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Here, we report synthesis and properties of a di-ruthenium acetylide molecular wire having a diethynylporphyrinatomanganese linker, and the effect of the coordination of electron-donor molecules to...

Aim Cancer‐associated fibroblasts (CAFs) generated by bone marrow‐derived mesenchymal stem cells (BM‐MSCs) play an important role in cancer progression. In this study, we investigated the relationships of BM‐MSCs and CAFs in resected gastric cancers with the clinicopathological factors of patients. Methods We analyzed 120 gastric cancer patients who underwent gastrectomy. Immunostaining was performed with an anti‐CD271 antibody (BM‐MSCs) and anti‐α‐smooth muscle actin (αSMA) antibody (CAFs). Staining intensity was used to divide patients into low and high expression groups. Observation sites in cancer tissues were invasive, central, and whole portions. Results Expression of αSMA was significantly related to depth of tumor invasion (T), lymph node metastasis (N), lymphatic invasion (ly), venous invasion (v), and stage. Expression of CD271 was significantly related to v, stage, stromal volume, and tumor infiltration pattern (INF). Overall survival (OS) of the high expression group was significantly lower than that of the low expression group for both αSMA and CD271. Multivariate analysis showed that N, αSMA (whole), and CD271 (invasive) were independent prognostic factors. Conclusions Cancer‐associated fibroblasts and BM‐MSCs are related to the progression, invasion, and prognosis of gastric cancer and may be therapeutic targets of gastric cancer., We immunohistochemically examined bone marrow‐derived mesenchymal stem cells and cancer‐associated fibroblasts in gastric cancer tissues and obtained results indicating that they were associated with tumor infiltration and stroma, and closely related to prognosis.

Recently, we developed self-assembled electret (SAE)-based vibrational energy generator (VEG) which can generate electrical power from ambient vibrations. An advantage of the device is that any charging process is not required for making electret, that is, surface potential (V sp ) of SAE naturally appears only by vacuum deposition. This is because the V sp originates from spontaneous orientation of polar molecules such as Alq 3 and TPBi. Thus, to increase output power of SAE-VEG, enhancement of order parameter of the molecule, $\langle \cos \theta \rangle$, is required. In this study, we prepared TPBi-based SAE films with various deposition rate (r dep ). We found that the V sp becomes 1.8 times larger in the case of high r dep of 4.0 A/s, suggesting that molecular orientation can be controlled by r dep . This result indicates that further enhancement of output power in SAE-VEG can be realized through optimization of fabrication process of SAE.

Self-assembled electrets (SAEs), in which polar molecules such as Alq 3 and TPBi are spontaneously ordered by vapor deposition, are promising materials for vibrational energy generators (VEGs). SAEs can simplify fabrication process of VEGs because the charging process, e.g. corona charging, is not required; however, SAEs are sensitive for light irradiation because charge carriers are generated by exciton dissociation, leading to compensation of polarization charge on the SAE surface. In order to restrict charge generation, in this study, the dye molecule is doped into SAE having a wider optical gap than that of dye molecule. In the doped SAE, exciton energy is transferred to the dye, resulting in exciton quenching. In this work, we doped Alq$_{3}(2.4$ vol%) to TPBi which has a wide optical gap, and stability of VEG composed of the doped film was evaluated during light irradiation. We demonstrate that the retention time of 50% loss in the device was 2.6 times longer than that of neat TPBi-based VEG. This result suggests that the application of doped SAE is quite useful to realize long-lived SAE-based VEG.

Well-defined 9,10-bis(di(p-tert-butylphenyl)amino)anthracene serves as a photocatalyst for radical fluoroalkylation under visible light irradiation. The diarylamine (Donor)–anthracene (π conjugated system)–diarylamine (Donor) scaffolds are easily accessed by typical palladium-catalyzed cross-coupling protocols of the corresponding halogenated anthracenes with various lithium diarylamides. The anthracene-based photocatalyst exhibits high reducing power, leading to generation of versatile fluoroalkyl radicals such as tri- and difluoroethyl and tri- and difluoromethyl radicals from the corresponding electron-accepting precursors. Catalyst design strongly influences the absorption capability of visible light and stability toward redox stimuli. The detailed mechanistic studies on the metal-free photocatalytic amino-trifluoroethylation of styrene with diphenyl(2,2,2-trifluoroethyl)sulfonium trifluoromethanesulfonate suggest that the reaction proceeds via catalytic radical processes rather than radical chain pro...

The Corynebacterium glutamicum R grtA (cgR_2936), grtB (cgR_2934) and grtC (cgR_2933) genes were identified as paralogs encoding glutamine-rich toxic proteins. We also identified a new antisense small RNA AsgR (antisense sRNA for grtA) that overlaps the 3' end of the grtA gene. Single over-expressions of grtA, grtB and grtC resulted in complete inhibition of Escherichia coli cell growth. This growth was rescued by co-expression of AsgR. Similar effects were observed in C. glutamicum, although the toxicities of these proteins were moderate. Inhibition of AsgR transcription resulted in increased levels and prolonged half-lives of grtA, grtB and grtC mRNAs. We also found that the expression levels of grtA, grtB and grtC were increased in an RNase III deletion mutant. Primer extension analysis revealed the RNase III cleavage site to be in the 3' untranslated region (3'-UTR) of the grtA mRNA. The expression levels of grtA, grtB and grtC were increased after exposure to several stresses, including heat shock, treatment with penicillin G, lysozyme or H2 O2 . The deletions of grtABC and asgR genes resulted in decreased survival rate under several stresses. These results indicate that GrtABC and AsgR constitute a type I toxin-antitoxin-like system in C. glutamicum.

