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We present a systematic review of the methods developed for the synthesis of the aromathecin family of compounds (benz[6,7]indolizino[1,2-b]quinolin-11(13H)-ones) and their derivatives. These methods can be broadly classified into four categories based on the construction of pentacyclic structures: Category 1: by constructing a pyridone moiety (D-ring) on the pyrroloquinoline ring (A/B/C-ring), Category 2: by constructing a pyridine moiety (B-ring) on the pyrroloisoquinolone ring (C/D/E-ring), Category 3: by constructing an indolizidinone moiety (C/D-ring) in a tandem reaction, and Category 4: by constructing a pyrrolidine moiety (C-ring) on the isoquinolone ring (D/E-ring). [ABSTRACT FROM AUTHOR]

Camptothecin-like compounds are actively employed as anticancer drugs in clinical treatments. The aromathecin family of compounds, which contains the same indazolidine core structure as the camptothecin family of compounds, is also expected to display promising anticancer activity. Therefore, the development of a suitable and scalable synthetic method of aromathecin synthesis is of great research interest. In this study, we report the development of a new synthetic approach for constructing the pentacyclic scaffold of the aromathecin family by forming the indolizidine moiety after synthesizing the isoquinolone moiety. Thermal cyclization of 2-alkynylbenzaldehyde oxime to the isoquinoline N-oxide, followed by a Reissert–Henze-type reaction, forms the key strategy in this isoquinolone synthesis. Under the optimum reaction conditions for the Reissert–Henze-type reaction step, microwave irradiation-assisted heating of the purified N-oxide in acetic anhydride at 50 °C reduced the formation of the 4-acetoxyisoquinoline byproduct to deliver the desired isoquinolone at a 73% yield after just 3.5 h. The eight-step sequence employed afforded rosettacin (simplest member of the aromathecin family) at a 23.8% overall yield. The synthesis of rosettacin analogs was achieved by applying the developed strategy and may be generally applicable to the production of other fused indolizidine compounds. [ABSTRACT FROM AUTHOR]

Melzer then presents an engaging study of knowledge transfer from the United States and Germany, concluding with a survey history of Japanese aviation after 1945 (epilogue). Vast scholarship, in English and even more so in Japanese, has often emphasized the successive stages of technology transfer within the aircraft industry, underscoring the French, British, and German influences on the shaping of Japanese aviation. This "new perspective", in the author's words (p. 1), provides fresh insights into the scholarship of Japan's aviation history and technology transfer at large. [Extracted from the article]

• Our HEV replication monitoring system uses Gaussia luciferase. • We validated candidates using cells robustly producing HEV. • We screened and evaluated anti-HEV drugs with an FDA-approved drug library. • Interferon λ1-3 inhibited HEV propagation in our new system. Hepatitis E, which is caused by hepatitis E virus (HEV), is generally a self-limiting, acute, and rarely fatal disease. It is sometimes fulminant and lethal, especially during pregnancy. Indeed, it occasionally takes a chronic course in immunocompromised individuals. To cure hepatitis E patients, the broad-spectrum antivirals (ribavirin and pegylated interferon α) are used. However, this treatment is insufficient and unsafe in some patients due to embryoteratogenic effects, leukopenia, and thrombocytopenia. In this study, we constructed an HEV replication reporter system with Gaussia luciferase for comprehensively screening anti-HEV drug candidates, and developed a cell-culture system using cells robustly producing HEV to validate the efficacy of anti-HEV drug candidates. We screened anti-HEV drug candidates from United States Food and Drug Administration-approved drugs using the established HEV replication reporter system, and investigated the selected candidates and type III interferons (interferon λ1-3) using the cell-culture system. In conclusion, we constructed an HEV replicon system for anti-HEV drug screening and a novel cell-culture system to strictly evaluate the replication-inhibitory activities of the obtained anti-HEV candidates. Our findings suggested that interferon λ1-3 might be effective for treating hepatitis E. [ABSTRACT FROM AUTHOR]

We developed a concise protocol for the synthesis of ellipticine quinone from the appropriate 3-iodoindole-2-carbaldehydes in four steps. The key step is the construction of carbazole-1,4-quinone through tandem Ring-Closing Metathesis (RCM) and dehydrogenation under oxygen atmosphere. Therefore, the ellipticine quinone analogs possessing substitution at the 8- and/or 9-positions were synthesized using this method. In total, 14 compounds were evaluated for antiproliferative activity against HCT-116 and HL-60 cell lines; 9-nitroellipticine quinone was found to have superior activity compared to calothrixin B. [ABSTRACT FROM AUTHOR]

