Identification of Obscurolide-Type Metabolites and Antifungal Metabolites from the Termite-Associated Streptomyces neopeptinius BYF101.

Streptomyces spp. are well-known symbiotic microorganisms that produce antimicrobial metabolites against various pathogens. We isolated actinomycetes from the body surface of the termite Odontotermes formosanus and identified it as Streptomyces neopeptinius BYF101 based on 16S rRNA phylogenetic analysis. Chemical analysis of the cultures of termite-associated S. neopeptinius BYF101 via HR-MS2 and GNPS analyses enabled the isolation and identification of 20 metabolites, including the unreported obscurolide-type metabolites (1-3). The chemical structures of unreported compounds (1-3) were elucidated using HR-ESI-MS and 1D and 2D NMR analysis, and their absolute configurations were determined via chemical reactions followed by the application of competing enantioselective acylation (CEA) and computational methods for ECD and DP4+ probability calculation. The isolated compounds (1-20) were tested to determine their antifungal activity against two human fungal pathogens, Candida albicans and Cryptococcus neoformans. Among the compounds tested, indole-3-carboxylic acid (9) displayed antifungal activity against C. neoformans, with an MIC value of 12 µg/mL.

A wet-tolerant adhesive patch inspired by protuberances in suction cups of octopi.

Adhesion strategies that rely on mechanical interlocking or molecular attractions between surfaces can suffer when coming into contact with liquids. Thus far, artificial wet and dry adhesives have included hierarchical mushroom-shaped or porous structures that allow suction or capillarity, supramolecular structures comprising nanoparticles, and chemistry-based attractants that use various protein polyelectrolytes. However, it is challenging to develop adhesives that are simple to make and also perform well-and repeatedly-under both wet and dry conditions, while avoiding non-chemical contamination on the adhered surfaces. Here we present an artificial, biologically inspired, reversible wet/dry adhesion system that is based on the dome-like protuberances found in the suction cups of octopi. To mimic the architecture of these protuberances, we use a simple, solution-based, air-trap technique that involves fabricating a patterned structure as a polymeric master, and using it to produce a reversed architecture, without any sophisticated chemical syntheses or surface modifications. The micrometre-scale domes in our artificial adhesive enhance the suction stress. This octopus-inspired system exhibits strong, reversible, highly repeatable adhesion to silicon wafers, glass, and rough skin surfaces under various conditions (dry, moist, under water and under oil). To demonstrate a potential application, we also used our adhesive to transport a large silicon wafer in air and under water without any resulting surface contamination.

A Hierarchically Tailored Wrinkled Three-Dimensional Foam for Enhanced Elastic Supercapacitor Electrodes.

Recently, three-dimensional (3D) porous foams have been studied, but further improvement in nanoscale surface area and stretchability is required for electronic and energy applications. Herein, a general strategy is reported to form a tailored wrinkling structure on strut surfaces inside a 3D polydimethylsiloxane (PDMS) polymeric foam. Controlled wrinkles are created on the struts of 3D foam through an oxygen plasma treatment to form a bilayer surface of PDMS on uniaxially prestretched 3D PDMS foam, followed by relaxation. After plasma treatment for 1 h and prestretching of 40%, the wrinkled 3D foam greatly improves specific surface area and stretchability by over 60% and 75%, respectively, compared with the pristine 3D PDMS foam. To prove its applicability with improved performances, supercapacitors are prepared by coating a conductive material on the wrinkled 3D foam. The resulting supercapacitors exhibit an increased storage capacity (8.3 times larger), maintaining storage capacity well under stretching up to 50%.

Ulmusakidian, a new coumarin glycoside and antifungal phenolic compounds from the root bark of Ulmus davidiana var. japonica.

