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The Sakigake designation system (Sakigake) has been launched to encourage the pioneered development of innovative new medical products for the effective treatment of severe illness in Japan, which allows leveraging the several advantages in prioritized consultation, rapid review, premium drug pricing and extended data-protection period. We retrospectively analysed the Sakigake products including drugs and regenerative medical products to clarify the achievements and the future issues in this system. From April 2015 to August 2020 (the first 5-year trial period of Sakigake), 37 products were designated, and 10 of those were approved in Japan in which 7 new active substances achieved the first-in-world approvals. Oncology, neurology and cardiovascular disease were the major therapeutic areas, and those 3 accounted for 75.7% of all products. Sakigake achieved some first-in-world approvals by the Pharmaceuticals and Medical Devices Agency/the Ministry of Health, Labor and Welfare of innovative new medical products, although in some therapeutic areas, there remains room in stimulating drug development.

Deciphering rich non-covalent interactions that govern many chemical and biological processes is crucial for the design of drugs and controlling molecular assemblies and their chemical transformations. However, real-space characterization of these weak interactions in complex molecular architectures at the single bond level has been a longstanding challenge. Here, we employed bond-resolved scanning probe microscopy combined with an exhaustive structural search algorithm and quantum chemistry calculations to elucidate multiple non-covalent interactions that control the cohesive molecular clustering of well-designed precursor molecules and their chemical reactions. The presence of two flexible bromo-triphenyl moieties in the precursor leads to the assembly of distinct non-planar dimer and trimer clusters by manifold non-covalent interactions, including hydrogen bonding, halogen bonding, C–H⋯π and lone pair⋯π interactions. The dynamic nature of weak interactions allows for transforming dimers into energetically more favourable trimers as molecular density increases. The formation of trimers also facilitates thermally-triggered intermolecular Ullmann coupling reactions, while the disassembly of dimers favours intramolecular cyclization, as evidenced by bond-resolved imaging of metalorganic intermediates and final products. The richness of manifold non-covalent interactions offers unprecedented opportunities for controlling the assembly of complex molecular architectures and steering on-surface synthesis of quantum nanostructures., A real-space characterization of dynamic non-covalent interactions in molecular assemblies and chemical reactions at the atomic bond level.

The Pharmaceuticals and Medical Devices Agency (PMDA) has approved hundreds of new drugs in recent years. We retrospectively analyzed the new drugs approved in Japan from 2008 to 2019, and identify the first-in-world approvals and clarify the current drug lag. The new drug and the drug lag were defined as a drug with a new active substance and a difference between the approval date in Japan and the international birth date, respectively. Among 400 new drugs approved in Japan during the last 12 years, 80 (20.0%) were first approved in Japan, and 320 were outside Japan (the United States: 202, 50.5%; Europe: 82, 20.5%; other regions: 36, 9.0%). Of these, 45 new drugs have not yet been approved outside Japan, and the remaining 355 have been globally approved in Japan and overseas. The number of new drug approvals were the largest in oncology followed by metabolic/endocrine and infectious diseases. The median drug lags (year) among all 400 new drugs and 355 new drugs with global approvals were 4.3 and 4.7 in the first tertile (2008-2011), 1.5 and 2.6 in the second tertile (2012-2015), and reduced to 1.3 and 2.2 in the third tertile (2016-2019), respectively. Substantial drug lag remains in neurology, psychiatry, and therapeutic areas where the number of new drug approvals was relatively small. Collectively, one-fifth of the new drugs approved in Japan are first-in-world approvals. Drug lag has been greatly decreased, although it still exists.

Performing bottom-up synthesis by using molecules adsorbed on a surface is an effective method to yield functional polycyclic aromatic hydrocarbons (PAHs) and nanocarbon materials. The intramolecular cyclodehydrogenation of hydrocarbons is a critical process in this synthesis; however, thus far, its elementary steps have not been elucidated thoroughly. In this study, we utilize the metal tip of a low-temperature noncontact atomic force microscope as a manipulable metal surface to locally activate dehydrogenation for PAH-forming cyclodehydrogenation. This method leads to the dissociation of a H atom of an intermediate to yield the cyclodehydrogenated product in a target-selective and reproducible manner. We demonstrate the metal-tip-catalyzed dehydrogenation for both benzenoid and nonbenzonoid PAHs, suggesting its universal applicability as a catalyst for nanographene synthesis.