In this paper, a novel application of a robust controller for an electronic governor of a small gas engine generator is presented. There are a few studies regarding the fluctuations in the concentration of bio-methane fuel and load fluctuation of a generator using an approximately 1-kW small gas engine generator. For a relatively small-scale local-production-type energy circulation system, such as the gas energy from a Tambo (GET) system, it is necessary to develop a small gas engine generator that can use the generated unpurified bio-methane gas to accommodate the load fluctuation. The GET system is a bio-methane gas production system, utilizing the sustainable resources from a paddy field, without requiring any distinct auxiliary facilities. We have examined the bio-methane gas produced from the GET system as the fuel of a small gas engine generator, which can supply electric energy and thermal energy to a greenhouse. We have studied the application of a robust engine controller by combining a model matching controller and an optimal observer (MM_OBSV controller) with the electronic governor of the small gas engine generator. The results indicate that the control system is adapted for the input disturbance (load fluctuation and modeling error), with the MM_OBSV controller embedded in the electronic governor of the small gas engine generator.

The synthesis and photoluminescence properties of three-coordinate Au(i) complexes with rigid diphosphine ligands LMe {1,2-bis[bis(2-methylphenyl)phosphino]benzene}, LEt {1,2-bis[bis(2-ethylphenyl)phosphino]benzene}, and LiPr {1,2-bis[bis(2-isopropylphenyl)phosphino]benzene} are investigated. The LMe and LEt ligands afford two types of complexes: dinuclear complexes [μ-LMe(AuCl)2] (1d) and [μ-LEt(AuCl)2] (2d) with an Au(i)-Au(i) bond and mononuclear three-coordinate Au(i) complexes LMeAuCl (1) and LEtAuCl (2). On the other hand, the bulkiest ligand, LiPr, affords three-coordinate Au(i) complexes, LiPrAuCl (3) and LiPrAuI (4), but no dinuclear complexes. X-ray analysis suggests that both 3 and 4 possess a highly distorted trigonal planar geometry. Moreover, luminescence data reveal that at room temperature, 3 and 4 exhibit yellow-green thermally activated delayed fluorescence in the crystalline state with maximum emission wavelengths at 558 and 549 nm, respectively. The emission yields are close to unity. Quantum chemical calculations suggest that the emission of 4 originates from the (σ + X) → π* excited state that possesses strong intraligand charge-transfer character. The luminescent properties of four-coordinate Au(i) complex (5) possessing a tetrahedral geometry are discussed on the basis of the emission spectra and decay times measured in a temperature range of 309-77 K.

Slug flow is segmented droplets where internal convection occurs. The internal convection is useful for efficient mixing of their contents when they are used as microreactors. The segmentation is also useful for recording of temporal changes in biological samples such as cells and animals. However, methods to store the droplets separately, which are necessary for precise chemical analysis, are not well developed. Methods with simple structures and controls are required for storing many droplets in the first-come-first-store manner. Passive microvalves allow for prearranged flow without any controls using simple microstructures. To store the droplets one-by-one for precise analysis, we designed an automatic microfluidic device using hydrophobic passive microvalves. The valves are based on capillary forces and have different burst pressures. Using this device, each droplet was automatically stored in a different reservoir.

A dinuclear (μ-hydroxo)(μ-pyrazolato)dicobalt(II) complex with hydrotris(3,5-diisopropyl-1-pyrazolyl)borate (TpiPr), [CoII(TpiPr)]2(μ-OH)(μ-Pz) (8), was synthesized and structurally characterized, showing that the metal-hydroxide moiety acts as a nucleophile toward 4-nitrophenyl acetate and CO2, similarly to metalloenzymes. The X-ray analysis revealed that the complex 8 has a symmetry plane and that its two cobalt ions present distorted five-coordinated structures, that is, each of them is coordinated to one oxygen atom from the bridging μ-OH ligand and four nitrogen atoms from the TpiPr ligand and the bridging μ-Pz ligand. The Co1–O1 (1.966(2) A) and Co1–N3 (2.085(4) A, where N3 is from μ-Pz) bond lengths are shorter than the Mn–O (2.075(5) and 2.047(5) A) and Mn–N (2.160(5) and 2.215(6) A) ones of the previously reported dimanganese(II) analog complex due to the stronger Lewis acidity of cobalt(II). Upon reaction of the complex 8 with CO2, a dinuclear cobalt(II) μ-carbonato complex 7 was obtained. In case of reaction with 4-nitrophenyl acetate, a mononuclear cobalt(II) 4-nitrophenoxo complex with 3,5-diisopropylpyrazole (PzH) on the cobalt(II) center, [CoII(PzH)(TpiPr)(OC6H4-4NO2)] (9), was generated, thus serving as an important model for hydrolase enzyme.

This paper is concerned with the attraction–repulsion chemotaxis system with superlinear logistic degradation, u t = Δ u − χ ∇ ⋅ ( u ∇ v ) + ξ ∇ ⋅ ( u ∇ w ) + λ u − μ u k , x ∈ Ω , t > 0 , 0 = Δ v + α u − β v , x ∈ Ω , t > 0 , 0 = Δ w + γ u − δ w , x ∈ Ω , t > 0 , under homogeneous Neumann boundary conditions, in a ball Ω ⊂ R n ( n ≥ 3 ), with constant parameters λ ∈ R , k > 1 , μ , χ , ξ , α , β , γ , δ > 0 . Blow-up phenomena in the system have been well investigated in the case λ = μ = 0 , whereas the attraction–repulsion chemotaxis system with logistic degradation has been not studied. Under the condition that k > 1 is close to 1, this paper ensures a solution which blows up in L ∞ -norm and L σ -norm with some σ > 1 for some nonnegative initial data. Moreover, a lower bound of blow-up time is derived.