Bioactivity-driven LC/MS-based phytochemical analysis of the root bark extract of Ulmus davidiana var. japonica led to the isolation of 10 compounds including a new coumarin glycoside derivative, ulmusakidian (1). The structure of the new compound was elucidated using extensive spectroscopic analyses via 1D and 2D NMR spectroscopic data interpretations, HR-ESIMS, and chemical transformation. The isolated compounds 1-10 were tested for their antifungal activity against human fungal pathogens Cryptococcus neoformans and Candida albicans. Compounds 9 and 10 showed antifungal activity against C. neoformans, with the lowest minimal inhibitory concentration (MIC) of 12.5-25.0 µg/mL, whereas none of the compounds showed antifungal activity against C. albicans.

Estrogenic Activity of Mycoestrogen (3ß,5α,22E)-Ergost-22-en-3-ol via Estrogen Receptor α-Dependent Signaling Pathways in MCF-7 Cells.

Armillariella tabescens (Scop.) Sing., a mushroom of the family Tricholomataceae, has been used in traditional oriental medicine to treat cholecystitis, improve bile secretion, and regulate bile-duct pressure. The present study evaluated the estrogen-like effects of A. tabescens using a cell-proliferation assay in an estrogen-receptor-positive breast cancer cell line (MCF-7). We found that the methanol extract of A. tabescens fruiting bodies promoted cell proliferation in MCF-7 cells. Using bioassay-guided fractionation of the methanol extract and chemical investigation, we isolated and identified four steroids and four fatty acids from the active fraction. All eight compounds were evaluated by E-screen assay for their estrogen-like effects in MCF-7 cells. Among the tested isolates, only (3ß,5α,22E)-ergost-22-en-3-ol promoted cell proliferation in MCF-7 cells; this effect was mitigated by the ER antagonist, ICI 182,780. The mechanism underlying the estrogen-like effect of (3ß,5α,22E)-ergost-22-en-3-ol was evaluated using Western blot analysis to detect the expression of extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), Akt, and estrogen receptor α (ERα). We found that (3ß,5α,22E)-ergost-22-en-3-ol induced an increase in phosphorylation of ERK, PI3K, Akt, and ERα. Together, these experimental results suggest that (3ß,5α,22E)-ergost-22-en-3-ol is responsible for the estrogen-like effects of A. tabescens and may potentially aid control of estrogenic activity in menopause.

Hydrophobicity Evolution on Rough Surfaces.

Hydrophobicity is abundant in nature and obtainable in industrial applications by roughening hydrophobic surfaces and engineering micropatterns. Classical wetting theory explains how surface roughness can enhance water repellency, assuming a droplet to have a flat bottom on top of micropatterned surfaces. However, in reality, a droplet can partially penetrate into micropatterns to form a round-bottom shape. Here, we systematically investigate the evolution of evaporating droplets on micropatterned surfaces with X-ray microscopy combined with three-dimensional finite element analyses and propose a theory that explains the wetting transition with gradually increasing penetration depth. We show that the penetrated state with a round bottom is inevitable for a droplet smaller than the micropattern-dependent critical size. Our finding reveals a more complete picture of hydrophobicity involving the partially penetrated state and its role in the wetting state transition and can be applied to understand the stability of water repellency of rough hydrophobic surfaces.

Ginkgobilol, a new diarylpentanoid and an osteogenic diarylpentanoid analog from Ginkgo biloba leaves.

Phytochemical analysis of methanol extracts of Ginkgo biloba leaves resulted in the isolation of a novel diarylpentanoid, ginkgobilol (1) and a known diarylpentanoid analog (2). The structure of the new compound was elucidated by analyzing NMR spectroscopic data and HR-ESIMS, and the absolute configuration was determined using gauge-including atomic orbital NMR chemical shift calculations, followed by DP4+ analysis and specific rotation value. Diarylpentanoids comprise two aromatic rings linked by a five-carbon bridge; these are relatively unique examples in natural products. To the best of our knowledge, the present study is the first to report the presence of diarylpentanoids in G. biloba. Compound 2 increased alkaline phosphatase (ALP) production in C3H10T1/2, a murine mesenchymal stem cell line, in a dose-dependent manner. The promotion of osteogenic differentiation by the active compound 2 mediated by induction of transcriptional ALP and osteopontin (OPN) gene expression was confirmed using quantitative real time polymerase chain reaction, thus indicating its remarkable bone formation activity.

