Extremely stable system of 1-haloselanyl-anthraquinones: experimental and theoretical investigations.

Highly stable selanyl halides, 1-ATQSeX (X = I (1), Br (2) and Cl (3)), were prepared. The structures of 1, 2, 6 (1-ATQSeX: X = Me) and 7 (1-ATQBr) were determined. QC calculations were performed on 1-3, 4 (X = F), 5 (X = H), 6, 7 and 8 (X = SeATQ-1). The O⋯Se distances in 1-4 from the sum of the vdW radii of the atoms (Δr(Se, O1)) were less than -1 Å, in magnitude, which must be the driving force for the high stability. The O-*-Se interactions seem stronger in the order of 1 < 2 < 3 < 4. The intrinsic dynamic and static natures of O⋯Se and/or Se⋯X in 1-8 are elucidated by QTAIM dual functional analysis (QTAIM-DFA). The Se-*-I, Se-*-Br, Se-*-Cl and Se-*-F interactions in 1-4 are predicted to have the natures of covalent, TBP with CT, TBP with CT, and typical HB with covalency, respectively, whereas O-*-Ses in 1-4 are all predicted to have the nature of MC with CT. The Se-*-H, Se-*-CMe and Se-*-Se interactions in 5, 6 and 8 are all predicted to have the covalent nature, while O-*-Ses in 5, 6 and 8 are all predicted to have the nature of typical HB with no covalency. The E(2) values of 1-6 and 8 are calculated with NBO analysis, and correlate excellently with Δr(Se, O1), except for Se-*-F, for which E(2) is evaluated to be much larger. The E(2) values also correlate very well with Cii-1 for all Se-*-X in 1-4, although data from 5, 6 and 8 deviated from the correlation, where Cii is the diagonal element of the compliance (force) constant for the internal vibrations. The behaviour of the interactions is further examined based on the QTAIM-DFA parameters of θ and θp. The stabilizing effect is further confirmed by the calculations with the ν(CO) values analyzed carefully.

Chromic properties of dibenzo[j,l]fluoranthenes exhibiting different resonance contributions.

Chromic molecules change colour in response to external stimuli and are utilized in applications such as food additive detection, light dimmers, and biological probes. One of the common design strategies for organic chromic molecules is based on changes in the π-conjugation. We have hypothesized that non-alternant polyaromatic hydrocarbon (PAH) skeletons can be used as backbones for chromic molecules. Herein, we synthesized hydroxy-substituted dibenzo[j,l]fluoranthenes, a class of non-alternant PAHs, as novel chromic compounds and evaluated their halochromic properties by UV-vis and fluorescence spectroscopy. Under basic conditions, the 1-hydroxy derivatives show a hyperchromic shift, whereas the 9-hydroxy derivatives show a bathochromic shift and fluorescence although the skeleton of the chromophore is the same. Density functional theory calculations indicated that the different chromic properties are attributed to the differences in their resonance structures.

Morphology of the pterothoracic musculature in Paraneoptera and its phylogenetic implication (Insecta: Neoptera).

Although the monophyly of Paraneoptera (=hemipteroid orders or Acercaria, composed of Psocodea, Thysanoptera and Hemiptera) has been widely accepted morphologically, the results from molecular phylogenetic and phylogenomic analyses contradict this hypothesis. In particular, phylogenomic analyses provide strong bootstrap support for the sister group relationship between Psocodea and Holometabola, that is, paraphyly of Paraneoptera. Here, we examined the pterothoracic musculature of Paraneoptera, as well as a wide range of other neopterous insect orders, and analysed its phylogenetic implication. By using the synchrotron microcomputed tomography (µCT) and parsimony-based ancestral state reconstruction, several apomorphic conditions suggesting the monophyly of Paraneoptera, such as the absence of the II/IIItpm7, IIscm3, IIIspm2 and IIIscm3 muscles, were identified. In contrast, no characters supporting Psocodea + Holometabola were recovered from the thoracic muscles. These results provide additional support for the monophyly of Paraneoptera, together with the previously detected morphological apomorphies of the head, wing base, and abdomen.