要介護者が急速に増加する中、介護に携わる人の着用する介護ユニフォームは、介護業務のしやすさなどの機能性とともに、介護現場の雰囲気づくりにおいても考慮すべき重要な課題である。本報では、老人福祉施設の中でも養護老人ホーム、特別養護老人ホームの現場で働いているスタッフ、および介護の現場経験はないが、介護に対するイメージのみを持っている被験者を対象群とし、介護サポートに適する望ましい介護ユニフォームのトップス（上衣）に対するデザインと色の視覚的効果について検討した。「ボタン式ポケット付きポロシャツ」に対し「親しみやすさ」、「落ち着き」、「好き」と評価された。一方、介護ユニフォームの色について、非スタッフでは白が評価され、清潔感や医療、介護というイメージから評価されたと考えられる。全体的に白、サーモンピンク、黄緑、ベージュ、青などの評価が高く、同色系でも明度の高くて彩度が低い色の評価が高い結果となった。

Background and objectives: Massive postpartum hemorrhage (PPH) is the most common cause of maternal death worldwide. A massive transfusion protocol (MTP) may be used to provide significant benefits in the management of PPH, however, only a limited number of hospitals use MTP protocol to manage massive obstetric hemorrhages, especially in Japan. This study aimed to assess the clinical outcomes in patients in whom MTP was activated in our hospital. Materials and Methods: We retrospectively reviewed the etiology of PPH, transfusion outcomes, and laboratory findings among the patients treated with MTP after delivery in our hospital. Results: MTP was applied in 24 cases (0.7% of deliveries). Among them, MTP was activated within 2 h of delivery in 15 patients (62.5%). The median estimated blood loss was 5017 mL. Additional procedures to control bleeding were performed in 19 cases, including transarterial embolization (18 cases, 75%) and hysterectomy (1 case, 4.2%). The mean number of units of red blood cells, fresh frozen plasma, and platelets were 17.9, 20.2, and 20.4 units, respectively. The correlation coefficients of any two items among red blood cells, fresh frozen plasma, platelets, blood loss, and obstetrical disseminated intravascular coagulation score ranged from 0.757 to 0.892, indicating high levels of correlation coefficients. Although prothrombin time and activated partial thromboplastin time levels were significantly higher in the &lt, 150 mg/dL fibrinogen group than in the ≥150 mg/dL fibrinogen group at the onset of PPH, the amount of blood loss and blood transfusion were comparable between the two groups. Conclusions: Our MTP provides early access to blood products for patients experiencing severe PPH and could contribute to improving maternal outcomes after resuscitation in our hospital. Our study suggests the implementation of a hospital-specific MTP protocol to improve the supply and utilization of blood products to physicians managing major obstetric hemorrhage.

These notes aim to provide a deeper insight on the specifics of two articles dealing with chemotaxis models with nonlinear production. More precisely, we are referring to the papers “Boundedness of solutions to a quasilinear parabolic–parabolic chemotaxis model with nonlinear signal production” by Tao et al. (2019) [2] and “Boundedness for a fully parabolic Keller–Segel model with sublinear segregation and superlinear aggregation” by Frassu and Viglialoro (2021) [1] . These works, independently published in these last years, present results leaving open room for further improvement. Indeed, in the first a gap in the proof of the main claim appears, whereas the cornerstone assumption in the second is not sharp. In these pages we give a more complete picture to the relative underlying comprehension.

Fatigue strength of Ni-based superalloy 718 was investigated relative to shear-mode crack-growth thresholds, to evaluate the influence of crack-opening/-closing stresses perpendicular to shear-mode crack-planes. The impact of precipitation-hardening was also examined. Using solution-treated and precipitation-hardened materials, three different types of fatigue tests were performed: (i) push–pull; (ii) pure-torsion; (iii) torsion with superposed static tension. All tests revealed non-propagation of small, shear-mode cracks, while confirming the negligible impact of precipitation-hardening on shear-mode crack-growth threshold. Additionally, crack-opening/-closing stresses were determined to only imperceptibly alter shear-mode resistance. Based on these findings, a novel strategy was proposed to quantify the alloy’s fatigue strength.

Here we report properties of thiophene-rich, acetylide-type mono-, di- and tri-nuclear ruthenium molecular wires 1–4, which are prepared by rationally designed coupling of vinylidene intermediates. Electrochemical analysis of 1–3 reveals fully reversible redox waves, the numbers of which are equal to those of the ruthenium fragments. Spectroelectrochemical analysis of 2 and 3 reveals the clear step-by-step oxidation processes. Analysis of NIR absorption bands reveals that the monocationic species 2+ and 3+ are highly charge-delocalized species, which are further supported by DFT and TD-DFT calculations of their model complexes.