Antifungal Phenols from Woodfordia uniflora Collected in Oman.

Woodfordia uniflora is a flowering shrub unique to the Dhofar region of Oman and is used locally as a sedative and remedy for skin infection. However, no study to date has examined the pharmacological properties of this plant, and studies regarding phytochemicals present in W. uniflora are limited. Herein, phytochemical screening of the extract of W. uniflora was performed using LC/MS. Three new phenolic compounds, (±)-woodfordiamycin (1), woodfordic acid (2), and rhamnetin 3-O-(6″-galloyl)-ß-d-glucopyranoside (3), together with 16 known compounds 4-19, were isolated from the antifungal fraction of the extract. The structures of the new compounds were established by NMR and HR-MS data, and their absolute configurations were established using chemical transformations, including Mosher's method, comparison of experimental and calculated electronic circular dichroism data, and gauge-including atomic orbital NMR chemical shift calculations, followed by DP4+ analysis. The isolated compounds (1-19) were tested for antifungal activity against human fungal pathogens Cryptococcus neoformans and Candida albicans. Compounds (±)-1 and 8 showed antifungal activity against C. neoformans, with the lowest minimum inhibitory concentrations of 1.8-1.9 µM, which was ∼10-fold lower than that of the currently available antifungal drug fluconazole, while (±)-1, 8, and 19 showed antifungal activity against C. albicans.

Self-Powered Pressure- and Vibration-Sensitive Tactile Sensors for Learning Technique-Based Neural Finger Skin.

Finger skin electronics are essential for realizing humanoid soft robots and/or medical applications that are very similar to human appendages. A selective sensitivity to pressure and vibration that are indispensable for tactile sensing is highly desirable for mimicking sensory mechanoreceptors in skin. Additionally, for a human-machine interaction, output signals of a skin sensor should be highly correlated to human neural spike signals. As a demonstration of fully mimicking the skin of a human finger, we propose a self-powered flexible neural tactile sensor (NTS) that mimics all the functions of human finger skin and that is selectively and sensitively activated by either pressure or vibration stimuli with laminated independent sensor elements. A sensor array of ultrahigh-density pressure (20 × 20 pixels on 4 cm2) of interlocked percolative graphene films is fabricated to detect pressure and its distribution by mimicking slow adaptive (SA) mechanoreceptors in human skin. A triboelectric nanogenerator (TENG) was laminated on the sensor array to detect high-frequency vibrations like fast adaptive (FA) mechanoreceptors, as well as produce electric power by itself. Importantly, each output signal for the SA- and FA-mimicking sensors was very similar to real neural spike signals produced by SA and FA mechanoreceptors in human skin, thus making it easy to convert the sensor signals into neural signals that can be perceived by humans. By introducing microline patterns on the top surface of the NTS to mimic structural and functional properties of a human fingerprint, the integrated NTS device was capable of classifying 12 fabrics possessing complex patterns with 99.1% classification accuracy.

Hepatoprotective Potency of Chrysophanol 8-O-Glucoside from Rheum palmatum L. against Hepatic Fibrosis via Regulation of the STAT3 Signaling Pathway.

