Soap Film Transfer Printing for Ultrathin Electronics.

Flexible and stretchable electronics have attractive applications inaccessible to conventional rigid electronics. However, the mainstream transfer printing techniques have challenges for electronic films in terms of thickness and size and limitations for target substrates in terms of curvature, depth, and interfacial adhesion. Here a facile, damage-free, and contamination-free soap film transfer printing technique is reported that enables the wrinkle-free transfer of ultrathin electronic films, precise alignment in a transparent manner, and conformal and adhesion-independent printing onto various substrates, including those too topographically and adhesively challenging by existing methods. In principle, not only the pattern, resolution, and thickness of transferred films, but also the curvature, depth, and adhesion of target substrates are unlimited, while the size of transferred films can be as high as meter-scale. To demonstrate the capabilities of soap film transfer printing, pre-fabricated ultrathin electronics with multiple patterns, single micron resolution, sub-micron thickness, and centimeter size are conformably integrated onto the ultrathin web, ultra-soft cotton, DVD-R disk with the minimum radius of curvature of 131 nm, interior cavity of Klein bottle and dandelion with ultralow adhesion. The printed ultrathin sensors show superior conformabilities and robust adhesion, leading to engineering opportunities including electrocardiogram (ECG) signal acquisition and temperature measurement in aqueous environments.

Bioinspired Environment-Adaptable and Ultrasensitive Multifunctional Electronic Skin for Human Healthcare and Robotic Sensations.

Multifunctional electronic skins (e-skins) that can sense various stimuli have demonstrated increasing potential in many fields. However, most e-skins are human-oriented that cannot work in hash environments such as high temperature, underwater, and corrosive chemicals, impairing their applications, especially in human-machine interfaces, intelligent machines, robotics, and so on. Inspired by the crack-shaped sensory organs of spiders, an environmentally robust and ultrasensitive multifunctional e-skin is developed. By developing a polyimide-based metal crack-localization strategy, the device has excellent environment adaptability since polyimide has high thermal stability and chemical durability. The localized cracked part serves as an ultrasensitive strain sensing unit, while the non-cracked serpentine part is solely responsible for temperature. Since the two units are made of the same material and process, the signals are decoupled easily. The proposed device is the first multifunctional e-skin that can be used in harsh environments, therefore is of great potential for both human and robot-oriented applications.

Nanoengineering Ultrathin Flexible Pressure Sensor with Superior Sensitivity and Perfect Conformability.

Flexible pressure sensors play an increasingly important role in a wide range of applications such as human health monitoring, soft robotics, and human-machine interfaces. To achieve a high sensitivity, a conventional approach is introducing microstructures to engineer the internal geometry of the sensor. However, this microengineering strategy requires the sensor's thickness to be typically at hundreds to thousands of microns level, impairing the sensor's conformability on surfaces with microscale roughness like human skin. In this manuscript, a nanoengineering strategy is pioneered that paves a path to resolve the conflicts between sensitivity and conformability. A dual-sacrificial-layer method is initiated that facilitates ease of fabrication and precise assembly of two functional nanomembranes to manufacture the thinnest resistive pressure sensor with a total thickness of ≈850 nm that achieves perfectly conformable contact to human skin. For the first time, the superior deformability of the nanothin electrode layer on a carbon nanotube conductive layer is utilized by the authors to achieve a superior sensitivity (92.11 kPa-1 ) and an ultralow detection limit (<0.8 Pa). This work offers a new strategy that is able to overcome a key bottleneck for current pressure sensors, therefore is of potential to inspire the research community for a new wave of breakthroughs.

Five New Phenylpropanoyl Phloroglucinol Derivatives from Leptospermum scoparium.

Leptosperols C-G (1-5), five new phenylpropanoyl phloroglucinol derivatives were isolated from the leaves of Leptospermum scoparium. Compounds 1-3 are phenylpropanoyl phloroglucinol-sesquiterpene adducts with new carbon skeletons. Their structures with absolute configurations were elucidated by detailed spectroscopic analyses, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculation. Compounds 2 and 3 exhibited moderate anti-inflammatory activity in zebrafish acute inflammatory models.

