient is crucial for practical and portable systems with integrated fluid channels.

Artificial-intelligence-assisted mass fabrication of nanocantilevers from randomly positioned single carbon nanotubes.

Nanoscale cantilevers (nanocantilevers) made from carbon nanotubes (CNTs) provide tremendous benefits in sensing and electromagnetic applications. This nanoscale structure is generally fabricated using chemical vapor deposition and/or dielectrophoresis, which contain manual, time-consuming processes such as the placing of additional electrodes and careful observation of single-grown CNTs. Here, we demonstrate a simple and Artificial Intelligence (AI)-assisted method for the efficient fabrication of a massive CNT-based nanocantilever. We used randomly positioned single CNTs on the substrate. The trained deep neural network recognizes the CNTs, measures their positions, and determines the edge of the CNT on which an electrode should be clamped to form a nanocantilever. Our experiments demonstrate that the recognition and measurement processes are automatically completed in 2 s, whereas comparable manual processing requires 12 h. Notwithstanding the small measurement error by the trained network (within 200 nm for 90% of the recognized CNTs), more than 34 nanocantilevers were successfully fabricated in one process. Such high accuracy contributes to the development of a massive field emitter using the CNT-based nanocantilever, in which the output current is obtained with a low applied voltage. We further showed the benefit of fabricating massive CNT-nanocantilever-based field emitters for neuromorphic computing. The activation function, which is a key function in a neural network, was physically realized using an individual CNT-based field emitter. The introduced neural network with the CNT-based field emitters recognized handwritten images successfully. We believe that our method can accelerate the research and development of CNT-based nanocantilevers for realizing promising future applications.

The garlic-derived organosulfur compound diallyl trisulphide suppresses tissue factor function.

Tissue factor (TF) is a critical initiator of extrinsic coagulation that sometimes causes thromboembolism. Diallyl trisulphide (DATS) is a secondary metabolite of allicin generated in crushed garlic, with various pharmacological effects. This study aimed to clarify the effect of DATS on the extrinsic coagulation elicited by TF and arteriosclerosis. TF activity was measured using a clotting assay in TF-expressing HL60 cells. DATS inhibited TF activity in a dose-dependent manner. TF expression in TNF-α-stimulated human umbilical vein endothelial cells was examined using real-time PCR and western blotting. DATS inhibited TF mRNA and protein expression induced by TNF-α via inhibition of JNK signalling. The effect of DATS on arteriosclerosis was also examined in apolipoprotein E-deficient mice. DATS administration in these mice tended to decrease atherosclerotic lesion size. These results strongly suggest that DATS prevents thromboembolism triggered by atherosclerosis via the inhibition of plaque formation and TF function.

Macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury.

The liver is an exclusive organ with tremendous regenerative capacity. Liver metabolic functions exhibit spatial heterogeneity, reflecting liver zonation. The mechanisms controlling the proliferation of hepatocytes and the accompanying matrix reconstruction during regeneration have been well explored, but the recovery potential of differentiated metabolic functions and zonation after liver injury remains unclear. We employed a mouse model of carbon tetrachloride (CCl4) induced-acute liver injury with clodronate-induced macrophage depletion to clarify the impact of liver injury on liver metabolism and recovery dynamics of metabolic function and liver zonation during regeneration. Depleting macrophages suppressed tissue remodelling and partially delayed cell proliferation during regeneration after liver injury. In addition, recovery of metabolic functions was delayed by suppressing the tissue remodelling caused by the depleted macrophages. The model revealed that drug metabolic function was resilient against the dysfunction caused by liver injury, but glutamine synthesis was not. Metabolomic analysis revealed that liver branched-chain amino acid (BCAA) and carbohydrate metabolism were suppressed by injury. The plasma BCAA concentration reflected recovery of hepatic function during regeneration. Our study reveals one aspect of the regenerative machinery for hepatic metabolism following acute liver injury.

Diallyl Trisulfide Prevents Obesity and Decreases miRNA-335 Expression in Adipose Tissue in a Diet-Induced Obesity Rat Model.