Rhubarb is a well-known herb worldwide and includes approximately 60 species of the Rheum genus. One of the representative plants is Rheum palmatum, which is prescribed as official rhubarb due to its pharmacological potential in the Korean and Chinese pharmacopoeia. In our bioactive screening, we found out that the EtOH extract of R. palmatum inhibited hepatic stellate cell (HSC) activation by transforming growth factor ß1 (TGF-ß1). Chemical investigation of the EtOH extract led to the isolation of chrysophanol 8-O-glucoside, which was determined by structural analysis using NMR spectroscopic techniques and electrospray ionization mass spectrometry (ESIMS). To elucidate the effects of chrysophanol 8-O-glucoside on HSC activation, activated LX-2 cells were treated for 48 h with chrysophanol 8-O-glucoside, and α-SMA and collagen, HSC activation markers, were measured by comparative quantitative real-time PCR (qPCR) and western blotting analysis. Chrysophanol 8-O-glucoside significantly inhibited the protein and mRNA expression of α-SMA and collagen compared with that in TGF-ß1-treated LX-2 cells. Next, the expression of phosphorylated SMAD2 (p-SMAD2) and p-STAT3 was measured and the translocation of p-STAT3 to the nucleus was analyzed by western blotting analysis. The expression of p-SMAD2 and p-STAT3 showed that chrysophanol 8-O-glucoside strongly downregulated STAT3 phosphorylation by inhibiting the nuclear translocation of p-STAT3, which is an important mechanism in HSC activation. Moreover, chrysophanol 8-O-glucoside suppressed the expression of p-p38, not that of p-JNK or p-Erk, which can activate STAT3 phosphorylation and inhibit MMP2 expression, the downstream target of STAT3 signaling. These findings provided experimental evidence concerning the hepatoprotective effects of chrysophanol 8-O-glucoside against liver damage and revealed the molecular basis underlying its anti-fibrotic effects through the blocking of HSC activation.

Identification of Anti-Inflammatory Compounds from Hawaiian Noni (Morinda citrifolia L.) Fruit Juice.

Noni (Morinda citrifolia L.) fruit juice has been used in Polynesia as a traditional folk medicine and is very popular worldwide as a functional food supplement. In this study, compounds present in Hawaiian Noni fruit juice, with anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were identified. Five compounds were isolated using a bioassay-driven technique and phytochemical analysis of noni fruit juice: asperulosidic acid (1), rutin (2), nonioside A (3), (2E,4E,7Z)-deca-2,4,7-trienoate-2-O-ß-d-glucopyranosyl-ß-d-glucopyranoside (4), and tricetin (5). The structures of these five compounds were determined via NMR spectroscopy and LC/MS. In an anti-inflammatory assay, compounds 1-5 inhibited the production of nitric oxide (NO), which is a proinflammatory mediator, in LPS-stimulated macrophages. Moreover, the mechanisms underlying the anti-inflammatory effects of compounds 1-5 were investigated. Parallel to the inhibition of NO production, treatment with compounds 1-5 downregulated the expression of IKKα/ß, I-κBα, and NF-κB p65 in LPS-stimulated macrophages. Furthermore, treatment with compounds 1-5 downregulated the expression of nitric oxide synthase and cyclooxygenase-2. Thus, these data demonstrated that compounds 1-5 present in noni fruit juice, exhibited potential anti-inflammatory activity; these active compounds may contribute preventively and therapeutically against inflammatory diseases.

A transparent, glue-free, skin-attachable graphene pressure sensor with micropillars for skin-elasticity measurement.

Strong peeling resistance and water-drainable properties on rough and wet skin surfaces are highly desirable for realizing wearable and skin-attachable electronic sensors. Here, we propose a transparent, sensitive, glue-free pressure sensor for skin electronics. To achieve a thin, light-weight, transparent, and stretchable sensor patch, we laminated a single-layer graphene film as a sensing element on a thin polymeric supporter of polydimethylsiloxane. By assembling the graphene layer with densely populated micropillars, the pressure sensor achieved 10 times the sensitivity of a similar sensor without micropillars in the low-pressure range (<6 kPa). We then employed hexagonal patterns inspired by the toe pads of a tree frog, giving the assembled patch sensor with strong peeling resistance under both dry and wet conditions on surfaces such as silicon (15.5 J cm-2 for dry and 11.6 J cm-2 for wet conditions) and pig skin (2.0 J cm-2 for dry and 1.4 J cm-2 for wet conditions) without contamination after detachment. Our layered sensor patch also demonstrated successful measurement of water-dependent skin elasticity with transparent, conformal, and residual-free attachment, suggesting a variety of cosmetic and medical applications.

Suppression of 6-Hydroxydopamine-Induced Oxidative Stress by Hyperoside Via Activation of Nrf2/HO-1 Signaling in Dopaminergic Neurons.