Wearable Self-Powered Smart Sensors for Portable Nutrition Monitoring.

Self-powered sensors have attracted great attention in the field of analysis owing to the necessity of power resources for the routine use of sensor devices. However, it is still challenging to construct wearable self-powered sensors in a simple and efficient way. Herein, wearable self-powered textile smart sensors based on advanced bifunctional polyaniline/reduced graphene oxide (PANI/RGO) films have been successfully developed for remote real-time detection of vitamin C. Specifically, a pH-assisted oil/water (O/W) self-assembly strategy was proposed to boost the O/W self-assembled PANI/RGO films via proton regulation. The as-obtained PANI/RGO films could be directly loaded on the textile substrate, with good capacitive and biosensing performance due to the multifunctionality of PANI and RGO, respectively. Moreover, both wearable power supply devices and wearable biosensors based on PANI/RGO films possess good electrochemical performance, which paves the way for the actual application of self-powered nutrition monitoring. Significantly, obvious signals have been obtained in the detection of vitamin C beverages, exhibiting promising application values in daily nutrition track necessities. Prospectively, this study would provide an effective and simple strategy for integrating wearable self-powered sensors, and the developed smart sensing system is an ideal choice for the portable detection of nutrition.

Screening of Bufadienolides from Toad Venom Identifies Gammabufotalin as a Potential Anti-inflammatory Agent.

Toad venom (Chansu) is used in the treatment of infectious and inflammatory diseases in China and East/Southeast Asian countries. However, the anti-inflammatory components of toad venom have not yet been systematically evaluated and clearly defined. To investigate the anti-inflammatory effects of toad venom and identify new anti-inflammatory ingredients, we used zebrafish, an alternative drug screening model, to evaluate the anti-inflammatory effects of 14 bufadienolides previously isolated from toad venom. Most of the bufadienolides were found to exert significant anti-inflammatory effects on lipopolysaccharide-, CuSO4-, or tail transection-induced zebrafish inflammatory models. Moreover, gammabufotalin ( 6: ) inhibits lipopolysaccharide-induced inflammation by suppressing the myeloid differentiation primary response 88/nuclear factor-kappa B and STAT3 signal pathways. This study confirms the potential of zebrafish in drug screening, clarifies the anti-inflammatory effects of bufadienolides from toad venom, and indicates that gammabufotalin may be developed as a novel therapeutic agent for inflammatory diseases in the future.

Loading a High-Viscous Droplet via the Cone-Shaped Liquid Bridge Induced by an Electrostatic Force.

In transfer printing, the loaded droplet on the probe has a significant influence on the dispensing resolution. A suitable loading approach for a high-viscous liquid is highly required. Herein, a novel electrostatic loading method is presented, in which the main aim is to control precisely the formation and breaking of a cone-shaped liquid bridge. An experimental device is developed. The influence of electrical and geometric parameters on the feature size of the liquid bridge is investigated in detail. In the formation of the liquid bridge, the increase of voltage or the decrease of the air gap can enhance the electric field intensity, thus reducing the formation period and increasing the initial cone tip diameter of the liquid cone. After the liquid bridge is formed, both the circuit current implying the liquid wetted area on the probe surface and the lifting velocity of the probe are utilized to further regulate the volume of the loaded droplet. Loaded droplets ranging from 60 to 600 pL are obtained via the method with a standard deviation of 4 to 30 pL. Moreover, a dot array is transferred with different loaded droplets. The minimum diameter of the printed dots is about 140 µm with a variation less than 5%. The advantages include the reduced risk of contamination, the droplet-size independent of the size of the probe, and the low cost of the device.

Bufadienolides from the Eggs of the Toad Bufo bufo gargarizans and Their Antimelanoma Activities.