The hepatitis E virus (HEV) is increasingly acknowledged as the primary cause of acute hepatitis. While most HEV infections are self-limiting, cases of chronic infection and fulminant hepatitis necessitate the administration of anti-HEV medications. However, there is a lack of specific antiviral drugs designed for HEV, and the currently available drug (ribavirin) has been associated with significant adverse effects. The development of innovative antiviral drugs involves targeting distinct steps within the viral life cycle: the early step (attachment and internalization), middle step (translation and RNA replication), and late step (virus particle formation and virion release). We recently established three HEV reporter systems, each covering one or two of these steps. Using these reporter systems, we identified various potential drug candidates that target different steps of the HEV life cycle. Through rigorous in vitro testing using our robust cell culture system with the genotype 3 HEV strain (JE03-1760F/P10), we confirmed the efficacy of these drugs, when used alone or in combination with existing anti-HEV drugs. This underscores their significance in the quest for an effective anti-HEV treatment. In the present review, we discuss the development of the three reporter systems, their applications in drug screening, and their potential to advance our understanding of the incompletely elucidated HEV life cycle. [ABSTRACT FROM AUTHOR]

Three to eight percent of female carriers of Duchenne muscular dystrophy (DMD) develop dystrophic symptoms ranging from mild muscle weakness to a rapidly progressive DMD-like muscular dystrophy due to skewed inactivation of X chromosomes during early development. Here, we generated human induced pluripotent stem cells (hiPSCs) from a manifesting female carrier using retroviral or Sendai viral (SeV) vectors and determined their X-inactivation status. Although manifesting carrier-derived iPS cells showed normal expression of human embryonic stem cell markers and formed well-differentiated teratomas in vivo, many hiPS clones showed bi-allelic expression of the androgen receptor (AR) gene and loss of X-inactivation-specific transcript and trimethyl-histone H3 (Lys27) signals on X chromosomes, suggesting that both X chromosomes of the hiPS cells are in an active state. Importantly, normal dystrophin was expressed in multinucleated myotubes differentiated from a manifesting carrier of DMD-hiPS cells with XaXa pattern. AR transcripts were also equally transcribed from both alleles in induced myotubes. Our results indicated that the inactivated X chromosome in the patient’s fibroblasts was activated during reprogramming, and XCI occurred randomly during differentiation. [ABSTRACT FROM AUTHOR]

We report a convenient synthesis of carbazole-1,4-quinone alkaloid koeniginequinones A and B using a tandem ring-closing metathesis with the dehydrogenation reaction sequence under an O 2 atmosphere as an important step. Using this method, carbazole-1,4-quinones substituted at the 5-, 6-, 7-, and/or 8-positions have been synthesized. Moreover, 24 compounds, including koeniginequinones A and B, have been evaluated for their antiproliferative activity against HCT-116 and HL-60 cells, and the 6-nitro analog exhibited the most potent activity against both tumor cell types. [ABSTRACT FROM AUTHOR]

In this study, we achieved the total synthesis of carbazole alkaloid mukoenine A through a seven-step sequence involving the construction of a carbazole framework using the electrocyclization of a 6π-electron system including an allene intermediate as the key step. Subsequently, the synthesis of pyrano[3,2- a ]carbazole alkaloid girinimbine was achieved by the construction of the pyran ring via selenoetherification of the o-allylic phenol moiety of mukoenine A. [Display omitted] • The total synthesis of mukoenine A has been accomplished via a seven-step sequence. • Girinimbine was synthesized by the construction of the pyran ring via mukoenine A. • The carbazole framework was constructed by the allene-mediated electrocyclization. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) proteins are synthesized in the endoplasmic reticulum (ER), transported to the extracellular milieu through the secretory pathway, and assembled into an extracellular architecture. A previous study of ours showed that periostin, a secretory protein, interacts with fibronectin and is involved in ECM remodeling. Here we show that periostin played a role in fibronectin secretion from the ER. Co-immunoprecipitation and in situ proximity ligation assays revealed an interaction between periostin and fibronectin in the ER. Although accumulation of fibronectin was detected in the ER of fibroblastic C3H10T1/2 cells, forced expression of periostin in those cells decreased the accumulation of fibronectin in the ER, suggesting that periostin promoted the secretion of fibronectin. A substitution mutant of tryptophan at the position 65 to alanine in the EMI domain of periostin, which caused periostin to lose its ability to interact with fibronectin, did not decrease the accumulation. Furthermore, targeted disruption of periostin in mice caused the non-fibrillar and ectopic deposition of fibronectin in the periodontal ligament. Thus, these results demonstrate a subcellular role of periostin in promotion of fibronectin secretion from the ER. [ABSTRACT FROM AUTHOR]