Aim To evaluate outcomes as well as prognostic factors of transarterial chemoembolization (TACE) in intermediate-stage hepatocellular carcinoma (HCC) with preserved liver function to determine positioning of TACE. Methods Of 158 treatment-naive patients with intermediate-stage HCC who received initial TACE from February 2007 to January 2016, 113 patients met the following inclusion criteria: no combined therapy within 4 weeks after initial TACE, and Child-Pugh score under 7. Response rate and overall survival were evaluated. The prognostic factors were investigated in univariate and multivariate analyses using Cox proportional hazards models. The deterioration of liver function after repeated TACE was also evaluated. Results The response rate was 92.7% (complete response, 63.3%; partial response, 29.4%). The median survival time was 45.2 months. Survival rates at 1, 2, and 3 years were 90.4%, 77.0%, and 60.8% respectively. Age ≥ 75 years (P = 0.022), serum α-fetoprotein level ≥ 200 ng/mL (P = .010), tumor number ≥ 11 (P = 0.008), and heterogeneous enhancement on dynamic computed tomography (P = 0.024) were poor prognostic factors. The deterioration rate of Child-Pugh score and albumin-bilirubin grade was 18.5% and 12.3%, respectively, after the first TACE, 15.6% and 5.1%, respectively, after the second TACE, and 14.5% and 11.1%, respectively, after the third TACE. Conclusion Superselective TACE can achieve high tumor response rates with prolonged overall survival for patients with intermediate-stage HCC with preserved liver function. Age, serum α-fetoprotein level, tumor number ≥ 11, and heterogeneous enhancement on dynamic computed tomography indicated significantly poor prognosis.

Introduction To assess the efficacy of combined therapy involving bland transarterial embolization using gelatin sponge particles (bland GS-TAE) followed by transarterial chemoembolization using lipiodol mixed with anticancer agents and GS particles (Lip-TACE) to reduce the adverse events and increase the therapeutic effect of Lip-TACE in the treatment of huge (≥10 cm) hepatocellular carcinoma (HCC). Material and methods Twenty-one consecutive patients with huge HCCs (≥10 cm in diameter) were enrolled in this study. First, bland GS-TAE was performed to reduce the tumor volume, and then Lip-TACE was performed to control the remaining tumor at intervals of around three weeks. Tumor response, survival, and adverse events of this combined therapy were assessed. Results The tumor response was assessed three months after combined TACE, with complete response in 38.1% and partial response in 57.1% of cases. Severe adverse events were seen in two patients, acute cholecystitis and tumor rupture. The median survival time was 2.7 years, and the one-, two-, three-, and five-year overall survival rates were 76.2%, 66.7%, 42.9%, and 25.0%, respectively. Conclusion Combined therapy involving bland GS-TAE followed by Lip-TACE can be performed safety and may improve survival in patients with huge HCCs.

Ultrathin films consisting of titanium oxide and gold nanoparticles were prepared using a combination of the surface sol–gel process and liquid/liquid interfacial precipitation. The composite films had a titanium oxide/gold nanoparticle layer/titanium oxide film structure, comprising a gold nanoparticle thin-film layer sandwiched within titanium oxide films of nanometer-order thickness. Upon heating the titanium oxide–gold nanoparticle composite films to 450 °C, they underwent a phase change from the amorphous to the anatase phase, which was confirmed via Raman scattering analysis. It was observed that, even after heating, the plasmonic absorption band due to the presence of gold nanoparticles was maintained in the composite films. The photocatalytic degradation efficiencies of methylene blue dye were evaluated in films under 520 nm light irradiation. The results suggested that the sandwich-like structure of this titanium oxide/gold nanoparticle layer/titanium oxide is promising for the visible-light-induced degradation of methylene blue dye.