Toads produce potent toxins, named bufadienolides, to defend against their predators. Pharmacological research has revealed that bufadienolides are potential anticancer drugs. In this research, we reported nine bufadienolides from the eggs of the toad Bufo bufo gargarizans, including two new compounds (1 and 3). The chemical structures of 1 and 3, as well as of one previously reported semisynthesized compound (2), were elucidated on the basis of extensive spectroscopic data interpretation, chemical methods, and X-ray diffraction analysis. Compound 1 is an unusual 19-norbufadienolide with rearranged A/B rings. A biological test revealed that compounds 2 and 4-8 showed potent cytotoxic activities toward human melanoma cell line SK-MEL-1 with IC50 values less than 1.0 µM. A preliminary mechanism investigation revealed that the most potent compound, 8, could induce apoptosis via PARP cleavage, while 5 and 6 significantly suppressed angiogenesis in zebrafish. Furthermore, an in vivo biological study showed that 5, 6, and 8 inhibit SK-MEL-1 cell growth significantly.

Monoterpenoid indole alkaloids from the fruits of Gelsemium elegans and their anti-inflammatory activities.

Two novel monoterpenoid indole alkaloids (MIAs), gelsechizines A-B (1-2), along with four known ones (3-6) were isolated from the fruits of Gelsemium elegans. Compound 1 features a new carbon skeleton with two additional carbon atoms forming a 4-methylpyridine unit. Their structures with absolute configurations were elucidated by NMR, MS, X-ray diffraction and electronic circular dichroism (ECD) calculations. Compounds 1-3 showed significant anti-inflammatory effects in vivo and in vitro, which may be related to the inhibition of the trecruitment of neutrophils and macrophages as well as the secretion of TNF-α and IL-6. Preliminary structure-activity relationship analysis revealed that the ß-N-acrylate moiety plays an important role in the anti-inflammatory effect.

Asymmetric Total Synthesis of Bufospirostenin A.

The first and asymmetric total synthesis of bioactive bufospirostenin A, an unusual spirostanol with rearranged A/B rings, was accomplished. The synthetically challenging [5-7-6-5] tetracyclic ring system, found in bufospirostenin A and some other natural products, was efficiently constructed by the unique intramolecular rhodium-catalyzed Pauson-Khand reaction of an alkoxyallene-yne. The 11 stereocenters in the final product, including the 10 contiguous stereocenters, were installed diastereoselectively.

Forsythoside A inhibits adhesion and migration of monocytes to type II alveolar epithelial cells in lipopolysaccharide-induced acute lung injury through upregulating miR-124.

Acute lung injury (ALI) is a severe disease for which effective drugs are still lacking at present. Forsythia suspensa is a traditional Chinese medicine commonly used to relieve respiratory symptoms in China, but its functional mechanisms remain unclear. Therefore, forsythoside A (FA), the active constituent of F. suspensa, was studied in the present study. Inflammation models of type II alveolar epithelial MLE-12 cells and BALB/c mice stimulated by lipopolysaccharide (LPS) were established to explore the effects of FA on ALI and the underlying mechanisms. We found that FA inhibited the production of monocyte chemoattractant protein-1 (MCP-1/CCL2) in LPS-stimulated MLE-12 cells in a dose-dependent manner. Moreover, FA decreased the adhesion and migration of monocytes to MLE-12 cells. Furthermore, miR-124 expression was upregulated after FA treatment. The luciferase report assay showed that miR-124 mimic reduced the activity of CCL2 in MLE-12 cells. However, the inhibitory effects of FA on CCL2 expression and monocyte adhesion and migration to MLE-12 cells were counteracted by treatment with a miR-124 inhibitor. Critically, FA ameliorated LPS-induced pathological damage, decreased the serum levels of tumor necrosis factor-α and interleukin-6, and inhibited CCL2 secretion and macrophage infiltration in lungs in ALI mice. Meanwhile, administration of miR-124 inhibitor attenuated the protective effects of FA. The present study suggests that FA attenuates LPS-induced adhesion and migration of monocytes to type II alveolar epithelial cells though upregulating miR-124, thereby inhibiting the expression of CCL2. These findings indicate that the potential application of FA is promising and that miR-124 mimics could also be used in the treatment of ALI.