In our ongoing research to discover natural products with neuroprotective effects, hyperoside (quercetin 3-O-galactoside) was isolated from Acer tegmentosum, which has been used in Korean traditional medicine to treat liver-related disorders. Here, we demonstrated that hyperoside protects cultured dopaminergic neurons from death via reactive oxygen species (ROS)-dependent mechanisms, although other relevant mechanisms of hyperoside activity remain largely uncharacterized. For the first time, we investigated the neuroprotective effects of hyperoside on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in neurons, and the possible underlying mechanisms. Hyperoside significantly ameliorated the loss of neuronal cell viability, lactate dehydrogenase release, excessive ROS accumulation and mitochondrial membrane potential dysfunction associated with 6-OHDA-induced neurotoxicity. Furthermore, hyperoside treatment activated the nuclear erythroid 2-related factor 2 (Nrf2), an upstream molecule of heme oxygenase-1 (HO-1). Hyperoside also induced the expression of HO-1, an antioxidant response gene. Remarkably, we found that the neuroprotective effects of hyperoside were weakened by an Nrf2 small interfering RNA, which blocked the ability of hyperoside to inhibit neuronal death, indicating the vital role of HO-1. Overall, we show that hyperoside, via the induction of Nrf2-dependent HO-1 activation, suppresses neuronal death caused by 6-OHDA-induced oxidative stress. Moreover, Nrf2-dependent HO-1 signaling activation represents a potential preventive and therapeutic target in Parkinson's disease management.

Hybrid Architectures of Heterogeneous Carbon Nanotube Composite Microstructures Enable Multiaxial Strain Perception with High Sensitivity and Ultrabroad Sensing Range.

Low-dimensional nanomaterials are widely adopted as active sensing elements for electronic skins. When the nanomaterials are integrated with microscale architectures, the performance of the electronic skin is significantly altered. Here, it is shown that a high-performance flexible and stretchable electronic skin can be produced by incorporating a piezoresistive carbon nanotube composite into a hierarchical topography of micropillar-wrinkle hybrid architectures that mimic wrinkles and folds in human skin. Owing to the unique hierarchical topography of the hybrid architectures, the hybrid electronic skin exhibits versatile and superior sensing performance, which includes multiaxial force detection (normal, bending, and tensile stresses), remarkable sensitivity (20.9 kPa-1 , 17.7 mm-1 , and gauge factor of 707 each for normal, bending, and tensile stresses), ultrabroad sensing range (normal stress = 0-270 kPa, bending radius of curvature = 1-6.5 mm, and tensile strain = 0-50%), sensing tunability, fast response time (24 ms), and high durability (>10 000 cycles). Measurements of spatial distributions of diverse mechanical stimuli are also demonstrated with the multipixel electronic skin. The stress-strain behavior of the hybrid structure is investigated by finite element analysis to elucidate the underlying principle of the superior sensing performance of the electronic skin.

7α,15-Dihydroxydehydroabietic acid from Pinus koraiensis inhibits the promotion of angiogenesis through downregulation of VEGF, p-Akt and p-ERK in HUVECs.

Pinus koraiensis pinecones are considered an undesired waste by-product of the processing of seeds. However, recent studies of the potential anti-tumor effects of the pinecones have led to increasing interest in their chemical constituents. The present study examined the potential antiangiogenic effects of the constituents of pinecones and further characterized their underlying mechanisms of action. Chemical investigation of a water extract of P. koraiensis pinecones led to the isolation and identification of the eight main components including five diterpenoids (1-5), two monoterpenes (6,7) and a phenolic acid (8). The structure of the compounds was determined by spectroscopic analysis of NMR spectra and LC/MS analysis. Of the isolated compounds, 7α,15-dihydroxydehydroabietic acid (5) significantly inhibited the promotion of angiogenesis in human umbilical vein endothelial cells (HUVECs). Compound 5 inhibited angiogenesis through downregulation of the VEGF, p-Akt and p-ERK signaling pathways. These results provide experimental evidence of a novel biological activity of 7α,15-dihydroxydehydroabietic acid (5) as a potential antiangiogenic substance. This study also suggests that compound 5 could potentially be a useful adjuvant therapeutic substance for cancer prevention and treatment.