Giant Modulation of the Second Harmonic Generation by Magnetoelectricity in Two-Dimensional Multiferroic CuCrP2S6.

Multiferroic materials have attracted considerable attention owing to their unique magnetoelectric or magnetooptical properties. The recent discovery of few-layer van der Waals multiferroic crystals provides a new research direction for controlling the multiferroic properties in the atomic layer limit. However, research on few-layer multiferroic crystals is limited and the effect of thickness-dependent symmetries on those properties is less explored. In this study, the symmetries and magnetoelectric responses of van der Waals multiferroic CuCrP2S6 are investigated by optical second harmonic generation (SHG). Structural and magnetic phase transitions are successfully probed by the temperature-dependent SHG signals, revealing significant changes by applying the magnetic field reflecting the magnetoelectric effect. Moreover, it is found that symmetries and resultant magnetoelectric responses can be modulated by the number of layers. These results offer a new principle of controlling the multiferroicity and indicate that 2D van der Waals multiferroic material is a promising building block for functional nanodevices.

Optimization Efforts for Identification of Novel Highly Potent Keap1-Nrf2 Protein-Protein Interaction Inhibitors.

In research focused on protein-protein interaction (PPI) inhibitors, the optimization process to achieve both high inhibitory activity and favorable physicochemical properties remains challenging. Our previous study reported the discovery of novel and bioavailable Keap1-Nrf2 PPI inhibitor 8 which exhibited moderate in vivo activity in rats. In this work, we present our subsequent efforts to optimize this compound. Two distinct approaches were employed, targeting high energy water molecules and Ser602 as "hot spots" from the anchor with good aqueous solubility, metabolic stability, and membrane permeability. Through ligand efficiency (LE)-guided exploration, we identified two novel inhibitors 22 and 33 with good pharmacokinetics (PK) profiles and more potent in vivo activities, which appear to be promising chemical probes among the existing inhibitors.

Silicone-based highly stretchable multifunctional fiber pumps.

Recent advancements on electrohydrodynamic (EHD) soft pumps demonstrate their applicability to various fluid-driven systems such as soft robots, wearable devices, and stretchable electronics. In particular, fiber type EHD pumps reported more recently is a promising pumping element thanks to their versatile fibrous structure. Yet existing EHD fiber pumps are less stretchable and require sophisticated, complex fabrication equipment, implying opportunity for technology advancement. This paper presents a simplified method to create highly stretchable multifunctional fiber EHD pumps. The method employs highly compliant silicone elastomers for the fiber structure that is formed by simple dipping fabrication process. The fabricated pumps (length of 100 mm, inner diameter 4 mm, and mass 5.3 g) exhibit a high stretchability (up to 40% strain) and flow rate and pressure of 167.4 ± 7.6 mL/min (31.6 mL/min/g) and 4.1 ± 0.6 kPa (0.8 kPa/g), respectively. These performances are comparable or even higher than those of previously reported EHD pumps including fiber types. The output performance of the fabricated pumps remain constant for repeated strain cycles (0-25%, up to 2000 cycles) and bending angle up to 180° (corresponding to curvature of 0-30/m). Moreover, the pumps demonstrate unprecedented functionality as a sensor to distinguish the type of fluid inside the tube and to detect strains by reading the capacitance between the electrodes. The characterization result reveals the sensing ability of the pumps as high repeatability up to 30% strain with negligible hysteresis, which is consistent for 5000 cycles.

Emergent zero-field anomalous Hall effect in a reconstructed rutile antiferromagnetic metal.