Nanobubbles exist at solid–liquidinterfaces between purewater and hydrophobic surfaces with very high stability, lasting incertain cases up to several days. Not only semispherical but alsoother shapes, such as micropancakes, are known to exist at such interfaces.However, doubt has been raised as to whether or not the nanobubblesare gas-phase entities. In this study, surface nanobubbles at a purewater–highly ordered pyrolytic graphite (HOPG) interface wereinvestigated by peak force quantitative nanomechanics (PF-QNM). Multipleisolated nanobubbles generated by the solvent-exchange method werepresent on the terraced areas, avoiding the steps of the HOPG surface.Adjacent nanobubbles coalesced and formed metastable nanobubbles.Coalescence was enhanced by the PF-QNM measurement. We determinedthat nanobubbles can exist for a long time because of nanoscale contactangle hysteresis at the water–HOPG interface. Moreover, thehydrophilic steps of HOPG were avoided during coalescence, providingevidence that the nanobubbles are truly gas phase. [ABSTRACT FROM AUTHOR]

In this study, the total syntheses of 1,3,4-trisubstituted carbazole alkaloid clausamine E was accomplished via an eight-step sequence using construction of the 1,4-dioxygenated carbazole framework based on the cyclocarbonylation between 3-iodo-2-(prop-2-enyl)indole and CO (1 atm) in the presence of tributyl(vinyl)tin and a Pd catalyst. Image 1 • The total synthesis of clausamine E has been accomplished via an eight-step sequence. • Synthesis of 1,4-dioxygenated carbazoles by Pd-catalyzed cyclocarbonylation. • This method could be used as a versatile method to synthesize substituted carbazoles. [ABSTRACT FROM AUTHOR]

• The enantioselective total synthesis of (+)-asiaticumine A has been accomplished. • The construction of phenanthridine framework by MW-assisted electrocyclization. • The synthesis of 1,2-dihydroxyethyl moiety by Sharpless asymmetric dihydroxylation. • Its absolute configuration was determined to be S by Mosher's method. In this study, the first asymmetric enantioselective total syntheses of (+)-asiaticumine A (2) and its enantiomer were accomplished through a seven-step sequence using the bond formation between the C4a and N5 positions of the phenanthridine framework based on the microwave-assisted electrocyclization of cyclohexenylbenzaldoxime methyl ether as an aza 6π-hexatriene system followed by the Sharpless asymmetric dihydroxylation as the key step. In addition, the absolute configuration of natural (+)- 2 was determined to be S by Mosher's method. [ABSTRACT FROM AUTHOR]

Hepatitis E is a global public health problem. Ribavirin (RBV) and pegylated interferon alpha are currently administered to cure hepatitis E. Recently, in combination with RBV, sofosbuvir (SOF), an anti-hepatitis C virus nucleotide analog, is also given to patients with chronic hepatitis E. However, this combinatorial therapy sometimes fails to achieve a sustained virological response. In this study, we used 27 antiviral compounds, including 15 nucleos(t)ide analogs, for in vitro screening against a genotype 3 HEV strain containing a Gaussia luciferase reporter. RBV, SOF, 2′- C -methyladenosine, 2′- C -methylcytidine (2CMC), 2′- C -methylguanosine (2CMG), and two 4′-azido nucleoside analogs (R-1479 and RO-9187) suppressed replication of the reporter genome, while only RBV, SOF, 2CMC and 2CMG inhibited the growth of genotype 3 HEV in cultured cells. Although 2CMG and RBV (2CMG/RBV) exhibited a synergistic effect while SOF/RBV and 2CMC/RBV showed antagonistic effects on the reporter assay, these three nucleos(t)ide analogs acted additively with RBV in inhibiting HEV growth in cultured cells. Furthermore, SOF and 2CMG, with four interferons (IFN-α2b, IFN-λ1, IFN-λ2 and IFN-λ3), inhibited HEV growth efficiently and cleared HEV in cultured cells. These results suggest that, in combination with RBV or interferons, SOF and 2CMG would be promising bases for developing anti-HEV nucleos(t)ide analogs. • We tested inhibitory effects of 27 compounds on replication of an HEV reporter genome and growth of HEV in cultured cells. • 2′- C -methylguanosine (2CMG), 2′- C -methylcytidine (2CMC) and sofosbuvir (SOF) robustly suppressed HEV growth in cultured cells. • Ribavirin (RBV) with 2CMG suppressed replication of the reporter genome synergistically but antagonistically with 2CMC or SOF. • RBV with SOF, 2CMG, or 2CMC inhibited HEV growth additively and cleared HEV in cultured cells. • SOF or 2CMG with interferon-α2b, -λ1, -λ2, or -λ3 inhibited HEV growth additively and cleared HEV in cultured cells. [ABSTRACT FROM AUTHOR]