SCOPE: Diallyl trisulfide (DATS), an organosulfur compound generates in crushed garlic, has various beneficial health effects. A growing body of evidence indicates that miRNAs are involved in the pathology of lifestyle diseases including obesity. The anti-obesogenic effect of garlic is previously reported; however, the effects of DATS on obesity, and the relationship between garlic compounds and the involvement of miRNA remains unclear. Here, the anti-obesogenic activity of DATS and the potential role of miRNA in a diet-induced obesity rat model are investigated. METHODS AND RESULTS: Oral administration of DATS suppressed body and white adipose tissue (WAT) weight gain in rats fed a high-fat diet compared with vehicle-administered rats. DATS lowered the plasma and liver triglyceride levels in obese rats, and decreased lipogenic mRNA levels including those of Srebp1c, Fasn, and Scd1 in the liver. DATS also suppressed de novo lipogenesis in the liver. Transcriptomic analyses of miRNA and mRNA in the epididymal WAT of obese rats using microarrays revealed that DATS decreased miRNA-335 expression and normalized the obesity-related mRNA transcriptomic signatures in epididymal WAT. CONCLUSION: The potent anti-obesogenic effects of DATS and its possible mechanism of action was clearly demonstrated in this study.

Optical Trapping-Polarized Raman Microspectroscopy of Single Ethanol Aerosol Microdroplets: Droplet Size Effects on Rotational Relaxation Time and Viscosity.

Optical trapping-polarized Raman microspectroscopy of single ethanol (EtOH) microdroplets with a diameter (d) of 6.1-16.5 µm levitated in an EtOH vapor-saturated air/N2 gas atmosphere has been explored to elucidate the vibrational and rotational motions of EtOH in the droplets at 22.0 °C. The Raman spectral bandwidth of the C-C stretching vibrational mode observed for an aerosol EtOH microdroplet was narrower than that of bulk EtOH, suggesting that the vibrational/rotational motions of EtOH in the aerosol system were restricted compared to those in the bulk system. In practice, polarized Raman microspectroscopy demonstrated that the rotational relaxation time (τrot) of EtOH in an aerosol microdroplet with d = 16. 5 µm was slower (2.33 ps) than that in a bulk EtOH (1.65 ps), while the vibrational relaxation times (τvib) in the aerosol and bulk EtOH systems were almost comparable with one another: 0.86-0.98 ps. Furthermore, although the τvib value of an aerosol EtOH microdroplet was almost unchanged irrespective of d as described above, the τrot value increased from 2.33 to 3.57 ps with a decrease in d from 16.5 to 6.1 µm, which corresponded to the increase in EtOH viscosity (η) from 1.33 to 2.04 cP with the decrease in d. The droplet size dependences of τrot and η in an aerosol EtOH microdroplet were discussed in terms of the gas/droplet interfacial molecular arrangements of EtOH and Laplace pressure experienced by a spherical EtOH microdroplet in the gas phase.

Fish oil suppresses obesity more potently in lean mice than in diet-induced obese mice but ameliorates steatosis in such obese mice.

This study sought to clarify the antiobesity effects of fish oil (FO) in terms of prevention and amelioration. An isocaloric diet composed of lard or FO was given to lean C57BL/6J mice for the study of prevention and high-fat diet-induced obese (DIO) mice for the study of amelioration for 4 weeks. Body weight gain and food efficiency were potently suppressed by FO in lean mice compared to lard diet-fed mice. Uncoupling protein-1 (UCP-1) expression in inguinal white adipose tissue (WAT) was also significantly induced by FO in lean mice. FO also suppressed body weight gain and food efficiency in DIO mice but did not reduce body weight. FO ameliorated liver steatosis in DIO mice by mildly inducing UCP-1 in inguinal WAT. FO suppressed obesity more potently in lean mice than in DIO mice but ameliorated steatosis in the DIO mice.

Laser-Induced Single-Molecule Extraction and Detection in Aqueous Poly(N-isopropylacrylamide)/1-Butanol Solutions.