A comparative study of polyvinylidene fluoride (PVDF) and polycaprolactone (PCL) incorporated with particles of amorphous calcium phosphate on the induction of apatite formation ability in simulated body fluid (SBF)-biomimetic environment has been investigated. PVDF and PCL films containing amorphous calcium phosphate particles were fabricated using the solvent casting method. These amorphous calcium phosphate particles were highly active in inducing apatite formation. Results showed that both PCL and PVDF successfully resulted in apatite formation in SBF. However, it was found that the amount of amorphous calcium phosphate particles and the induction period of the apatite formation in SBF significantly varied for PVDF and PCL. These types of bioactive polymeric composite materials are attractive candidates as bone restorative materials with flexibility as well as high apatite forming ability.

In this study, we aimed to introduce bioactivity to bioinert zirconia by performing sandblasting process and subsequently depositing apatite nuclei (AN), which are fine particles of calcium phosphate precipitated by raising pH of SBF, on the surface of the zirconia samples. By soaking the AN treated zirconia samples in SBF, hydroxyapatite formation was observed in 1 day and high hydroxyapatite-forming ability was attained.

We prepared dimethyl and diaryl 2,5-dialkoxytere-phthalates from dimethyl 2,5-dihydroxyterephthalate in good-to-high yields via alkylation or a sequence of alkylation, hydrolysis, chlorination, and condensation. The absorption spectra of the dialkoxyterephthalates contain a small band at 332-355 nm, which could be assigned to intramolecular charge-transfer transition from the alkoxy to alkoxycarbonyl groups on the basis of theoretical calculations using density functional theory. The dialkoxyterephthalates exhibited blue fluorescence with moderate-to-excellent quantum yields not only in solution but also in the solid state, such as a poly(methyl methacrylate) (PMMA) film and a powder. The solid-state quantum yields of the diisopropoxy-substituted terephthalates were similar or considerably higher than those of the dimethoxy-substituted counterparts. Copolymerization of 2,5-diisopropoxyterephthaloyl chloride and 1,4-butanediol with or without terephthaloyl chloride gave brilliantly blue fluorescent polymers, whose quantum yields were 0.72 and 0.71 in toluene and 0.46 and 0.40 in the neat film, respectively. Furthermore, white emission was achieved when a fluorescent yellow 2,5-diaminoterephthalate was doped into the thin film of the blue fluorescent polymer at 0.4 wt %.

Inpyrfluxam is a new, broad-spectrum, succinate dehydrogenase inhibitor (SDHI) fungicide discovered by the Sumitomo Chemical Company. This compound shows strong growth suppression of Basidiomycota and Ascomycota fungi and efficiently controls Asian soybean rust (ASR). In Brazil, soybean farmers are struggling to control this disease owing to the development of resistance against major fungicides, including SDHIs. Interestingly, inpyrfluxam is effective in controlling ASR, even in fields with putative SDHI-resistant populations, suggesting this compound as a new solution for soybean farmers. The internal code of inpyrfluxam at Sumitomo Chemical is S-2399. It is being developed globally as INDIFLIN with its first registration and sales anticipated in 2020. In this chapter the discovery of inpyrfluxam and its biological profile are reported.

AIMS To clarify the rationales of delay or difference in the review of new drug applications among regulatory authorities for new drugs, those first approved in the world being in Japan. METHODS Among 80 new drugs first approved in Japan from 2008 to 2019, we identified those subsequently approved in the USA or Europe. Significant delays in approval time (boxplot outliers) and the rationales for the delays were assessed among the Pharmaceuticals and Medical Devices Agency (PMDA), the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). RESULTS Of the 80 Japan-first approvals, 25 and 24 were approved in the USA and Europe, respectively, and their median approval times in Japan, the USA and Europe were 285, 334 and 477 days, respectively. Significant delays were identified for pirfenidone (1806 days, FDA), alogliptin benzoate (1856 days, FDA), insulin degludec (1457 days, FDA) and romosozumab (750 days, PMDA; 994 days, FDA; 748 days, EMA). Due to concerns about cardiovascular risk, alogliptin benzoate and insulin degludec were requested for additional clinical trials by the FDA, and romosozumab required a much longer review period than the standard approval time in all three regions. CONCLUSIONS Among the new drugs significantly delayed in approval time in Japan, the USA or Europe, there were some differences in the requirements, the participating regions and the assessment of clinical trials. The regulatory views on the cardiovascular risk also differed among the three regions. These divergences may be associated with the differences in approval histories.