3-Iodo-2-propenylindoles (I) are easily prepared from corresponding indole-2-carbaldehydes and vinyl Grignard reagents. [ABSTRACT FROM AUTHOR]

Liquid cell electron microscopy is a useful technique for the observation of chemical, biological, and mechanical processes in liquids at nanometer-scale resolution. This study investigated the generation and growth of nanobubbles using the Fresnel fringe method, which enabled us to determine the location of bubble interface; the nanobubbles were induced in the 600-nm-thick water sample in the cell, by the electron beam. Nucleation occurred first at the solid–liquid interface in the upstream side of electron beam, and this was followed by second-group nucleation at the downstream-side interface; all of the stable nucleations occurred on the solid surfaces. The size of the nucleated bubbles at the moment they became visible depended on the magnification used in the electron microscope, and a higher-energy density in the electron beam induced larger bubbles. The underlying mechanism was also considered in this study. [ABSTRACT FROM AUTHOR]

The effect of the high order structure of an isotactic polypropylene (PP) composite on the resistivity of composites containing magnetically aligned Ni particles was studied. Only a small amount of particles needed to be added for the composite material to become conducting after heating while in a magnetic field. The Ni columns formed on applying the field were distorted by the formation of large PP spherulites. Changes to the crystallization process due to the addition of a nucleating agent gave rise to changes in the columnar structure, resulting in large changes in the resistivity of the composite material. Controlling the high order structure of the polymer matrix including its morphology is very important in order to be able to control the magnetically aligned Ni structure. [ABSTRACT FROM AUTHOR]

This study is the first to demonstrate the startup of a pilot-scale single-stage nitrogen removal using anammox and partial nitritation (SNAP) reactor utilizing marine anammox bacteria. A complete mixing type reactor, continuously fed with waste brine obtained from a natural gas plant (salinity 3%, NH 4 +-N 130–180 mg/L) and having an effective volume of 2 m3, achieved stable operation at temperatures of 20–30°C with a maximum nitrogen removal rate of 1.43 kg-N/m3/day. During the startup process, along with a small amount of seed sludge, granular sludge was additionally inoculated as a biomass carrier for the enrichment of ammonia oxidizing bacteria (AOB), followed by the enrichment of anammox bacteria. A mesh screen equipped at the outlet of the reactor facilitated the successful sludge retention in the reactor. Analysis of bacterial community composition indicated that Candidatus Scalindua was successfully enriched in the pilot SNAP reactor. These methods for stable sludge retention in the reactor greatly contributed to the startup of the first pilot-scale SNAP reactor using marine anammox bacteria. • Pilot scale SNAP reactor to treat waste brine was successfully started up for the first time. • Marine anammox bacteria affiliated to Candidatus Scalindua was enriched. • AOB granule formed precedingly provided favorable growth condition for anammox bacteria and worked as biomass carrier. • Application of mesh-screen contributed to the retention of SNAP sludge in the reactor. [ABSTRACT FROM AUTHOR]

Abstract Neutrophils are recruited to infection sites and kill bacteria by phagocytosis and reactive oxygen species (ROS) production. It has been reported that vacuoles are present in neutrophils that produce ROS and are present in large numbers in blood smears of patients with bacterial infections. The leukocyte differentiation function on the Sysmex automated hematology analyzer classifies leukocytes by flow cytometry. Particularly, side-scattered light is known to reflect the quantity of organelles. This study investigated the possibility of detecting vacuoles or invagination of cell membrane in neutrophils producing ROS using a hematology analyzer. Whole blood and polymorphonuclear (PMN) cell fractions were activated with phorbol myristate acetate (PMA) or formylmethionylleucylphenylalanine (fMLP) and analyzed using the Sysmex XE-2100 automated hematology analyzer. PMN fractions were morphologically analyzed with a confocal laser scanning microscope (CLSM), electron microscope (EM), and general-purpose conventional flow cytometer. In the white blood cell differentiation scattergram obtained in this analysis, a new cluster separate from the original neutrophil cluster appeared in the eosinophil area in an area of higher side-scattering (SSC) intensity. Flow cytometry analysis of the PMN fractions revealed that the cells in this new cluster were CD16b- and APF-positive, indicating that the cells were activated neutrophils that produced ROS. CLSM and EM findings revealed that ROS production occurred in the cytoplasm and that the activated neutrophils contained some vacuole-like structures of vacuoles or invagination of cell membrane. Vacuole-like S structures were found within the cytoplasm of neutrophils producing ROS. These neutrophils were detected as an independent cluster in the eosinophil area with higher SSC intensity than that shown by neutrophils in the traditional cluster on the white blood cell differentiation scattergram, likely because the vacuole-like structures increased the SSC intensity. Highlights • Neutrophils produce vacuoles in their cytoplasm during ROS production. • Vacuoles increase the side-scattering light intensity of neutrophils in flow cytometry. • Neutrophils producing ROS are detectable using a hematology analyzer. [ABSTRACT FROM AUTHOR]