We report photothermal phase separation of aqueous poly(N-isopropylacrylamide) (PNIPAM)/1-butanol (BuOH) solutions by focused 1064 nm laser irradiation and subsequent single microparticle formation in the solution. The single microparticle [diameter = ∼10 µm and volume = ∼picoliter (pL)] produced by laser irradiation was optically trapped by the incident 1064 nm laser beam, and this enabled us in situ Raman/fluorescence microspectroscopies of the particle. Raman spectroscopy demonstrated that the particle produced by laser irradiation was composed of PNIPAM and BuOH. In the presence of rhodamine B (RhB) in the solution, RhB was distributed from the water phase to the PNIPAM/BuOH microparticle produced by laser irradiation, as confirmed by fluorescence microspectroscopy. Laser-induced distribution/extraction of RhB to a single PNIPAM/BuOH microparticle was shown to be possible at the RhB concentration as low as 10-14 mol/dm3, where the RhB fluorescence intensity from the particle showed a step-by-step increase by every ∼3 min laser irradiation. This is the first demonstration of laser-induced simultaneous extraction and detection of single RhB molecules in solution.

[Pancreatic Cancer Complicated with Idiopathic Thrombocytopenic Purpura and Treated with Chemotherapy-A Case Report].

A 68-year-old woman presenting with anorexia and epigastric pain was diagnosed with metastatic pancreatic cancer and idiopathic thrombocytopenic purpura(ITP). Chemotherapy was initiated with S-1. Subsequently, gemcitabine was administered in combination with prednisolone. Her platelets returned to normal after the treatment with steroids and chemotherapy, but the treatment could not be withdrawn completely. Pancreatic cancer presenting as idiopathic thrombocytopenic purpura has rarely been reported in the literature. Here, we present our experience and discuss a case of pancreatic cancer complicated with ITP.

Optical Trapping-Microspectroscopy of Single Aerosol Microdroplets in Air: Supercooling of Dimethylsulfoxide Microdroplets.

We report temperature (T = +22.5 ∼ -57.0 °C)-controlled optical trapping of single dimethylsulfoxide (DMSO) droplets with the diameter (d) of 7-15 µm in air. Optically levitated DMSO microdroplets containing 0.1 mol/dm3 (=M) potassium iodide (KI) as an additive for reducing the vapor pressure of DMSO in air have been suggested to take supercooled liquid states even below the freezing temperature (fp) of the bulk DMSO liquid (fp = +18.4 °C in the presence of 0.1 M KI) as seen in bright-field microscopic observations of the droplet. Clear evidence for supercooling of an aerosol DMSO microdroplet below fp has been obtained by in situ optical trapping-polarized Raman microspectroscopy of the droplet down to -14.9 °C. Analysis of the polarized Raman spectral data of an aerosol DMSO droplet (d = ∼10 µm) has demonstrated that the droplet at +22.5, +0.2, or -14.9 °C is characterized by the rotational relaxation time (τrot) of a DMSO molecule in the droplet being 1.95, 2.58, or 3.90 ps, respectively. On the basis of the τrot values and the Stokes-Einstein equation (τrot = 8πa3η/kBT where a, η, kB are the radius (1.883 Å) of a DMSO molecule, the viscosity in DMSO, and the Boltzmann constant, respectively), the η values in the DMSO microdroplet in air at +22.5, +0.2, or -14.9 °C have been estimated to be 2.39, 2.94, or 4.20 cP, respectively, while that of bulk DMSO liquid at +20.5 °C is 1.98 cP. We also report the T-dependence (+22.5 > T > -14.9 °C) of the viscosity in a single aerosol DMSO microdroplet (d = ∼10 µm) and the effects of aerosolization in air on the viscosity in DMSO.

Liquid-liquid interface-promoted formation of a porous molecular crystal based on a luminescent platinum(II) complex.

Porous molecular crystals (PMCs) should function as new-generation functional porous materials, but the selective crystallisation of PMCs is still difficult. Herein we demonstrate that the liquid-liquid interface between the MeOH/H2O mixture and alkanes promotes the crystallisation of a Pt(ii)-based PMC, rather than the nonporous form. This new crystallisation method allows control of not only the porosity but also the luminescence of the Pt(ii) complex crystal.