Zirconia is a well-known bioceramic for dental and orthopedic applications due to its mechanical and aesthetic properties. However, it lacks sufficient bioactivity to bond with the living bone. This study was aimed to induce bioactivity to tetragonal zirconia polycrystal (3Y-TZP) by simple biomimetic aqueous solution treatment. First, hydrofluoric acid (HF) etching was performed to enhance the surface roughness of the 3Y-TZP surface. Then, the samples were treated with two types of aqueous solutions containing calcium and phosphate ions (Ca-P solutions), one solution additionally contained magnesium (Mg) ions and the other without Mg ions. Finally, hydroxyapatite (HAp)-forming ability was evaluated by the conventional simulated body fluid (SBF) test, and the effect of Mg ions on the adhesive strength of the HAp layer to the roughened 3Y-TZP surface was also investigated. The results concluded that there were no noticeable differences in the effect of Mg ions on the HAp-forming ability, and both types of solution treatments resulted in dense HAp formation in 1 day SBF immersion. However, incorporation of Mg ions in one of the Ca-P solutions significantly improved the adhesive strength of the HAp layer to the HF-etched 3Y-TZP substrate compared to the Ca-P solution with no Mg ions.

The adsorption configurations of heptahelicene ([7]H) molecules on Cu(001) are investigated with noncontact atomic force microscopy (ncAFM) and scanning tunneling microscopy (STM). Because of the suppression of thermal diffusion at 5 K, racemic [7]H molecules exist as monomers, dimers, trimers, and tetramers on the surface. The terminal naphthaleno part of the molecule is attached horizontally to the substrate so that the two benzene ring centers are located at the hollow sites, whereas the other terminal is protruded toward a vacuum. A procedure for picking a [7]H molecule up from the surface (vertical manipulation) enables us to functionalize the tip apex to enhance the spatial resolution of ncAFM. The ncAFM images with the helicene tip clarify that whereas the tetramers are homochiral, the dimers and trimers are heterochiral. In contrast, homochiral dimers and trimers are unobservable probably because of the rapid formation of the stable homochiral tetramers. Thus, ncAFM imaging can identify the geomet...

The products of two-zone chemical vapor deposition on Au(111) from a Z-bar-linkage precursor with quaterphenyl-branches were investigated by scanning tunneling microscopy, Raman spectroscopy, and theoretical calculations. Annealing at 400 °C produced linear arrays of intramolecular-dehydrogenated precursors, and temperatures over 450 °C led to intermolecular dehydrogenation and to the formation of graphene clusters. This reaction pathway contrasts remarkably with the previous results reported for a Z-bar-linkage precursor with terphenyl branches, where homochiral polymerization proceeded and allowed the formation of acene-type graphene nanoribbons. The reason might originate from the conformation of the biradical form of the quaterphenyl-branched precursor, produced by debromination on Au(111) during 250 °C annealing. The quaterphenyl-branched precursor might favor a symmetric conformation with both the radicals pointing toward the Au(111) surface, whereas our previous results showed that the terphenyl-branched precursor might favor asymmetric (chiral) conformations, with one radical pointing toward and the other one away from the Au(111) surface. Steric hindrance of the symmetric conformations of the quaterphenyl-branched precursor is presumed to prohibit polymerization due to the strong affinity of the biradical to Au(111). Such symmetric precursor conformations lead to fused debrominated precursors via intramolecular dehydrogenation, and finally result in the conversion to graphene clusters via on-surface intermolecular fusion.

The orientation and electronic structure of multilayered graphene nanoribbons with an armchair-edge (AGNRs) were determined by low-temperature scanning tunneling microscopy in this study. The orientation of AGNRs was found to be an edge-on structure when positioned as a top layer, while previous reports showed a face-on structure for monolayered AGNRs on Au(111). According to density functional theory calculations, AGNRs in a top layer preferentially form as edge-on structures rather than face-on structures due to the balance of CH-π and π-π interactions between AGNRs. Scanning tunneling spectroscopy and density functional theory calculations revealed that the electronic structures of multilayered AGNRs are similar to those in a gas-phase due to the lack of interaction between AGNRs and the Au(111) substrate. The observation of AGNRs in mutilayers might suggest the conformation-assisted mechanism of dehydrogenation when there is no contact with the Au(111) substrate.