Purpose The aim of this study is to present an easy and quick technique for embolization of the inferior mesenteric artery (IMA) during endovascular aneurysm repair (EVAR). Technique We performed IMA embolization using a conventional EVAR device alone with the femoral artery approach during EVAR, which has not been reported previously. First, a 16F or 18F DrySeal Sheath is inserted from the femoral artery into the site around the IMA. Second, cannulation is performed in the IMA with an angiography catheter having a 0.038-inch inner lumen that is used for gate cannulation during EVAR. Third, IMA embolization is performed using the Amplatzer Vascular Plug 4 (AVP4). The use of the DrySeal Sheath facilitates cannulation of the IMA, and its combination with a stent-graft balloon allows the AVP4 to be placed at the root of the IMA without deviation of the catheter. The success rate of the procedure was 90.9% (30/33 cases). The median procedure time was 11.6 min. No complications due to IMA embolization were noted. Conclusion This procedure enables safe and quick placement of the AVP4 in the IMA using the catheter insertion approach from the femoral artery, which has been conventionally regarded as difficult.

近年、フリースクールの制度化を目指す動きが活発化し、2016 年には「教育機会確保法」が成立したが、フリースクールの制度化をめぐってはさまざまな意見がある。本稿では、フリースクールの制度化に先行してフリースクールに言及した政府の有識者会議の報告書や、制度化に反対する障害者運動の主張を検討し、論争において何が焦点化されているかを考察した。政府の有識者会議が主に人的資本の有効活用という観点からフリースクールの制度化を捉えているのに対し、「普通学級」へのインクルージョンを主張してきた障害者運動は「分離・別学体制」の強化と捉えている。そして、さまざまな批判があるなかで、NPO 法人フリースクール全国ネットワーク代表理事の奥地圭子は、不登校の子どもの権利を保障するという観点から、フリースクールの制度化を推進していることをインタビューにより明らかにした。

講演：山田 潤 , 編集：田中 佑弥

By taking advantage of three-terminal capacitance-voltage (TT-CV) measurement, we investigated a formation of trapped charge in pentacene(Pn)-based organic field-effect transistors (OFETs) during the bias stress measurement. The shift of the turn-on voltage in transfer curve correlated well with the increase of trapped charge estimated from TT-CV curves. Moreover, TT-CV measurement revealed that the trapped charges were distributed inhomogeneously at the vicinity of the pentacene/insulator interface, indicating that the current does not obviously affect their formation. Thus we suggested that the trapped charges are formed by keeping Pn molecules as unstable cation (hole state) by the prolonged bias stress.

The resection of the medial and lateral pyriform sinus was associated with post-operative voice impairment after TOVS. Scar contracture around the cricoarytenoid joint lead to arytenoid fixation toward lateral position, and this wound healing process caused insufficient glottis closure. Although oncological and functional outcomes of TOVS was satisfactory, surgeons should mention the risk of post-operative voice impairment in pre-operative counseling.Transoral surgery is a minimally invasive treatment option for hypopharyngeal and supraglottic cancer. Post-operative vocal function was satisfactory in most cases, but in some cases vocal cord was fixed and occasionally voice impairment persists.Vocal function of 55 patients who underwent transoral videolaryngoscopic surgery (TOVS) for hypopharyngeal and supraglottic cancers was evaluated by the GRBAS perceptive scale, aerodynamic tests and acoustic analyses, and the Voice Handicap Index questionnaire. The risk factors for voice impairment were identified.Voice impairment (G score ≧2) was found in 16 cases (29.1%). Univariate analysis revealed that the resection of medial and lateral pyriform sinus (p = .0018) and neck dissection (p = .0421) were associated with post-operative voice impairment. Multivariate analysis revealed that the resection of medial and lateral pyriform sinus (p = .0021) was associated with post-operative voice impairment.

Recent developments of single-molecule conductance measurements allow us to understand fundamental conducting properties of molecular wires. While a wide variety of organic molecular wires have been studied so far, inorganic and organometallic molecular wires have received much less attention. However, molecular wires with transition-metal atoms show interesting features and functions distinct from those of organic wires. These properties originate mainly from metal-ligand dπ-pπ interactions and metal-metal d-d interactions. Thanks to the rich combination of metal atoms and supporting ligands, frontier orbital energies of the molecular wires can be finely tuned to lead to highly conducting molecular wires. Moreover, the unique electronic structures of metal complexes are susceptible to subtle environmental changes, leading to potential functional molecular devices. This article reviews recent advances in the single-molecule conductance study of inorganic and organometallic molecular wires.

A material with a wide energy gap, 3,4-di(9H-carbazol-9-yl)benzonitrile (2CzBN), was synthesized and applied in organic light-emitting diodes (OLEDs). Pure blue electroluminescence with a peak wavelength of 436 nm and Commission Internationale de l'Eclairage (CIE) coordinate of (0.160, 0.084) were obtained for an OLED containing 2CzBN as an emitter, although its external emission efficiency was limited to around 1% because of the lack of thermally activated delayed fluorescence (TADF) activity. In contrast, a highly efficient TADF-based OLED was obtained when 2CzBN was used as a host instead of an emitter by taking advantage of the high triplet energy (2.92 eV) and unexpected electron transport capability of 2CzBN.