Further enhancement of the near-field on Au nanogap dimers using quasi-dark plasmon modes.

Metallic nanogap dimers are extremely useful for enhancing surface-enhanced Raman scattering and various nonlinear optical effects employing near-field enhancement effects induced by the localized surface plasmon resonance. However, the metallic nanogap dimers exhibit an intense light scattering due to the strong dipole-dipole interaction between two metallic nanostructures and, therefore, are not necessarily a structural design that exhibits the highest near-field enhancement due to the radiation loss. Here, we propose further enhancement of the near-field on metallic nanogap dimers using quasi-dark plasmon modes. By coupling with gold (Au) nanorods having the same plasmon resonant wavelength, but completely different sizes, a quasi-dark plasmon mode, which reduces the radiation loss slightly, is induced, resulting in the elongation of the plasmon dephasing time. As a result, the signal of surface-enhanced Raman scattering of crystal violet molecules adsorbed on the Au nanogap dimer is enhanced up to about three times as compared to that measured using the Au nanogap dimer without the Au nanorods. Scattering spectrum measurements as well as electromagnetic simulations were performed to clarify the mechanism for further enhancement of the near-field. The proposed coupled plasmonic system is expected to be advantageous, especially in enhancing nonlinear optical effects using plasmonic enhancement effects.

High-aspect-ratio mushroom-like silica nanopillars immersed in air: epsilon-near-zero metamaterials mediated by a phonon-polaritonic anisotropy.

Epsilon-near-zero metamaterials offer opportunities for intriguing electromagnetic-wave phenomena. Here we experimentally demonstrate that silica perpendicular nanopillars immersed in air exhibit a uniaxial epsilon-near-zero response mediated by phonon polaritons in the mid-infrared range. Unique mushroom-shaped heads on nanopillars play a crucial role to realize SiO2 metamaterials over a large area in our self-assembled fabrication process with block copolymers, polystyrene-block-poly(dimethylsiloxane) (PS-b-PDMS). SiO2 nanopillars having heights of 80 nm, 200 nm, and 300 nm (aspect ratios up to ∼13) are obtained after calcination at 450 °C and the electromagnetic responses are evaluated using a mid-infrared ellipsometric apparatus. For nanopillars with 200 nm height, the permittivity of the perpendicular component ε ⊥ approaches to near zero (0.2) while the parallel component ε ‖ shows a value of 1.8. The measured uniaxial epsilon-near-zero responses are excellently reproduced by the effective medium theory. Our results, therefore, indicate that SiO2 nanopillars/air uniaxial epsilon-near-zero metamaterials in the mid-infrared range can be amenable to large scale fabrication.

Ferroelectricity and Piezoelectricity in Free-Standing Polycrystalline Films of Plastic Crystals.

Plastic crystals represent a unique compound class that is often encountered in molecules with globular structures. The highly symmetric cubic crystal structure of plastic crystals endows these materials with multiaxial ferroelectricity that allows a three-dimensional realignment of the polarization axes of the crystals, which cannot be achieved using conventional molecular ferroelectric crystals with low crystal symmetry. In this work, we focused our attention on malleability as another characteristic feature of plastic crystals. We have synthesized the new plastic/ferroelectric ionic crystals tetramethylammonium tetrachloroferrate(III) and tetramethylammonium bromotrichloroferrate(III), and discovered that free-standing translucent films can be easily prepared by pressing powdered samples of these compounds. The thus obtained polycrystalline films exhibit ferroelectric polarization switching and a relatively large piezoelectric response at room temperature. The ready availability of functional films demonstrates the practical utility of such plastic/ferroelectric crystals, and considering the vast variety of possible constituent cations and anions, a wide range of applications should be expected for these unique and attractive functional materials.

Effects of pharmacological inhibition of plasminogen binding on liver regeneration in rats.