The fluorescence intensity from rubrene (Rub) in Rub-silver nanoparticle (AgNP) composite film was larger than that in Rub film. The enhancement is most likely attributable to large electric fields...

Gold nanoparticle/titanium oxide composite materials were prepared at low temperature and were used as electron-transport layers for inverted-type organic thin-film solar cells. The application of ...

Controlling the structural deformation of organic molecules can drive unique reactions that cannot be induced only by thermal, optical or electrochemical procedures. However, in conventional organic synthesis, including mechanochemical procedures, it is difficult to control skeletal rearrangement in polycyclic aromatic hydrocarbons (PAHs). Here, we demonstrate a reaction scheme for the skeletal rearrangement of PAHs on a metal surface using high-resolution noncontact atomic force microscopy. By a combination of organic synthesis and on-surface cyclodehydrogenation, we produce a well-designed PAH—diazuleno[1, 2, 3-cd:1′, 2′, 3′-fg]pyrene—adsorbed flatly onto Cu(001), in which two azuleno moieties are highly strained by their mutual proximity. This local strain drives the rearrangement of one of the azuleno moieties into a fulvaleno moiety, which has never been reported so far. Our proposed thermally driven, strain-induced synthesis on surfaces will pave the way for the production of a new class of nanocarbon materials that conventional synthetic techniques cannot attain., 金属表面で分子を曲げて骨格を変える新・有機合成法を開発 --原子間力顕微鏡を用いて炭素骨格変換の可視化に成功--. 京都大学プレスリリース. 2017-07-24.

Magnetic field effects (MFEs) on photon upconversion based on sensitized triplet-triplet annihilation (TTA-UC) are examined in platinum(ii) octaethylporphyrin/9,10-diphenylanthracene (DPA) systems at different DPA concentrations and laser power densities. Positive MFEs on TTA-UC are observed for the first time and are most likely attributable to aggregation of DPA.

π-conjugated systems substituted by electron donors (D) or acceptors (A) are useful platforms for various kinds of organic optoelectronic materials. The exploration and development of new donors and acceptors can expand the possible molecular designs of D–π–A-type electronic structures. Herein we report 2,5-bis(diarylamino)terephthalic acid dithioesters, in which organosulfanylcarbonyl groups serve as electron acceptors, as new fluorophores exhibiting efficient solid-state emission. The absorption spectra of the thioesters in toluene show two bands, with the smaller band located at the longer wavelength corresponding to the intramolecular charge-transfer transition from the diarylamino to organosulfanylcarbonyl groups. The dithioesters are faintly fluorescent in toluene, but exhibit efficient orange-to-red emission in the powder form; therefore, aggregation-induced emission was observed. Compared with the corresponding terephthalic acid diesters, the fluorescence spectra of the dithioesters in the powder form are significantly redshifted.

We report covalently interchain-linked graphene nanoribbons fabricated on Au(111) by a stepwise growth process via two-zone chemical vapor deposition. Prepolymer arrays were grown by surface-assist...

The surface-assisted bottom-up fabrication of graphene nanoribbons (GNRs), which consists of the radical polymerization of precursors followed by dehydrogenation, has attracted attention because of the method's ability to control the edges and widths of the resulting ribbon. Although these reactions on a metal surface are believed to be catalytic, the mechanism has remained unknown. Here, we demonstrate ‘conformation-controlled surface catalysis’: the two-zone chemical vapour deposition of a ‘Z-bar-linkage’ precursor, which represents two terphenyl units linked in a ‘Z’ shape, results in the efficient formation of acene-type GNRs with a width of 1.45 nm through optimized cascade reactions. These precursors exhibit flexibility that allows them to adopt chiral conformations with height asymmetry on a Au(111) surface, which enables the production of self-assembled homochiral polymers in a chain with a planar conformation, followed by dehydrogenation via a conformation-controlled mechanism. This is conceptually analogous to enzymatic catalysis and will be useful for the fabrication of new nanocarbon materials. Metal surfaces have been believed to be catalytic, but the mechanism of catalysis is unknown. Now, graphene nanoribbons (GNRs) can be grown on Au(111) from a ‘Z-bar-linkage' precursor through a conformation-controlled mechanism. Chemical vapour deposition of precursors adopting a chiral conformation produced homochiral polymers, which are dehydrogenated to form GNRs.