Forsythoside A protects against lipopolysaccharide-induced acute lung injury through up-regulating microRNA-124.

Acute lung injury (ALI) is a life-threatening disease without effective pharmacotherapies, so far. Forsythia suspensa is frequently used in the treatment of lung infection in traditional Chinese medicine. In search for natural anti-inflammatory components, the activity and the underlying mechanism of Forsythoside A (FA) from Forsythia suspensa were explored. In the present paper, BALB/c mice and murine RAW 264.7 cells were stimulated by LPS to establish inflammation models. Data showed that FA inhibited the production of TNF-α and IL-6 and the activation of STAT3 in LPS-stimulated RAW 264.7 cells. Additionally, FA increased the expression level of microRNA-124 (miR-124). Furthermore, the inhibitory effect of FA on STAT3 was counteracted by the treatment of miR-124 inhibitor. Critically, FA ameliorated LPS-induced ALI pathological damage, the increase in lung water content and inflammatory cytokine, cells infiltration and activation of the STAT3 signaling pathway in BALB/c mice. Meanwhile, FA up-regulated the expression of miR-124 in lungs, while administration with miR-124 inhibitor attenuated the protective effects of FA. Our results indicated that FA alleviates LPS-induced inflammation through up-regulating miR-124 in vitro and in vivo. These findings indicate the potential of FA and miR-124 in the treatment of ALI.

Two New Isomeric Andrographolides with Anti-Inflammatory and Cytotoxic Activity.

Two novel epimerized andrographolides, 8,17-dihydro-7,8-dehydroandrographolide and 10ß-8,17-dihydro-7,8-dehydroandrographolide, were isolated from andrographolide sulfonates. Their structures were elucidated by detailed NMR analysis, single-crystal X-ray diffraction and quantum chemical ECD calculations. In addition, these compounds exhibited suppression of NO production in LPS-stimulated RAW264.7 cells over the range of 1.564 to 25.000 µg/mL.

[Determination of Aromatic Compounds Metabolites in Human Urine by Solid Phase Extraction-liquid Chromatography-Tandem Mass Spectrometry].

OBJECTIVE: To establish the method based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with solid phase extraction (SPE) for simultaneous determination of the biological metabolites of aromatic compounds, including N-acetyl-S-phenyl-L-cysteine (SPMA), N-acetyl-S-benzyl-cysteine (SBMA), p-nitrophenol (PNP), methylhippuric acids (MHA), p-Aminophenol (PAP), mandelic acid (MA), phenylglyoxylic acid (PGA) and 1-hydroxypyrene (1-OHP) in urine. METHODS: After adding 20 µL of ß-glucuronidase and 1 mL ammonium acetate buffer solution in 1 mL of urine, the sample was digested in a 37 ℃ incubator for 20 h. After digestion, the enzymatic hydrolysate was purified by PRIME HLB solid phase extraction column. The target compounds were eluted with 4 mL of acetonitrile and blown to dryness with nitrogen, reconstituted with 0.20 mL of methanol. Injected the sample solution into LC-MS/MS system for analysis after filtering with 0.22 µm filter membrane. LC separation was carried out on a reversed-phase C18 column (2.1 mm×150 mm, 3.5 µm); gradient eluting was performed at a flow rate of 0.2 mL/min. The water containing 0.1% formic acid was used as mobile phase A and methanol was used as mobile phase B. The mass spectrometry was performed with multiple reaction monitoring (MRM) mode, using alternating positive and negative ions, and internal standard curves were used for quantification. RESULTS: The eight metabolites showed good linearity within the range of 1-100 ng/mL, with a correlation coefficients greater than 0.995, and the relative precision deviation (RSDs) was 0.050%-9.95%. The method detection limits (MDLs) of the eight target metabolites were 0.041-0.12 ng/mL. The proposed method was used for urine sample analysis and the spiked recoveries were 80.1%-114.0%. CONCLUSION: The established method is quick, sensitive and accurate; it meets the requirementof the biological monitoring of aromatic compounds for the general population and occupational population.