Rat hepatitis E virus (ratHEV) genome has four open reading frames (ORFs: ORF1, ORF2, ORF3 and ORF4). The functions of ORF3 and ORF4 are unknown. An infectious cDNA clone (pUC-ratELOMB-131L_wt, wt) and its derivatives including ORF3-defective (ΔORF3) and ORF4-defective (ΔORF4) mutants, were constructed and their full-length RNA transcripts transfected into PLC/PRF/5 cells. ΔORF3 replicated as efficiently as wt in cells. However, ≤1/1000 of the number of progenies were detectable in the culture supernatant of ΔORF3-infected cells compared with wt-infected cells. ORF4 protein was not detectable in ratHEV-infected cells or in the liver tissues of ratHEV-infected rats. No marked differences were noted between wt and ΔORF4 regarding the viral replication and protein expression. ORF3 mutants with proline-to-leucine mutations at amino acids (aa) 93, 96 and/or 98 in ORF3 were constructed and transfected into PLC/PRF/5 cells. Wt and an ORF3 mutant with leucine at aa 98 (ORF3-L98) replicated efficiently (density 1.15–1.16 g/cm 3 ), while ORF3-L93 + L96 exhibited a decreased viral release and banded at 1.26–1.27 g/cm 3 , similar to ΔORF3. In conclusion, the ORF3 protein, especially its proline residues at aa 93 and 96, is essential for the release of membrane-associated ratHEV particles, and ORF4 is unnecessary for the replication of ratHEV. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) causes acute or chronic hepatitis in humans and can be transmitted via the fecal-oral route. Pigs are one of the main reservoirs for this infection. Sixty pigs, 4–5 months of age, on a swine herd in Japan had detectable anti-HEV IgG antibodies, and five (8.3%) of them had ongoing infection of genotype 3 HEV. Five HEV strains obtained from the viremic pigs shared 98.8–100% nucleotide identity, and one representative strain (swHE1606845), whose entire genomic sequence was determined in this study, differed by 14.1–19.6% from the reported HEV strains of subtypes 3a–3k and by 14.7–19.1% from other genotype 3 HEV strains whose subtypes have not yet been assigned. swHE1606845 showed a higher nucleotide p-distance value of ≥0.143 with the genotype 3 HEV strains of subtypes 3a–3k and ≥0.152 with other genotype 3 strains of unassigned subtypes. A SimPlot analysis revealed a lack of recombination events. These results indicate that swHE1606845 is a candidate member of a novel subtype of genotype 3. Further efforts to identify the swHE1606845-like novel strain are warranted to clarify the origin of this strain and to determine the complete nucleotide sequences of two additional swHE1606845-like strains for assigning a new subtype. [ABSTRACT FROM AUTHOR]