We aimed to analyze clinical features and treatment outcomes of otitis media caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), i.e. otitis media with AAV (OMAAV).This survey was performed between December 2013 and February 2014. The study began with a preliminary survey to 123 otolaryngology institutions in Japan to inquire about their experiences with OMAAV patients during the past 10 years, and was followed by a questionnaire survey to investigate clinical and laboratory findings. OMAAV was defined using the criteria described in the text.Two hundred and thirty-five patients classified as OMAAV were enrolled in this study. They were characterized as follows: (1) disease onset with initial signs/symptoms due to intractable otitis media with effusion or granulation, which did not respond to ordinary treatments such as antibiotics and insertion of tympanic ventilation tubes, followed by progressive hearing loss; (2) predominantly female (73%) and older (median age: 68 years); (3) predominantly myeloperoxidase (MPO)-ANCA-positive (60%), followed by proteinase 3 (PR3)-ANCA-positive (19%) and both ANCAs-negative (16%); (4) frequently observed accompanying facial palsy (36%) and hypertrophic pachymeningitis (28%); and (5) disease often involving lung (35%) and kidney (26%) lesions. Four factors associated with OMAAV were found to be related to an unfavorable clinical course threatening the patient's hearing and/or lives, namely facial palsy, hypertrophic pachymeningitis, both ANCAs-negative phenotype, and disease relapse. The occurrence of hypertrophic pachymeningitis was associated with facial palsy (p 0.05), both ANCAs-negative phenotype (p 0.001), and headache (p 0.001). The administration of corticosteroid together with an immunosuppressant was an independent predicting factor for lack of disease relapse (odds ratio [OR] = 1.90, p = 0.03) and an improvement in hearing loss (OR =2.58, p = 0.0002).Since OMAAV has novel clinical features, the disease may be categorized as a subentity for the classification of AAV.

Amorphous titanium oxide/plasmonic gold nanoparticle composite powders were synthesized by a combination of the sol–gel process and ultraviolet light irradiation using light-emitting diode at room temperature. The resultant composite powders were dried at ~50 °C. These amorphous titanium oxide/gold nanoparticle composite powders were heated to 450 °C to obtain crystalline titanium oxide/gold nanoparticles. The formation and microstructure of the titanium oxide/gold nanoparticle composite powders were confirmed by transmission electron microscopy, scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, thermo gravimetry–differential thermal analysis, and optical absorption measurements. A clear plasmonic absorption band due to typical plasmonic gold nanoparticle was observed in both composite powders.

There is a growing interest in metal-free organic luminophores that exhibit phosphorescence at room temperature. We report herein that 1,4-bis(aroyl)-2,5-dibromobenzenes serve as a new class of such luminophores. The bis(aroyl)benzene derivatives were not emissive either in solution or in a doped polymer thin film. In contrast, crystals of bis(aroyl)benzenes showed photoluminescence under ambient conditions, which was subsequently confirmed as phosphorescence with a luminescence lifetime measurement. The emission color ranged from blue to green, depending on the nature of the aroyl groups, and the luminescent quantum yields were 0.05–0.18 at room temperature and 0.38–0.67 at 77 K. In each crystal, several intermolecular interactions such as C=O···H, Br···Br, C=O···Br, F···F, S···H, and MeO···H were observed, which contributed to the restriction of intramolecular motions, thereby diminishing the nonradiative decay process from the triplet excited states.

Introduction of pentagonal units into carbon-based materials is of considerable interest to perturb the geometric and electronic properties of the original structures composed of only hexagonal rings. We succeeded in the synthesis of a dibenzopentalene-linking polymer through C–C bonds between the pentagonal carbon atoms from 5,10-dibromodibenzopentalene under the two-zone chemical vapor deposition (2Z-CVD) and wet conditions. The resulting polymer was characterized by Raman spectroscopy. The present finding would spotlight the polymerization of a compound containing pentagonal moieties to introduce pentagonal units into carbon materials.