The anomalous Hall effect (AHE) that emerges in antiferromagnetic metals shows intriguing physics and offers numerous potential applications. Magnets with a rutile crystal structure have recently received attention as a possible platform for a collinear-antiferromagnetism-induced AHE. RuO2 is a prototypical candidate material, however the AHE is prohibited at zero field by symmetry because of the high-symmetry [001] direction of the Néel vector at the ground state. Here, we show AHE at zero field in Cr-doped rutile, Ru0.8Cr0.2O2. The magnetization, transport and density functional theory calculations indicate that appropriate doping of Cr at Ru sites reconstructs the collinear antiferromagnetism in RuO2, resulting in a rotation of the Néel vector from [001] to [110] while maintaining a collinear antiferromagnetic state. The AHE with vanishing net moment in the Ru0.8Cr0.2O2 exhibits an orientation dependence consistent with the [110]-oriented Hall vector. These results demonstrate that material engineering by doping is a useful approach to manipulate AHE in antiferromagnetic metals.

Conformational Selectivity of ITK Inhibitors: Insights from Molecular Dynamics Simulations.

Interleukin-2-inducible T-cell kinase (ITK) regulates the response to T-cell receptor signaling and is a drug target for inflammatory and immunological diseases. Molecules that bind preferentially to the active form of ITK have low selectivity between kinases, whereas those that bind preferentially to the inactive form have high selectivity for ITK. Therefore, computational methods to predict the conformational selectivity of compounds are required to design highly selective ITK inhibitors. In this study, we performed absolute binding free-energy perturbation (ABFEP) simulations for 11 compounds on both active and inactive forms of ITK, and the calculated binding free energies were compared with experimental data. The conformational selectivity of 10 of the 11 compounds was correctly predicted using ABFEP. To investigate the mechanism underlying the stabilization of the active and inactive structures by the compounds, we performed extensive, conventional molecular dynamics simulations, which revealed that the compound-induced stabilization of the P-loop and linkage of conformational changes in L489, V419, F501, and M410 upon compound binding were critical factors. A guideline for designing inactive-form binders is proposed based on these key structural factors. The ABFEP and the created guidelines are expected to facilitate the discovery of highly selective ITK inhibitors.

Artificially controlled nanoscale chemical reduction in VO2 through electron beam illumination.

Chemical reduction in oxides plays a crucial role in engineering the material properties through structural transformation and electron filling. Controlling the reduction at nanoscale forms a promising pathway to harvest functionalities, which however is of great challenge for conventional methods (e.g., thermal treatment and chemical reaction). Here, we demonstrate a convenient pathway to achieve nanoscale chemical reduction for vanadium dioxide through the electron-beam illumination. The electron beam induces both surface oxygen desorption through radiolytic process and positively charged background through secondary electrons, which contribute cooperatively to facilitate the vacancy migration from the surface toward the sample bulk. Consequently, the VO2 transforms into a reduced V2O3 phase, which is associated with a distinct insulator to metal transition at room temperature. Furthermore, this process shows an interesting facet-dependence with the pronounced transformation observed for the c-facet VO2 as compared with the a-facet, which is attributed to the intrinsically different oxygen vacancy formation energy between these facets. Remarkably, we readily achieve a lateral resolution of tens nanometer for the controlled structural transformation with a commercial scanning electron microscope. This work provides a feasible strategy to manipulate the nanoscale chemical reduction in complex oxides for exploiting functionalities.

Methyl and Fluorine Effects in Novel Orally Bioavailable Keap1-Nrf2 PPI Inhibitor.

Oxidative stress is one of the causes of progression of chronic kidney disease (CKD). Activation of the antioxidant protein regulator Nrf2 by inhibition of the Keap1-Nrf2 protein-protein interaction (PPI) is of interest as a potential treatment for CKD. We report the identification of the novel and weak PPI inhibitor 7 with good physical properties by a high throughput screening (HTS) campaign, followed by structural and computational analysis. The installation of only methyl and fluorine groups successfully provided the lead compound 25, which showed more than 400-fold stronger activity. Furthermore, these dramatic substituent effects can be explained by the analysis of using isothermal titration calorimetry (ITC). Thus, the resulting 25, which exhibited high oral absorption and durability, would be a CKD therapeutic agent because of the dose-dependent manner for up-regulation of the antioxidant protein heme oxigenase-1 (HO-1) in rat kidneys.