We demonstrate a general process for fabricating graphene nanoelectronic devices that have next several features: free-standing, micrometer-sized monolayer graphene with high quality, arbitrarily-shaped metallic electrodes or sensors. In contrast to the normal routes, a gas etching process is used to create a deep trench in silicon for suspending the whole graphene device in a much larger area. User-designed electrodes or sensors are fabricated on the suspended graphene at the same time for realizing multiple functions. In this work, a suspended gold nanofilm sensor is designed to measure the intrinsic electrical and thermal properties of graphene on site. The sensor serves as both electrode and precise resistance thermometer at the same time. By simply changing the metallic electrode shape and electrical circuit, the free-standing graphene can be made into different devices, such as single-molecule detector or nano-resonator. In order to test the robustness of graphene device, a high electrical current is applied to heat the graphene in vacuum until it breaks. The breakdown current density is measured to be 1.86 mA/μm. More importantly, this method is not only limited to graphene, but also can be applied to any other two-dimensional materials. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is recalcitrant to treatment as it is highly metastatic and rapidly progressive. While observing the behavior of human pancreatic BxPC-3 cells using an optical assay device called TAXIScan, we found that several synthetic pyrazole and pyrimidine derivatives inhibited cell migration. One such compound, 14–100 , inhibited metastasis of fluorescence-labeled BxPC-3 cells, which were transplanted into the pancreas of nude mice as a subcutaneously grown cancer fragment. Surprisingly, despite its low cytotoxicity, the compound also showed an inhibitory effect on cancer cell proliferation in vivo, suggesting that the compound alters cancer cell characteristics needed to grow in situ. Single-cell RNA-sequencing revealed changes in gene expression associated with metastasis, angiogenesis, inflammation, and epithelial-mesenchymal transition. These data suggest that the compound 14–100 could be a good drug candidate against pancreatic cancer. [Display omitted] • Synthesized pyrazole compound 14–100 inhibits pancreatic cancer cell growth in vivo. • Angiogenic ability and HSP70 expression is altered by 14–100. • Expression of CXCL8 was downregulated in the 14–100 treated cancer cells. • 14–100 has lower toxicity compared to the approved drug for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Concise syntheses of 9-methoxyellipticine, 3,4-dihydroellipticine (µ-alkaloid D), 1,2,3,4-tetrahydroellipticine, 2-methyl-1,2,3,4-tetrahydroellipticine, olivacine, 3,4-dihydroolivacine, (±)-guatambuine, and (±)-janetine were developed starting from hexatriene intermediates readily obtained by Pd-catalyzed tandem cyclization/cross-coupling reaction of indolylborates. The route enables the facile construction of pyrido[4,3- b]carbazoles by Cu-catalyzed 6π-electrocyclization and subsequent transformation of the pyridocarbazole intermediates into pyrido[4,3- b]carbazole alkaloids. [ABSTRACT FROM AUTHOR]

As a solid-state membrane with only one-atom thickness, nano-porous graphene has attracted intense attention in many critical applications. Here, the key challenge is to suspend a single-layer graphene (SLG) and drill nanopores with precise dimensions. Here, we report a simple and reliable route for making suspended fluorinated SLG with size-tunable nanopores. Our method consists of two steps: 1. a free-standing SLG ribbon was created between two gold pads after deep dry etching of silicon substrate by xenon difluoride. The SLG was fluorinated by 5–13%. Superior to the normal wet etching method, the dry etching process is much simpler and results in less hole-defect and edge deformation. A large area fluorinated SLG can be suspended due to the sufficient etch depth. 2. a focused ion beam was introduced to drill nanopores in graphene with an initial diameter around 20 nm. Followed by an electron beam induced carbon deposition, the diameter of nanopore was gradually decreased to sub-10 nm. By changing the deposition time, the size of nanopore can be precisely controlled. High-cost transmission electron microscope is no longer needed. Our method provides a simple and effective way for preparing free-standing fluorinated SLG ribbon suitable for single-molecule detection. [ABSTRACT FROM AUTHOR]

Thermoresponsive properties of poly(7-methacryloyloxycoumarin) ( P1a ) and its derivatives as homopolymers containing a photoreactive coumarin unit were systematically investigated. P1a showed a lower critical solution temperature (LCST)-type phase separation in dichloromethane, chloroform, and 1,1,2-trichloroethane. The temperature producing a 50% transmittance ( T c ) of 0.1 wt% P1a in distilled chloroform was 26 °C, while the T c value decreased to 21 °C in deuterated chloroform i.e., the deuterium isotope effect. The T c values in chloroform were adjustable from 28 to 57 °C by the introduction of the ethyleneoxy spacer and the substitution of α-methyl group by hydrogen. While the polymers containing 4-substituted coumarins were soluble in chloroform and dichloromethane from 0 °C to their boiling points. In the distilled chloroform solution, the coumarin units in P1a underwent a [2 + 2] cycloaddition and the transmittance at 500 nm decreased from 98% to 29% at 25 °C by a 180-s photoirradiation (326 mJ/cm 2 , emission band at 365 nm). [ABSTRACT FROM AUTHOR]

To accurately characterize the shape of interfacial nanobubbles using atomic force microscopy (AFM), we investigated the effect of wettability of the AFM tip while operating in the peak force tapping (PFT) mode. The AFM tips were made hydrophobic and hydrophilic by Teflon AF coating and oxygen plasma treatment, respectively. It was found that the measured base radius of nanobubbles differed between AFM height images and adhesion images, and that this difference depended on the tip wettability. The force curves obtained during the measurements were also different depending on the wettability, especially in the range of the tip/nanobubble interaction and in the magnitude of the maximum attractive force in the retraction period. The difference suggests that hydrophobic tips penetrate the gas/liquid interface of the nanobubbles, with the three phase contact line being pinned on the tip surface; hydrophilic tips on the other hand do not penetrate the interface. We then quantitatively estimated the pinning position and recalculated the true profiles of the nanobubbles by comparing the height images and adhesion images. As the AFM tip was made more hydrophilic, the penetration depth decreased and eventually approached zero. This result suggests that the PFT measurement using a hydrophilic tip is vital for the acquisition of reliable nanobubble profiles. [ABSTRACT FROM AUTHOR]