Alopecuroides A-E, Matrine-Type Alkaloid Dimers from the Aerial Parts of Sophora alopecuroides.

Five new matrine-type alkaloid dimers, alopecuroides A-E, were isolated from the aerial parts of Sophora alopecuroides. Alopecuroides A and B represent the first dimeric matrine-type alkaloids possessing a cyano group and an epoxy moiety. Alopecuroides C and D are dimeric matrine-type alkaloids connected via C-2-C-9' and C-10-C-3' bonds, respectively. The chemical structures of alopecuroides A-E were elucidated by spectroscopic methods combined with single-crystal X-ray diffraction analysis. The anti-inflammatory effects of alopecuroides A-E were evaluated, and alopecuroide B exhibited the most significant activity, better than that of matrine, the representative compound from S. alopecuroides.

Diterpenoid Lactones with Anti-Inflammatory Effects from the Aerial Parts of Andrographis paniculata.

Andrographis paniculata (AP) has been widely used in China for centuries to treat various diseases, and especially to treat inflammation. Diterpenoid lactones are the main anti-inflammatory components of AP. However, systematic chemical composition and biological activities, as well as key pharmacophores, of these diterpenoid lactones from AP have not yet been clearly understood. In this study, 17 diterpenoid lactones, including 2 new compounds, were identified by spectroscopic methods, and most of them attenuated the generation of TNF-α and IL-6 in LPS-induced RAW 274.7 cells examined by ELISA. Pharmacophores of diterpenoid lactones responsible for the anti-inflammatory activities were revealed based on the quantitative structure-activity relationship (QSAR) models. Moreover, new compounds (AP-1 and AP-4) exerted anti-inflammatory activity in LPS microinjection-induced zebrafish, which might be correlated with the inhibition of the translocation of NF-κB p65 from cytoplasm to nucleus. Our study provides guidelines for future structure modification and rational drug design of diterpenoid lactones with anti-inflammatory properties in medical chemistry.

Arenobufagin induces MCF-7 cell apoptosis by promoting JNK-mediated multisite phosphorylation of Yes-associated protein.

BACKGROUND: It has been demonstrated that bufadienolides exert potent anti-cancer activity in various tumor types. However, the mechanisms that underlie their anti-cancer properties remain unclear. Yes-associated protein, a key effector of Hippo signaling, functions as a transcription coactivator, plays oncogenic and tumor suppressor roles under different conditions. Here, we report that arenobufagin (ABF), a representative bufadienolide, induced breast cancer MCF-7 cells to undergo apoptosis, which occurred through the JNK-mediated multisite phosphorylation of YAP. METHODS: Cytotoxicity was examined using an MTT assay. ABF-induced apoptosis was measured with a TUNEL assay and Annexin V-FITC/PI double staining assay. Western blotting, immunofluorescence, qRT-PCR and coimmunoprecipitation were employed to assess the expression levels of the indicated molecules. Lose-of-function experiments were carried out with siRNA transfection and pharmacological inhibitors. ABF-induced phosphopeptides were enriched with Ti4+-IMAC chromatography and further subjected to reverse-phase nano-LC-MS/MS analysis. RESULTS: ABF significantly reduced the viability of MCF-7 cells and increased the percentage of early and late apoptotic cells in a concentration- and time-dependent manner. Following ABF treatment, YAP accumulated in the nucleus and bound to p73, which enhanced the transcription of the pro-apoptotic genes Bax and p53AIP1. YAP knock-down significantly attenuated ABF-induced apoptotic cell death. Importantly, we found that the mobility shift of YAP was derived from its phosphorylation at multiple sites, including Tyr357. Moreover, mass spectrometry analysis identified 19 potential phosphorylation sites in YAP, with a distribution of 14 phosphoserine and 5 phosphothreonine residues. Furthermore, we found that the JNK inhibitor SP600125 completely diminished the mobility shift of YAP and its phosphorylation at Tyr357, the binding of YAP and p73, the transcription of Bax and p53AIP1 as well as the apoptosis induced by ABF. These data indicate that ABF induced YAP multisite phosphorylation, which was associated with p73 binding, and that apoptosis was mediated by the JNK signaling pathway. CONCLUSIONS: Our data demonstrate that ABF suppresses MCF-7 breast cancer proliferation by triggering the pro-apoptotic activity of YAP, which is mediated by JNK signaling-induced YAP multisite phosphorylation as well as its association with p73. The present work not only provides additional information on the use of ABF as an anti-breast cancer drug, but also offers evidence that the induction of the tumor suppressor role of YAP may be a therapeutic strategy.