Polyvinyl chloride-added dibutyl adipate for high-performance electrohydrodynamic pumps.

Electrohydrodynamic (EHD) pumps are a promising driving source for various fluid-driven systems owing to features such as simple structure and silent operation. The performance of EHD pumps depends on the properties of the working fluid, such as conductivity, viscosity, and permittivity. This implies that the tuning of these parameters in a working fluid can enhance the EHD performance. This study reports a method to modify the properties of a liquid for EHD pumps by mixing an additive. Specifically, dibutyl adipate (DBA) and polyvinyl chloride (PVC) are employed as the working fluid and the additive, respectively. The results show that when the concentration of PVC is 0.2%, the flow rate and pressure at applied voltage of 8 kV take highest value of 7.85 µL/s and 1.63 kPa, respectively. These values correspond to an improvement of 109% and 40% for the flow rate and pressure, respectively, compared to the pure DBA (PVC 0%). When the voltage is 10 kV, the flow rate of 10.95 µL/s and the pressure of 2.07 kPa are observed for DBA with PVC concentration of 0.2%. These values are more than five times higher than those observed for FC40 at the same voltage (2.02 µL/s and 0.32 kPa). The results also suggest that optimal conductivity and viscosity values exist for maximizing the EHD performance of a liquid. This demonstrates the validity of the proposed method for realizing high-performance EHD pumps by using additives in the working fluid.

Estimation of Degradation Degree in Road Infrastructure Based on Multi-Modal ABN Using Contrastive Learning.

This study presents a method for distress image classification in road infrastructures introducing self-supervised learning. Self-supervised learning is an unsupervised learning method that does not require class labels. This learning method can reduce annotation efforts and allow the application of machine learning to a large number of unlabeled images. We propose a novel distress image classification method using contrastive learning, which is a type of self-supervised learning. Contrastive learning provides image domain-specific representation, constraining such that similar images are embedded nearby in the latent space. We augment the single input distress image into multiple images by image transformations and construct the latent space, in which the augmented images are embedded close to each other. This provides a domain-specific representation of the damage in road infrastructure using a large number of unlabeled distress images. Finally, the representation obtained by contrastive learning is used to improve the distress image classification performance. The obtained contrastive learning model parameters are used for the distress image classification model. We realize the successful distress image representation by utilizing unlabeled distress images, which have been difficult to use in the past. In the experiments, we use the distress images obtained from the real world to verify the effectiveness of the proposed method for various distress types and confirm the performance improvement.

Real-Space Observation of Ripple-Induced Symmetry Crossover in Ultrathin MnPS3.

Stacking order is expected to have a significant impact on the properties of van der Waals layered magnets, as it determines the crystallographic and magnetic symmetry. Recent synchrotron-based optical studies on antiferromagnetic MnPS3 have revealed a thickness-dependent symmetry crossover, suggesting possible different stackings in few-layer crystals from the bulk, which, however, has not been explicitly identified. Here, by using a combination of atomic-scale electron microscopy and theoretical calculations, we show that despite the bulk monoclinic stacking persists macroscopically down to bilayer, additional local rippling effect lifts the monoclinic symmetry of the few layers while preserving the trigonal symmetry of individual monolayers, leading to possible monolayer-like behavior in ultrathin MnPS3 samples. This finding reveals the profound impact of rippling on the microscopic symmetry of two-dimensional materials with weak interlayer interactions and raises the possibility of approaching the paradigmatic two-dimensional Néel antiferromagnetic honeycomb lattice in MnPS3 without reaching monolayer thickness.

Giant bulk piezophotovoltaic effect in 3R-MoS2.