Over the past few decades, several molecular cages, hosts and nanoporous materials enclosing nanometre-sized cavities have been reported1–5, including coordination-driven nanocages6. Such nanocages have found widespread use in molecular recognition, separation, stabilization and the promotion of unusual chemical reactions, among other applications3–10. Most of the reported nanospaces within molecular hosts are confined by aromatic walls, the properties of which help to determine the host–guest behaviour. However, cages with nanospaces surrounded by antiaromatic walls have not yet been developed, owing to the instability of antiaromatic compounds; as such, the effect of antiaromatic walls on the properties of nanospaces remains unknown. Here we demonstrate the construction of an antiaromatic-walled nanospace within a self-assembled cage composed of four metal ions with six identical antiaromatic walls. Calculations indicate that the magnetic effects of the antiaromatic moieties surrounding this nanospace reinforce each other. This prediction is confirmed by 1H nuclear magnetic resonance (NMR) signals of bound guest molecules, which are observed at chemical shift values of up to 24 parts per million (ppm), owing to the combined antiaromatic deshielding effect of the surrounding rings. This value, shifted 15 ppm from that of the free guest, is the largest 1H NMR chemical shift displacement resulting from an antiaromatic environment observed so far. This cage may thus be considered as a type of NMR shift reagent, moving guest signals well beyond the usual NMR frequency range and opening the way to further probing the effects of an antiaromatic environment on a nanospace. The construction of a self-assembled nanocage composed of four metal ions and six antiaromatic walls is demonstrated, and the effect of antiaromaticity on the host–guest properties is investigated.

Objective The aim of this study was to evaluate the efficacy and safety of local steroid injections to prevent scar contracture after transoral videolaryngoscopic surgery (TOVS) in hypopharyngeal cancer patients. Methods Patients were enrolled in this study if they had received a local steroid injection during TOVS and had attended an outpatient clinic after at least three months. All patients were being treated for hypopharyngeal cancer and received a single session of triamcinolone acetonide, injected using a 21-gage needle. Retrospective chart reviews were performed, and the degree of scar contracture, pharyngeal stenosis, vocal fold movements, and adverse events were evaluated. Scar contracture was assessed using a scoring system, which compared the endoscopic findings of treatment and matched pair control groups. Results A total of 20 patients received local steroid injections during TOVS and were enrolled in the treatment. Scar contracture was seen in 14 patients (70%); however, the degree of scar contracture was significantly decreased when compared to control cases. Vocal fold immobility was observed in five patients, but no pharyngeal stenosis was noted. Adverse effects, such as postoperative laryngeal chondritis or cervical spondylitis, were seen in three patients who had previously been treated with resection to the muscularis propria or definitive irradiation. Conclusion Local steroid injection during TOVS significantly reduced the degree of postoperative scar contracture. However, caution should be used when treating with local steroid injection during TOVS, as this may complicate wound healing in patients who have already received treatment.

Fusarium species are traditionally grouped into type A and type B trichothecene producers based on structural differences in the mycotoxin they synthesize. The type B trichothecene-producing Fusarium graminearum strains are further divided into 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), and nivalenol (NIV) chemotypes. The former two chemotypes, collectively termed a deoxynivalenol (DON) chemotype, evolved from a NIV chemotype by inactivation of FgTri13, which encodes trichothecene C-4 hydroxylase, during the evolutionary process. Despite stable overexpression of FgTri13, however, both 3-acetylnivalenol (3-ANIV) and 3-ADON accumulate equally in shake flask culture of a transgenic 3-ADON chemotype. In this study, we investigated why the "3-ANIV chemotype" could not be obtained using this strategy. When analysis was extended to the transgenic NIV chemotype, in which FgTri7 C-4 acetylase gene was disrupted and FgTri8 deacetylase gene was replaced with the 3-ADON chemotype's orthologue, C-4 unoxygenated 3-ADON, as well as C-4 oxygenated 3-ANIV, accumulated as the end product. A feeding experiment with an ΔFgtri5ΔFgtri3 double gene disruptant, a trichothecene non-producing mutant unable to acetylate C-15 of the trichothecene ring, revealed the importance of the 15-O-acetyl group for efficient C-4 hydroxylation of DON-type trichothecenes. This implies that traditional DON and NIV chemotype diversification is not solely explained by FgTri13, but is also explained by the function of the FgTri8 trichothecene deacetylase gene. None of the crude cell extracts from existing chemotypes showed highly specific C-15 deacetylation activity against 3,15-diacetylnivalenol (3,15-diANIV) without deacetylating C-15 of the C-4 unoxygenated earlier intermediate, 3,15-diacetyldeoxynivalenol. Thus, an unnatural Fusarium trichothecene, 3-ANIV, could only be synthesized as part of a mixture with 3-ADON, unless the esterase encoded by FgTri8 evolves to act on the 15-O-acetyl of 3,15-diANIV with high specificity. We also explain why the transgenic "15-ANIV chemotype", which can be generated through functional inactivation of FgTri7, uses an engineered pathway via 3,15-diANIV, but not 15-ADON, to generate 15-ANIV. Tri genes appear to evolve continuously, and altered functions of trichothecene pathway enzymes result in the generation of new trichothecenes, such as NX-2 and NX-3, which have been recently discovered in field isolates of F. graminearum. As recombination of FgTri8 between existing F. graminearum isolates could give rise to a strain that produces mixtures of DON and NIV-type trichothecenes, it may also be noteworthy to monitor the emergence of a field isolate that invalidates traditional chemotype classification.

We report a resected case of basaloid squamous cell carcinoma (BSC). BSC is a rare type of malignant lung tumor. A 79-year-old woman had a 13 mm tumor in the left upper lobe on chest computed tomography (CT). On fluorodeoxyglucose-position emission tomography (FDG-PET), the tumor showed the accumulation of FDG with an SUVmax of 14.7. A left upper lobectomy with lymph node dissection was performed by video-assisted thoracoscopic surgery. The pathological diagnosis was BSC (pT2aN0M0, stage IB). There was no recurrence following lung cancer resection for 12 months. BSC is generally poor prognosis.