Wide graphene nanoribbons (GNRs) were fabricated via two-zone chemical vapor deposition using 4,4′′-dibromo-p-terphenyl as the precursor. Densely packed arrays of poly(p-phenylene) produced on Au(111) using this method could be converted into wide GNRs via interchain fusion by thermal annealing. The field-effect transistor prepared from these GNRs exhibited an excellent on/off current ratio of 1.6 ± 0.6 × 103.

The effect of silver nanoplate (AgPL) on the singlet exciton fission (SF) of rubrene (Rub) was verified by examining the magnetic field effects (MFEs) on the SF of Rub through measuring magnetic field dependence of fluorescence intensity of Rub in two thick Rub polymer-composite films in the absence and the presence of AgPL. The fluorescence intensity of Rub in the Rub-AgPL polymer-composite film was larger than that in the Rub polymer-composite film. The enhancement (1.4 times) must be caused by strong electric fields due to localized surface plasmon resonance (LSPR) of the embedded AgPL near the Rub in polymer matrix. The magnitude of the MFEs in the Rub-AgPL polymer-composite film was almost same as those in the Rub polymer-composite film. These results strongly indicate that the efficiency of SF was enhanced by the LSPR due to the embedded AgPL into the polymer matrix in the Rub-AgPL polymer-composite film.

Effects of silver nanoplate (AgPL) and magnetic field on photon upconversion based on sensitized triplet-triplet annihilation (PUC-TTA) were examined in the system of platinum(II) octaethylporphyrin (PtOEP) and 9,10-diphenylanthracene (DPA), when AgPLs were incorporated into polymer thin films containing PtOEP and DPA. In the presence of AgPL, the PUC emission intensity increased as compared with that in the absence of AgPL. The result is most likely attributable to the localized surface plasmon resonance of AgPL. On the other hand, in the absence of AgPL, the PUC emission intensity decreased in the presence of magnetic field, while in the presence of AgPL, the PUC emission intensity increased drastically in the presence of magnetic field. The synergetic effect of AgPL and magnetic field on the PUC emission intensity in PUC-TTA was observed for the first time. © 2019 The Japan Society of Applied Physics.

To develop an implantable port in which a microcatheter can be inserted for a combination therapy of repeated transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for advanced liver cancer. The design of a currently used implantable port was modified. A funnel part was constructed in the port. The septum was punctured by a 20-gauge indwelling needle, and 2.0-Fr non-tapered microcatheter was inserted into the port. In the in vitro studies, the advance of a microcatheter out of the funnel part was evaluated via seven different septum puncture sites. A 5-Fr indwelling catheter connected to the port was placed in a vascular model, and a microcatheter catheterization was evaluated. In an in vivo study, the port–catheter system was implanted in the hepatic artery in a pig. A microcatheter was percutaneously inserted through the port into the hepatic arterial branches, and embolization was performed. In the in vitro studies, the microcatheter was smoothly advanced out of the port and catheterizations into the hepatic arteries were successful via all septum puncture sites. In the in vivo study, repeated selective embolization through the port was successfully conducted on 7, 14 and 21 days after the implantation. The developed implantable port can be used for repeated catheter insertion into the hepatic artery. The combination of repeated TACE and HAIC could be possible using this device.

The synthesis of a molecular wire assembly is a key technology to construct molecular architectures toward single-molecular organic electronic devices. Two new methods to fabricate highly organized and assembled molecular wires are described: 1. one-dimensionally assembled polythiophene molecular wires by electrochemical epitaxial polymerization; 2. multilayered graphene nanoribbon assemblies by two-z one chemical vapor deposition.

Inverted-type bulk-heterojunction organic thin-film solar cells with incorporated gold nanoparticles were fabricated and evaluated. Gold nanoparticles were incorporated into the hole-transport layer, and subsequently positioned behind the photoactive layer, away from the light-facing side of the solar cell. Incorporation of gold nanoparticles was confirmed by scanning electro microscopy, atomic force microscopy, and transmission absorption spectra. The incorporation of the gold nanoparticles improved the performance of the photovoltaic device, even gold nanoparticles were aggregated in the hole-transport layer.