Given its innate coupling with wavefunction geometry in solids and its potential to boost the solar energy conversion efficiency, the bulk photovoltaic effect (BPVE) has been of considerable interest in the past decade1-14. Initially discovered and developed in ferroelectric oxide materials2, the BPVE has now been explored in a wide range of emerging materials, such as Weyl semimetals9,10, van der Waals nanomaterials11,12,14, oxide superlattices15, halide perovskites16, organics17, bulk Rashba semiconductors18 and others. However, a feasible experimental approach to optimize the photovoltaic performance is lacking. Here we show that strain-induced polarization can significantly enhance the BPVE in non-centrosymmetric rhombohedral-type MoS2 multilayer flakes (that is, 3R-MoS2). This polarization-enhanced BPVE, termed the piezophotovoltaic effect, exhibits distinctive crystallographic orientation dependence, in that the enhancement mainly manifests in the armchair direction of the 3R-MoS2 lattice while remaining largely intact in the zigzag direction. Moreover, the photocurrent increases by over two orders of magnitude when an in-plane tensile strain of ~0.2% is applied, rivalling that of state-of-the-art materials. This work unravels the potential of strain engineering in boosting the photovoltaic performance, which could potentially promote the exploration of novel photoelectric processes in strained two-dimensional layered materials and their van der Waals heterostructures.

Peristaltic micropump using polyvinyl chloride gels with micropatterned surface.

This paper presents a pump using polyvinyl chloride (PVC) gel. PVC gels are compliant, have a simple structure, and exhibit large deformation at voltages in the range of 100-1000 V, which make them suitable for micropumps. In this study, a PVC gel sheet with a surface pattern that enhances active deformation in the thickness direction was employed for the fabrication of a pump. To this end, the PVC gel sheet was sandwiched between three sets of anode and cathode electrodes, after which voltages were sequentially applied to these electrodes to generate a peristaltic deformation of the gel sheet, thus pushing the liquid and creating a one-directional flow. Various pumps were fabricated using PVC gel sheets with different surface patterns, and the pumps were characterized. The pumps exhibited an outline dimension of 35 mm × 25 mm with a thickness of 4 mm, corresponding to a total volume of 3.5 × 103 mm3. The results revealed that the pump fabricated using a 174-µm-high pyramid-patterned gel sheet generated a flow rate of 224.1 µL/min at an applied voltage of 800 V and a driving frequency of 3 Hz. This observed value is comparable to or better than those of existing pumps based on smart materials.

Pattern recognition with neuromorphic computing using magnetic field-induced dynamics of skyrmions.

Nonlinear phenomena in physical systems can be used for brain-inspired computing with low energy consumption. Response from the dynamics of a topological spin structure called skyrmion is one of the candidates for such a neuromorphic computing. However, its ability has not been well explored experimentally. Here, we experimentally demonstrate neuromorphic computing using nonlinear response originating from magnetic field-induced dynamics of skyrmions. We designed a simple-structured skyrmion-based neuromorphic device and succeeded in handwritten digit recognition with the accuracy as large as 94.7% and waveform recognition. Notably, there exists a positive correlation between the recognition accuracy and the number of skyrmions in the devices. The large degrees of freedom of skyrmion systems, such as the position and the size, originate from the more complex nonlinear mapping, the larger output dimension, and, thus, high accuracy. Our results provide a guideline for developing energy-saving and high-performance skyrmion neuromorphic computing devices.

[Administration Period of Olanzapine as an Antiemetic Drug for Patients on FEC Therapy-A Survey].

Olanzapine(OLZ)is a multi-acting receptor-targeted antipsychotic drug approved in Japan in December 2017 for the treatment of anticancer drug-induced nausea and vomiting. However, the recommended doses and administration periods of OLZ in the literature and guidelines are varied. Reports on the efficacy and safety of OLZ combined with perioperative chemotherapy for breast cancer in Japanese patients are few. Moreover, the risk of nausea and vomiting during treatment with anticancer drugs in young and women patients remains to be high. In this study, we conducted an exploratory survey on the optimal duration of OLZ administration(days 1-4: 5 mg, before sleep)during perioperative breast cancer 5-fluorouracil, epirubicin, cyclophosphamide(FEC)therapy. We found that treatment with OLZ showed efficacy in improving nausea grade and maintaining relative dose intensity. Moreover, it could be used safely without interruption due to side effects, such as weight gain, elevation in blood glucose, somnolence, and insomnia. Prophylactic antiemetic therapy with OLZ administration (days 1-4: 5 mg)prior to sleep was effective in patients having FEC therapy-induced nausea and vomiting.