Billions of people are using smartphones everyday and they often face problems and troubles with both the hardware as well as the software. Such problems lead to frustrated users and low customer satisfaction. Developing an automatic machine learning-based solution that would detect that the user has a problem and would engage in troubleshooting has the potential to significantly improve customer satisfaction and retention. Here, we design and implement a system that based on the user's smartphone activity detects that the user has a problem and requires help. Our system automatically detects a user has a problem and then helps with the troubleshooting by recommending possible solutions to the identified problem. We train our system based on large-scale customer support center data and show that it can both detect that a user has a problem as well as predict the category of the problem (89.7% accuracy) and quickly provide a solution (in 10.4ms). Our system has been deployed in commercial service since January, 2019. Online evaluation result showed that machine learning based approach outperforms the existing method by approximately 30% regarding the user problem solving rate.

Standardized allergen extracts are recommended for allergen immunotherapy. Since 2015, for patients with house dust mite allergies, we used a standardized house dust mite extract for subcutaneous immunotherapy, rather than non-standardized house dust extract. This study hypothesizes that standardized house dust mite extract (HDM group) was superior to non-standardized house dust extract (HD group) for subcutaneous immunotherapy.In this noninterventional, retrospective study, we enrolled patients with allergic rhinitis and sensitization to house dust mites. The HDM group (27 patients) received subcutaneous standardized extract immunotherapy since 2015, and the HD group (37 patients) received non-standardized extracts before 2015. We assessed the safety and efficacy between the two groups; the safety was assessed by the systemic reaction (SR) rate. The efficacy was assessed by reductions in the allergic rhinitis symptom-medication score, and the asthma treatment score, over a year.The SR rate of the HDM group (44%) was significantly higher than that (14%) of the HD group. The HDM group displayed a 57% reduction in the allergic rhinitis symptom-medication score, which was markedly higher than the 40% reduction observed in the HD group. In the standardized group, there was a 66% reduction occurred in the asthma medication score, markedly higher than the 36% reduction observed among patients in the HD group.Standardized house dust mite extract was more effective than non-standardized house dust extract for subcutaneous immunotherapy; however, the establishment of safer methods is warranted.

Backgroud Among various myocyte-derived bioactive molecules (myokines), β-aminoisobutyric acid (BAIBA) is a unique myokine that attenuates skeletal muscle insulin resistance and inflammation, increases browning of white adipose tissue, and enhances hepatic fatty acid oxidation, resulting in upregulated energy expenditure of the whole body. In the present study, we investigated the effects of BAIBA on the vascular endothelial cell function. Methods The mRNA levels of proinflammatory molecules, antioxidants, and their related transcription regulators were examined by quantitative RT-PCR in BAIBA-treated human aortic or umbilical vein endothelial cells (HAEC or HUVEC, respectively), with or without tumor necrosis factor (TNF)-α stimulation. The protein expression and phosphorylation of AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) were determined by Western blot analysis. Results BAIBA pretreatment significantly suppressed the mRNA levels of the adhesion molecules in the TNF-α-stimulated HAEC and HUVEC. BAIBA treatment significantly increased the mRNA levels of antioxidant molecules, catalase, superoxide dismutases, thioredoxin, and gamma-glutamylcysteine ligases, together with mitochondrial biogenesis-related molecules, nuclear respiratory factor 1, and mitochondrial transcription factor A. In addition, BAIBA treatment significantly increased the transcription factors that regulated these genes [i.e., peroxisome proliferator-activated receptor (PPAR)-δ, PPAR-γ, estrogen-related receptor α (ERRα), and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1β]. Adenovirus-mediated PGC-1β overexpression significantly increased the mRNA levels of all antioxidant molecules. The phosphorylation levels of AMPK and eNOS were unaltered by BAIBA. Conclusions In vascular endothelial cells, BAIBA had antiatherogenic effects through the PGC-1β−ERRα/PPAR-δ and PPAR-γ pathway. This can explain the beneficial effects of exercise on vascular endothelial function.

Objective Transoral videolaryngoscopic surgery (TOVS) was developed as a non-robotic procedure for en bloc laryngo-hypopharyngeal cancer resection. Straight devices had been used for this procedure, however, some cases had difficulty to reach the lesions especially in hypopharyngeal area. To overcome this problem, technical updates to facilitate transoral manipulation were developed and long term oncological and functional results were analyzed. Methods Surgical indications were Tis, T1, T2 and selected T3 cases. In advanced T3 or T4 lesions, neoadjuvant chemotherapy was performed before surgery. Radiation failure cases (rT1 and rT2) were also indicated for TOVS. Resectable nodal involvement can be managed by combination of neck dissection. Ninety hypopharyngeal and 25 supraglottic cancer cases were retrospectively reviewed for survival analyses. In fresh hypopharyngeal cancer, 51 Stage 0–II disease and 32 Stage III-IV disease were included. In supraglottic cancer, 11 Stage I–II disease and 9 Stage III-IV disease were included. Twelve radiation failure cases were analyzed separately. As new devices, malleable forceps and malleable suction coagulator were introduced to reach the whole laryngo-hypopharynx. New curved blades for the FKWO retractor were developed and these were applied for difficult hypopharyngeal exposure cases by conventional blades. Swallowing functional outcome and risk factors for postoperative dysphagia were evaluated by univariate analysis. Results The 5-year overall survival, disease-specific survival and larynx preservation rate of fresh hypopharyngeal cancer cases were 83.2%, 94.3% and 94.6%, respectively. Those of supraglottic cancer cases were 80%, 95% and 94.7%, respectively. Those of salvage cases were 87.5%, 87.5% and 82.5%, respectively. Those of T3 and T4 hypopharyngeal cancer treated by neoadjuvant chemotherapy with TOVS were 75.0%, 82.5% and 100% respectively. Surgical complication included bleeding (2.6%) and emergency tracheostomy (3.4%). Oral intake was maintained in 94.8% cases. By univariate analysis, patient’s age (especially 80 years of age or older), larger resected area, arytenoid resection and tracheostomy were regarded as risk factors for postoperative dysphagia. Among 31 recent cases, 5 cases had difficulty in exposing hypopharyngeal lesions by conventional blades. These exposure problems were solved by curved blades. Conclusion Using malleable devices and new curved blades for the FKWO retractor, exposure problems in the hypopharynx could be solved and TOVS could be applied in more cases. Although oncological outcomes and functional outcomes were good, patients with risk factors for dysphagia should be carefully indicated.