Radical-polymerized chemical vapor deposition, a new bottom-up method, was developed to produce graphene nanoribbons (GNRs) efficiently, despite the use of extremely low vacuum. Using this technique, a systematic synthesis of a multilayered high-density array of width-controlled sub-1 nm GNRs on a metal surface, with width-dependent band gap, is made possible. GNR films transferred onto insulating substrates behave as an excellent photoconductor.

Single-incision laparoscopic surgery has recently received more attention. We developed a novel simple technique of gasless transumbilical single-incisional laparoscopic-assisted appendectomy (TUSILAA) and retrospectively analyzed our initial experience. TUSILAA has been attempted in 50 consecutive patients with acute appendicitis. The vertical incision through the umbilicus was used for laparoscopic access and the abdominal wall was lifted by a Kent retractor set system. Our technique was successful in 45 out of 50 (90 %) patients. The median operating time was 59 min (range 35–140). The median length of postoperative hospital stay was 4 days (range 2–12). None of the cases were converted to open appendectomy. There were no perioperative surgical complications. Our novel technique, gasless TUSILAA, is safe and feasible with acceptable operative time and excellent cosmetic result. Furthermore, this procedure has the advantage of cost-effectiveness since any disposable instruments including trocars, staplers, or expensive devices are not required. Therefore, this could be used as the first-choice surgical procedure for selected patients with uncomplicated acute appendicitis.

Purpose As stereotactic radiotherapy (SRT) becomes widespread, precise information including number, location, and margin of lesions is required when magnetic resonance (MR) imaging of brain metastasis is performed. We compare methods using 2 separate injections and a single injection for the administration of a double dose of contrast medium for contrastenhanced MR imaging. Materials and methods We divided 40 patients with brain metastasis into 2 groups of 20 patients. Group A received 2 separate injections (0.2 + 0.2 mL/kg) of contrast medium (gadoteridol); Group B received a single injection of the same total dose (0.4 mL/kg). Group A underwent spin echo (SE) T1-weighted imaging (T1WI) and magnetization prepared rapid acquisition with gradient echo sequence (MPRAGE) after each injection, and Group B underwent the same MR studies at the same timing as Group A. We evaluated the number, signal-to-noise ratio (SNR), diameter, margin delineation, and volume of lesions and compared them between early and delayed studies by the 2 methods. Results The number of detected lesions was largest in delayed studies of MPRAGE in both groups. The SNR of the lesions was statistically lower in early studies of Group A than other studies. Delayed studies of Group B showed statistically better margin delineation than other studies on both SE-T1WI and MPRAGE studies. Diameter and enhanced volume were statistically significantly larger on delayed phase than early phase in both groups. Conclusion Use of a single injection of double-dose contrast medium and longer delay time may improve margin delineation of lesions for the study of brain metastasis. Enhanced volume was larger on delayed phase, and it may influence selection of therapeutic strategy.

The purpose of this pilot study was to assess the effectiveness of repeated bland-TAE using small-size microspheres for liver metastases. To date, there have been no publications as to whether bland-TAE could be effective for nonhypervascular liver tumors.Bland-TAE with 100-μm, calibrated microspheres was performed in two chemoresistant patients: one with colorectal metastases and the other with gastric metastases. Both patients had multiple tumors in the entire liver. An implantable port-catheter system was placed in the hepatic artery to conduct repeated embolizations, thereby achieving enough efficacies. Microspheres were injected via the port until the disappearance of the tumor stains. Angiographies via the port were conducted 1, 3, 7, and 14 days after bland-TAE to evaluate the patency of the hepatic artery.The hepatic artery started to recanalize 1 day after TAE and tumor stains appeared again during the 14 days. In both patients, bland-TAE was repeated four times in intervals of 14-21 days. The enhanced CTs showed necrotic changes and the decrease in size of the tumors. The serum CEA level decreased from 2,989 to 70 ng/ml and from 174 to 48 ng/ml, respectively. Bilomas and a liver abscess developed as complications.Repeated bland-TAE using 100-μm microspheres injected via an implantable port-catheter system could be effective for liver metastases, although the caution of biliary injury is needed.