Size-dependent Young's modulus in ZnO nanowires with strong surface atomic bonds.

The mechanical properties of size-dependent nanowires are important in nano-electro-mechanical systems (NEMSs), and have attracted much research interest. Characterization of the size effect of nanowires in atmosphere directly to broaden their practical application instead of just in high vacuum situations, as reported previously, is desperately needed. In this study, we systematically studied the Young's modulus of vertical ZnO nanowires in atmosphere. The diameters ranged from 48 nm to 239 nm with a resonance method using non-contact atomic force microscopy. The values of Young's modulus in atmosphere present extremely strong increasing tendency with decreasing diameter of nanowire due to stronger surface atomic bonds compared with that in vacuum. A core-shell model for nanowires is proposed to explore the Young's modulus enhancement in atmosphere, which is correlated with atoms of oxygen occurring near the nanowire surface. The modified model is more accurate for analyzing the mechanical behavior of nanowires in atmosphere compared with the model in vacuum. Furthermore, it is possible to use this characterization method to measure the size-related elastic properties of similar wire-sharp nanomaterials in atmosphere and estimate the corresponding mechanical behavior. The study of the size-dependent Young's modulus in ZnO nanowires in atmosphere will improve the understanding of the mechanical properties of nanomaterials as well as providing guidance for applications in NEMSs, nanogenerators, biosensors and other related areas.

Casticin prevents DSS induced ulcerative colitis in mice through inhibitions of NF-κB pathway and ROS signaling.

Casticin, a compound purified from the Chinese herb Viticis Fructus, has been proven effective in preventing tumor progression in previous studies. Ulcerative colitis (UC) is a common inflammatory bowel disease that affects millions of people worldwide, but no effective and safe drugs are available. In this study, we aimed to study how did casticin affect UC by evaluating its effects on dextran sulfate sodium (DSS)-induced colitis in mice. Our data suggested that casticin attenuated body weight loss, colon length shortening, and pathological damage in the colon of DSS-treated mice. Casticin decreased reactive oxygen species level and chemocytokines (IL-1ß, IL-6, TNF-α) productions in colon tissue. The decreased reactive oxygen species level and suppressed proinflammatory cytokines productions were also confirmed in casticin-treated LPS-stimulated RAW264.7 cells and hydrogen peroxide-treated CACO-2 cells in vitro. Mechanistically, casticin treatment prevented the profound activation of AKT signaling caused by DSS administration. And casticin inhibited the productions of proinflammatory chemocytokines through downregulating AKT/NF-κB pathway in macrophages. Meanwhile, data revealed that casticin increased expressions of endogenous antioxidants peroxiredoxin 3 and MnSOD were through activation in FOXO3α signaling by downregulating AKT signaling in colon epithelium cells. Our findings demonstrated that casticin alleviated DSS-induced UC by increasing the antioxidant enzyme peroxiredoxin 3 and MnSOD expressions, and decreasing the production of proinflammatory chemocytokines through inhibition of AKT signaling.