Redox chemistry of d6 iron(II) and ruthenium(II) complexes has been studied extensively due to the interesting reactivity of mononuclear radical species and the charge-delocalized properties of dinuclear mixed-valence (MV) complexes. In particular, organometallic dinuclear MV systems show long-range charge-delocalized behavior, and their properties can be modified by the choice of the metal (M) and the bridging ligand (BL). Here we review mono- and di-nuclear radical species having CP2M and CPM(dppe) fragments (CP = η5-C5H5 or η5-C5Me5; M = Fe, Ru) as the redox centers. Although the Fe and Ru species are frequently isostructural, the electronic structures of them are considerably different. Radical center tends to localize rather on the metal center and the ligand part in the Fe and Ru complexes, respectively. For mononuclear species, the Ru complexes exhibit reactivity at the ligand to undergo radical coupling, whereas the Fe complexes may stay as monomeric radical species. For dinuclear complexes, the radical center of mixed-valence diiron species rather localizes on the metal center, while that of the diruthenium analogues tends to localize on the BL. The difference could be ascribed to reorganization caused by the electron transfer, and the extent of the contribution of the BL-localized state can be estimated by the difference between the νmax values for an Fe complex and its Ru derivative (Δνmax(Ru-Fe)).

Synthesis of molecular containers capable of incorporating multiple fullerenes remains challenging. Reported here is that room-temperature mixing of metal ions with W-shaped bispyridine ligands featuring polyaromatic panels results in the quantitative formation of a peanut-shaped M2 L4 capsule. The capsule reversibly converts into two molecules of an ML2 double tube in response to changes in the solvent. Notably, the capsule allows the incorporation of two fullerene molecules into the connected two spherical cavities at room temperature. The close proximity yet non-contact of the encapsulated C60 molecules, with a separation of 6.4 A, was revealed by X-ray crystallographic analysis. The resultant, unusual fullerene dimer undergoes sequential reduction within the capsule to generate (C60.- )2 , C60.- ⋅C602- , and (C602- )2 species. Furthermore, temperature-controlled stepwise incorporation of two C60 molecules into the capsule is demonstrated.

We propose an automatic detection method for early stage gastric cancer from endoscopic images that uses the fast discrete curvelet transform (FDCT) and wavelet transform modulus maxima (WTMM). First, we convert an original image to CIE L*a*b* color space and apply the dyadic wavelet transform (DYWT) to the a* component of the image. Next, we compute the WTMM using the high frequency components obtained by the DYWT and generate a binary image based on the WTMM. We then produce a composite image using the L* and a* components of the image and compute the curvelet coefficient by applying FDCT to the composite image. In addition, we apply the inverse curvelet transform to only the imaginary component of the curvelet coefficient and generate a binarized image by applying threshold processing to the obtained image. We divide the two binarized images into non-overlapped blocks and compute the average value of each block. The average value of the block corresponding to the abnormal portion tends to be smaller than that of the entire image. On the basis of these features, we describe in detail a method of detecting abnormal regions and show by our experimental results that the proposed method can detect the region in the endoscopic image that may indicate early stage gastric cancer.

The cell wall integrity and stress response component (WSC) domain was first described in the Wsc-family protein of the yeast Saccharomyces cerevisiae, and later found in diverse eukaryotic organisms. Due solely to their presence in the Wsc-family proteins working as a plasma membrane sensor for surface stress and in a fungal β-1,3-exoglucanse, WSC domains have been presumed to possess carbohydrate-binding property without any experimental evidence. Aiming at elucidation of function(s) of WSC domains, we characterized a WSC domain-containing alcohol oxidase from the rice blast pathogen Pyricularia oryzae (PoAlcOX). Recombinant PoAlcOX produced with Pichia pastoris showed alcohol oxidase activity toward a wide range of substrates including two aliphatic alcohols, a branched-chain alcohol, a diol, and a polyol. Deletion of the WSC domain virtually unaffected oxidation of these substrates by PoAlcOX, indicating that the domain makes no contribution to the catalytic activity. In analogy to some carbohydrate-binding modules, we inferred that the WSC domain plays a role in protein anchoring, and evaluated binding capability of PoAlcOX to a set of polysaccharide components of fungal and plant cell walls. This revealed that PoAlcOX binds to xylans and fungal chitin/β-1,3-glucan in the WSC domain-dependent manner, demonstrating for the first time the carbohydrate-binding property of the domain. Additionally, we provide evidence that PoAlcOX immobilized on birch wood xylan retains the catalytic activity. Overall, the data we collected suggest that the role of the WSC domain of PoAlcOX is not recognition of substrates but attaching the enzyme to plant and/or fungal cell wall.