The fibrinolysis system is thought to play an important role in liver regeneration. We previously found that plasminogen (Plg) is localized to the cell surface of regenerating liver tissue as well as proliferating hepatocytes in vitro. Here, we investigated the significance of Plg binding to the cell surface during liver regeneration. Pre-administration of tranexamic acid (TXA), which is a competitive inhibitor of Plg binding, to hepatectomized rats mildly delayed restoration of liver weight in vivo. Although binding of Plg to the cell membrane decreased following TXA administration, TXA showed little effect on hepatocyte proliferation in rats. We also discovered that Plg treatment did not stimulate proliferation of primary rat hepatocytes in vitro. These results suggest that Plg/plasmin potentiates liver regeneration via a pathway distinct from those through which hepatocyte proliferation is stimulated.

Dynamic Modulation of Radiative Heat Transfer beyond the Blackbody Limit.

Dynamic control of electromagnetic heat transfer without changing mechanical configuration opens possibilities in intelligent thermal management in nanoscale systems. We confirmed by experiment that the radiative heat transfer is dynamically modulated beyond the blackbody limit. The near-field electromagnetic heat exchange mediated by phonon-polariton is controlled by the metal-insulator transition of tungsten-doped vanadium dioxide. The functionalized heat flux is transferred over an area of 1.6 cm2 across a 370 nm gap, which is maintained by the microfabricated spacers and applied pressure. The uniformity of the gap is validated by optical interferometry, and the measured heat transfer is well modeled as the sum of the radiative and the parasitic conductive components. The presented methodology to form a nanometric gap with functional heat flux paves the way to the smart thermal management in various scenes ranging from highly integrated systems to macroscopic apparatus.

Simple and scalable preparation of master mold for nanoimprint lithography.

Nanoimprint lithography (NIL) is one of the most prominent bottom-up techniques for duplicating nanostructures with a high throughput. However, fabrication of starting master mold commonly requires expensive equipment of top-down techniques, or additional steps to transfer the fabricated patterns from bottom-up methods. Here we demonstrate that a SiO2 nanostructure manufactured from a self-assembled block copolymer, polystyrene-b-polydimethylsiloxane (PS-b-PDMS), directly serves as a master mold for NIL without further modification. A hexagonally aligned pattern over the entire substrate is established using a simple technique; solvent annealing and etching. Etching also plays an important role in endowing fluorine on the surface of SiO2, thus promoting smooth demolding upon imprinting. The obtained pattern of the SiO2 nanostructure is transferred to a polymer surface using UV nanoimprint. Identical patterns of the SiO2 nanostructure are elaborately reproduced on Ni and Cu nanodot arrays via electroplating on the polymer transcript, which was verified by morphological observations. The uniformity of the replicated Ni nanodot array is evaluated using spectroscopic ellipsometry. The measured optical response of the Ni nanodot is validated by electromagnetically simulated results, indicating that the pattern transfer is not limited to a small local area. In addition, the durability of the SiO2 mold pattern is corroborated after the imprinting process, thus guaranteeing the reusability of the fabricated nanostructure as a master mold. The proposed approach does not require any high-end lithographic techniques; this may result in significant cost and time reductions in future nanofabrication.

Rapid and reversible photoinduced switching of a rotaxane crystal.

Crystalline phase transitions caused by external stimuli have been used to detect physical changes in the solid-state properties. This study presents the mechanical switching of crystals of ferrocene-containing rotaxane controlled by focused laser light. The expansion and contraction of the crystals can be driven by turning on and off laser light at 445 nm. The irradiation-induced expansion of the crystal involves elongation along the a, b and c axes at 30 °C, whereas heating of the crystal at 105 °C causes the shortening of c axis. The expansions reversibly occur and have the advantage of a rapid relaxation (reverse) process. Single-crystal X-ray crystallography reveals the detailed structural changes of the molecules, corresponding to a change in the size of the crystals on laser irradiation. This molecular crystal behaviour induced by laser irradiation, is demonstrated for the remote control of objects, namely, microparticle transport and microswitching in an electric circuit.