Morphology and phylogenetic significance of the thoracic muscles in Psocodea (Insecta: Paraneoptera).

The thoracic musculature of the insect order Psocodea has been examined in only a few species of a single suborder to date. In the present study, we examined the thoracic musculature of species selected from all three suborders of Psocodea to elucidate the ground plan of the order and to examine the phylogenetic utility of the character system. The sister-group relationship between the suborders Troctomorpha and Psocomorpha received support from two novel nonhomoplasious synapomorphies, although the support from other morphological characters for this relationship is ambiguous. The sister-group relationship between the infraorders Epipsocetae and Psocetae also received support from one nonhomoplasious synapomorphy, although no other morphological characters supporting this relationship have been identified to date. The present examination revealed the potential of thoracic muscle characters for estimating deep phylogeny, possibly including interordinal relationships.

Probiotic-derived heptelidic acid exerts antitumor effects on extraintestinal melanoma through glyceraldehyde-3-phosphate dehydrogenase activity control.

BACKGROUND: Several microorganisms inhabit the mammalian gastrointestinal tract and are associated with the pathogenesis of various diseases, including cancer. Recent studies have indicated that several probiotics produce antitumor molecules and inhibit host tumor progression. We demonstrated that heptelidic acid (HA), a sesquiterpene lactone derived from the probiotic Aspergillus oryzae, exerts antitumor effects against pancreatic cancer in vitro and in vivo. In this study, the antitumor effects of HA against extraintestinal melanoma were assessed in vitro and in vivo. RESULTS: Sulforhodamine B (SRB) assay revealed that the growth of B16F10 cells was significantly inhibited by HA in a concentration-dependent manner. The enzymatic activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) decreased in proportion with the growth inhibition effect of HA. Moreover, oral HA administration significantly suppressed the growth of transplanted B16F10 tumors without any significant changes in biochemical test values. Moreover, GAPDH activity in the transplanted tumor tissues in the HA group significantly decreased compared with that in the PBS group. CONCLUSION: This study suggests that orally administered HA was absorbed in the gastrointestinal tract, reached the cancer cells transplanted in the skin, and inhibited GAPDH activity, thereby inhibiting the growth of extraintestinal melanoma cells. Thus, this study proposes a novel system for extraintestinal tumor regulation via gut bacteria-derived bioactive mediators.

Ellagic Acid Combined with Tacrolimus Showed Synergistic Cell Growth Inhibition in Fission Yeast.

Calcineurin (CN) is a conserved Ca2+-calmodulin activated protein phosphatase, which plays important roles in immune regulation, cardiac hypertrophy, and apoptosis in humans. In pathogenic fungi, CN is essential for stress survival, sexual development, and virulence. The immunosuppressant tacrolimus (FK506) is a specific inhibitor of CN in humans and fungi including nonpathogenic fission yeast. Although calcineurin inhibition by FK506 or CN deletion in fission yeast does not induce growth defects, treatment with some anti-fungal drugs such as micafungin and valproic acid, induced synthetic lethality with calcineurin inhibition. Here, we searched for the compounds that induce synthetic growth defects with CN inhibition in fission yeast. We found that ellagic acid (EA) preferentially induced growth inhibition in CN deletion cells. Consistently, co-treatment with EA and FK506 induced severe growth inhibition in the wild-type cells, whereas neither of the single treatment with each compound did so. Moreover, deletion of the calcineurin-regulated transcription factor Prz1 also induced a marked EA sensitivity. Intriguingly, EA also enhanced the growth inhibitory effect of other anti-fungal drugs, including micafungin and miconazole. Thus, our data suggesting the synergistic growth inhibitory effect of the calcineurin inhibitor FK506 and EA may be useful to understand the mechanism to overcome the antifungal resistance.