The O 4 -benzo[ c ]phenanthridine alkaloids exhibit potent antiproliferative activity against cancer cells, which is derived from their ability to inhibit of topoisomerase I and II. It has been reported that in the alkaloids a cationic quaternary ammonium atom, which results in resonance effects between ring A and B, is necessary for increased antiproliferative activity. These findings indicate the role of their substituents at ring A on inhibition of tumor cell proliferation. In the present study, we systematically assessed the cytotoxic activities of naturally occurring alkaloids and their derivatives containing various ring A substituents against two tumor cell lines, HCT-116 colon tumor cells and HL-60 promyelocytic leukemia cells. Among the cationic iminium alkaloids, which displayed more potent activity than the corresponding neutral derivatives, and the 7,8-oxygenated benzo[ c ]phenanthridine alkaloids, chelerythrine and NK109, exhibited stronger antiproliferative activity than the 8,9- and 9,10-oxygenated alkaloids. The activity of cationic iminium alkaloids could be correlated with the bond lengths of their ring A substituents and the electrostatic potentials of their ammonium molecules by DFT calculation. [ABSTRACT FROM AUTHOR]

The relationship between the chemical structure of PMMA-type polymers and the removal rate by hydrogen radicals was examined. Hydrogen radicals are known to have superior reduction ability and can be generated by decomposing H 2 on hot-wire surfaces. PMMA-type polymers, which are widely used as base polymers for ArF resist, have many variations with the difference in the substituents. The removal rate of the main chain scission type polymers was faster than that of the main chain cross-linking type polymers. In the main chain cross-linking type polymers, it is considered that reduction decomposition of polymer was inhibited apparently according to occurrence to simultaneously reduce decomposition by hydrogen radicals and main chain cross-link. The removal rate was slow in the case of the main chain scission type polymers with a benzene ring. We guessed that the polymer with a benzene ring was a stable structure by resonance stabilization of a benzene ring. We found that the removal rate was slow according to increasing bulkiness of α-side chain in the main chain scission type polymers. It is considered that etching resistance increases with increasing bulkiness of α-side chain of polymer. [ABSTRACT FROM AUTHOR]

Objective Serum uric acid (SUA) levels in humans are mainly regulated by urate transporters. Recent genome-wide association studies suggested that common variants of the human sodium-dependent phosphate cotransporter type 1 gene ( NPT1/SLC17A1) influence SUA. NPT1 has been reported to mediate urate transport, but its physiologic role in regulating SUA in humans remains unclear. Furthermore, the findings of replication studies of the relationship between NPT1 variants and gout have been inconsistent. The aims of this study were to investigate the effect of NPT1 on gout and to determine its physiologic role. Methods Five hundred forty-five male Japanese patients with gout and 1,115 male Japanese control subjects were genotyped for rs1165196 (I269T), a common missense variant in NPT1. Analyses of the association between rs1165196 and gout were then conducted, focusing especially on renal underexcretion (RUE) gout. Immunohistochemical analysis and functional analysis using Xenopus oocytes were also performed. Results Single-nucleotide polymorphism rs1165196 significantly decreased the risk of RUE gout (odds ratio 0.73, P = 0.031) but did not confer a risk for all gout ( P = 0.123). The immunohistochemical analysis revealed that human NPT1 is localized to the apical membrane of the renal proximal tubule. The functional analysis using Xenopus oocyte expression systems showed that rs1165196 increases NPT1-mediated urate export. Conclusion This study showed that NPT1 is a urate exporter located in the renal proximal tubule in humans, and that its common gain-of-function variant, rs1165196, causes RUE gout, a major subtype of gout. These findings enable us to deepen our understanding of the physiologic role of NPT1 as a renal urate exporter as well as its pathophysiologic role in gout. [ABSTRACT FROM AUTHOR]