Diketopiperazines from Costa Rican endolichenic fungus Colpoma sp. CR1465A.

Three new diketopiperazines (1-3), cyclo(l-Pro-d-trans-Hyp) (1), cyclo(l-Pro-d-Glu) (2), and cyclo(d-Pro-d-Glu) (3) and five known diketopiperazines (4-8) were isolated from the endolichenic fungus Colpoma sp. CR1465A identified from the Costa Rican plant Henriettea tuberculosa (Melatomataceae). The structures of the new compounds 1-3 were elucidated using a combination of extensive spectroscopic analyses, including 2D NMR and HR-MS, and their absolute configurations were determined by a combination of NOESY analysis and Marfey's method. Cyclo(l-Pro-d-allo-Thr) (4) was recently isolated from a South China Sea marine sponge Callyspongia sp., but its NMR spectroscopic data were not reported, and cyclo(l-Pro-l-Asp) (5) was previously reported but only as a synthetic product. The NMR data assignments of compounds 4 and 5 are reported for the first time. All of the isolated compounds were tested for antifungal and antimicrobial properties.

Fabrication of aligned nanofibers by electric-field-controlled electrospinning: insulating-block method.

Aligned nanofiber arrays and mats were fabricated with an electrospinning process by manipulating the electric field. The electric field was modified by insulating blocks (IBs) that were installed between the nozzle and the substrate as guiding elements to control the trajectory of the electrospinning jet flow. Simulation results showed that the electric field was deformed near the IBs, resulting in confinement of the electrospinning jet between the blocks. The balance of the electric field in the vertical direction and the repulsive force by space charges in the confined electrified jet stream was attributed to the aligned motion of the jet. Aligned arrays of 200 nm thick polyethylene oxide nanofibers were obtained, exhibiting wave-shaped and cross patterns as well as rectilinear patterns. In addition, 40 µm thick quasi-aligned carbon-nanofiber mats with anisotropic electrical property were also attained by this method.

Highly durable and unidirectionally stooped polymeric nanohairs for gecko-like dry adhesive.

Gecko-like dry adhesive using high aspect ratio polymeric nanohairs has insuperable limitations, although it has huge potential in many applications. Repeated harsh contacts on a target substrate lead to physical collapse of nanohairs and significant degradation of the adhesion property, because the polymeric nanohairs are quite fragile due to poor mechanical robustness. Herein, we demonstrate a highly robust gecko-like dry adhesive with unidirectionally stooped polymeric nanohairs (diameter 100 nm) with a high aspect ratio (∼9) using an ultrathin metal coating. 100 cycles of repeated adhesion tests with 1 N preloading force did not significantly degrade adhesion or cause collapse of nanohairs. We believe that this approach allows gecko-like dry adhesive to be utilized in many related applications and diverse industry interests.

Dental Hetero-Graft Materials with Nano Hydroxyapatite Surface Treatment.

We report the development of hydroxyapatite nanoparticle (HAp NP)-functionalized hetero-graft materials (HGMs) for dental applications. These HGMs were prepared by attaching platelet-, needle-, and sphere-shaped HAp NPs to the surface of xenograft materials through chemical conjugation. Although all three HAp NPs contributed to increase the surface area of bone graft material (BGM), the shape of the HAp NPs was a determining factor. Platelet HAp NPs were most effective, because they caused a 48.9% increase in BGM surface area whereas the influence of the spherical NP was only a 6.7% increase. This suggests that geometric factors regarding both the attached HAp NPs and graft material surface are essential in controlling the surface roughness of graft materials. Among the three HAp NPs, it was the platelet HAp NPs that helped to increase the efficacy of the BGM most significantly. Compared with BGM with no HAp NP attachment, HGM with platelet HAp NP ('platelet-HGM) treatment had ~46.1% higher cell attachment and proliferation rate. The MTT assay also showed that the HAp NP-treated hetero-graft materials had negligible cytotoxicity.