In clinical N0 (cN0) cases with head and neck squamous cell carcinoma (HNSCC), a treatment selection is still controversial: elective neck dissection or watchful waiting. We focused on sentinel lymph node (SLN)–targeted therapy using the urokinase-type plasminogen activator (uPA)-dependent oncolytic Sendai virus “BioKnife.” The objectives of this study were to investigate BioKnife migration into SLNs and elucidate its antitumor effect on lymph node metastases (LNM). We established an orthotopic nude mouse model of HNSCC, with LNM being frequently induced. We inoculated HSC-3-M3, human highly metastatic tongue squamous cell carcinoma cells, in the tongue of the nude mice, and after 2 weeks, we injected BioKnife into the primary tumor. We tracked BioKnife migration into the SLNs by immunostaining, RT-PCR, and an in vivo imaging system. We also examined its antitumor effects and mechanisms through serial section analysis of lymph nodes. GFP reporter expression was clearly visible in the lymph nodes of virus groups, which corresponded to SLNs. Relative GFP mRNA was significantly increased in both the tongues and lymph nodes in the virus groups compared with that in the control group (P < 0.05). Serial section analysis showed that BioKnife infected cancer cells and exhibited significant antitumor effect against LNM compared with the control groups (P < 0.05). We detected apoptosis in LNM infected by BioKnife. BioKnife migrated into SLNs after its injection into the primary tumor and effectively suppressed LNM, suggesting that SLN-targeted therapy using BioKnife has great potential to provide a novel and promising alternative to elective neck dissection in cN0 patients with HNSCC.

Many neuropsychiatric risk genes contribute to epigenetic regulation of gene expression but very little is known about specific chromatin-associated mechanisms governing the formation and maintenance of neuronal connectivity. Here we show that transcallosal connectivity is critically dependent on C11orf46 (also known as ARL14EP), a small nuclear protein encoded in the chromosome 11p13 Wilms Tumor, Aniridia, Genitourinary Abnormalities, intellectual disability (formerly referred to as Mental Retardation) (WAGR) risk locus. C11orf46 haploinsufficiency in WAGR microdeletion cases was associated with severe hypoplasia of the corpus callosum. In utero short hairpin RNA-mediated C11orf46 knockdown disrupted transcallosal projections of cortical pyramidal neurons, a phenotype that was rescued by wild type C11orf46 but not the C11orf46R236H mutant associated with autosomal recessive intellectual disability. Multiple genes encoding key regulators of axonal growth and differentiation, including Sema6A, were hyperexpressed in C11orf46-knockdown neurons. Importantly, RNA-guided epigenetic editing of neuronal Sema6a gene promoters via a dCas9 protein-conjugated SunTag scaffold with multimeric (10x) C11orf46 binding during early developmental periods, resulted in normalization of expression and rescue of transcallosal dysconnectivity via repressive chromatin remodeling, including up-regulated histone H3K9 methylation by the KAP1-SETDB1 repressor complex. Our study demonstrates that interhemispheric communication is highly sensitive to locus-specific remodeling of neuronal chromatin, revealing the therapeutic potential for shaping the brain’s connectome via gene-targeted designer activators and repressor proteins.

Background Securing food for patients with food allergies may be more difficult during disasters, but reports on the status of household allergen-free food reserves in preparation for disasters are limited. This study investigated the household stock status of allergen-free foods in preparation for disasters in Kobe City after the Great Hanshin-Awaji Earthquake. Methods The survey targets were 172 parents of patients with a food allergy who underwent in-hospital oral food challenge test for allergies at four hospitals from October 2016 to March 2017. Of these, 158 patients with allergies to eggs, milk and wheat were included in the analysis. The first survey was performed to investigate patient characteristics and stockpiling status of allergen-free foods in parallel with oral food challenge tests. The second survey was performed on the follow-up visit to investigate any changes in behavior. Results Median patient age was 3 years, with boys comprising 68.4% of the patients. Eggs were the most eliminated food, and the median number of foods avoided was 2. A total of 82.3% of parents had experienced disasters. The proportion of households that stockpiled allergy-free meals was 42.4%, and the median amount was 3 days. The stockpiling situation did not differ according to the parents' disaster experience. In the second survey, 45.3% had modified their stockpiling practice. Conclusions Even in this area where the Great Hanshin-Awaji Earthquake occurred, household stockpiles of allergen-free foods are inadequate; therefore, all medical staff should educate families about the necessity of stocking allergen-free food for disasters.

Preparation of molecular nanostructures with polyradical frameworks remains a significant challenge because of the limited synthetic accessibility which is entirely different from that of neutral and ionic ones. Herein we report the quantitative formation of a new M2L4 molecular capsule from metal ions and dihydrophenazine-based ligands. The capsule has a spherical nanocavity (ca. 1 nm in diameter) enclosed by eight redox-active, dihydrophenazine panels. Electrochemical oxidation of the capsule leads to the generation of multiple radical cations on the shell framework. Moreover, a stable tetra(radical cation) capsule can be reversibly obtained by chemical as well as electrochemical oxidation.