Abstract: This paper discusses the removal of chemically amplified negative-tone i-line resist SU-8 using hydrogen radicals generated by the catalytic decomposition of H2 molecules in H2/N2 mixed gas (H2:N2 =10:90vol.%) using a tungsten hot-wire catalyzer. SU-8 resists with exposure doses from 7 to 280mJ/cm2 were removed by hydrogen radicals, although the SU-8 removal rate was independent of the exposure dose. The SU-8 removal rate increased with both substrate and catalyzer temperature, in addition to a decrease in the distance between the catalyzer and substrate. A high removal rate for cross-linked SU-8 with an exposure dose of 14mJ/cm2 of approximately 4μm/min was achieved with a catalyzer to substrate distance of 20mm, and catalyzer and initial substrate temperatures of 2400 and 165°C, respectively. [Copyright &y& Elsevier]

Boron neutron capture therapy (BNCT) is a cancer treatment with clinically demonstrated efficacy using boronophenylalanine (BPA) and sodium mercaptododecaborate (BSH). However, tumor tissue selectivity of BSH and retention of BPA in tumor cells is a constant problem. To ensure boron accumulation and retention in tumor tissues, we designed a novel polyethylene glycol (PEG)-based boron-containing lipid (PBL) and examined the potency of delivery of boron using novel PBL-containing liposomes, facilitated by the enhanced permeability and retention (EPR) effect. PBL was synthesized by the reaction of distearoylphosphoethanolamine and BSH linked by PEG with Michael addition while liposomes modified using PBL were prepared from the mixed lipid at a constant molar ratio. In this manner, novel boron liposomes featuring BSH in the liposomal surfaces, instead of being encapsulated in the inner aqueous phase or incorporated in the lipid bilayer membrane, were prepared. These PBL liposomes also carry additional payload capacity for more boron compounds (or anticancer agents) in their inner aqueous phase. The findings demonstrated that PBL liposomes are promising candidates to effect suitable boron accumulation for BNCT. [ABSTRACT FROM AUTHOR]

• Rat HEV ORF3 has the PxYPMP motif in place of the PSAP motif for human HEV ORF3. • Rat HEV utilizes multivesicular body sorting and exosomal pathway for its release. • Association of host factors Tsg101, Alix and Vps4A/B with rat HEV egress was noted. • Unlike human HEV ORF3, rat HEV ORF3 did not bind to Tsg101. • A 90-kDa host protein that could be a candidate alternative to Tsg101 was found. Recent reports have shown that rat hepatitis E virus (HEV) is capable of infecting humans. We also successfully propagated rat HEV into human PLC/PRF/5 cells, raising the possibility of a similar mechanism shared by human HEV and rat HEV. Rat HEV has the proline-rich sequence, PxYPMP, in the open reading frame 3 (ORF3) protein that is indispensable for its release. However, the release mechanism remains unclear. The overexpression of dominant-negative (DN) mutant of vacuolar protein sorting (Vps)4A or Vps4B decreased rat HEV release to 23.9 % and 18.0 %, respectively. The release of rat HEV was decreased to 8.3 % in tumor susceptibility gene 101 (Tsg101)-depleted cells and to 31.5 % in apoptosis-linked gene 2-interacting protein X (Alix)-depleted cells. Although rat HEV ORF3 protein did not bind to Tsg101, we found a 90-kDa protein capable of binding to wild-type rat HEV ORF3 protein but not to ORF3 mutant with proline to leucine mutations in the PxYPMP motif. Rat HEV release was also decreased in Ras-associated binding 27A (Rab27A)- or hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-depleted cells (to 20.1 % and 18.5 %, respectively). In addition, the extracellular rat HEV levels in the infected PLC/PRF/5 cells were increased after treatment with Bafilomycin A1 and decreased after treatment with GW4869. These results indicate that rat HEV utilizes multivesicular body (MVB) sorting for its release and that the exosomal pathway is required for rat HEV egress. A host protein alternative to Tsg101 that can bind to rat HEV ORF3 should be explored in further study. [ABSTRACT FROM AUTHOR]

Cu-catalyzed 6π-electrocyclization of triene-substrates of type (I) provides a facile access to pyrido[4,3-b]carbazoles, which represent advanced intermediates for the construction of various ellipticine and olivacine alkaloids. [ABSTRACT FROM AUTHOR]

Graphene oxide (GO) is hydrophilic and swells significantly when in contact with water. Here, we investigate the change in thickness of multilayer graphene oxide membranes due to intercalation of water, via humidity-controlled observation in an environmental scanning electron microscope (ESEM). The thickness increases reproducibly with increasing relative humidity. Electron energy loss spectroscopy (EELS) reveals the existence of water ice under cryogenic conditions, even in high vacuum environment. Additionally, we demonstrate that freezing then thawing water trapped in the multilayer graphene oxide membrane leads to the opening up of micron-scale inter-lamellar voids due to the expansion of ice crystals. [ABSTRACT FROM AUTHOR]