A PDE1 inhibitor reduces adipogenesis in mice via regulation of lipolysis and adipogenic cell signaling.

Vinpocetine, a phosphodiesterase (PDE) type-1 inhibitor, increases cAMP and cGMP levels and is currently used for the management of cerebrovascular disorders, such as stroke, cerebral hemorrhage, and cognitive dysfunctions. In this study, we first determined that vinpocetine effectively suppressed adipogenesis and lipid accumulation. However, we questioned which molecular mechanism is involved because the role of PDE in adipogenesis is still controversial. Vinpocetine decreased adipogenic cell signaling, including the phosphorylation of ERK, AKT, JAK2, and STAT3, and adipokine secretion, including IL-6, IL-10, and IFN-α. Interestingly, vinpocetine increased the phosphorylation of HSL, suggesting the induction of the lipolysis pathway. Moreover, vinpocetine increased UCP1 expression via increasing cAMP and PKA phosphorylation. The administration of vinpocetine with a normal-chow diet (NFD) or a high-fat diet (HFD) in mice attenuated body weight gain in mice fed both the NFD and HFD. These effects were larger in the HFD-fed mice, without a difference in food intake. Vinpocetine drastically decreased fat weight and adipocyte cell sizes in gonadal and inguinal white adipose tissues and in the liver in both diet groups. Serum triacylglycerol levels and fasting blood glucose levels were reduced by vinpocetine treatment. This study suggested that vinpocetine prevents adipocyte differentiation through the inhibition of adipogenesis-associated cell signaling in the early stages of adipogenesis. Moreover, upregulating cAMP levels leads to an increase in lipolysis and UCP1 expression and then inhibits lipid accumulation. Therefore, we suggest that vinpocetine could be an effective agent for treating obesity, as well as improving cognition and cardiovascular function in older individuals.

Shaping nanoparticle fingerprints at the interface of cholesteric droplets.

The ordering of nanoparticles into predetermined configurations is of importance to the design of advanced technologies. Here, we balance the interfacial energy of nanoparticles against the elastic energy of cholesteric liquid crystals to dynamically shape nanoparticle assemblies at a fluid interface. By adjusting the concentration of surfactant that plays the dual role of tuning the degree of nanoparticle hydrophobicity and altering the molecular anchoring of liquid crystals, we pattern nanoparticles at the interface of cholesteric liquid crystal emulsions. In this system, interfacial assembly is tempered by elastic patterns that arise from the geometric frustration of confined cholesterics. Patterns are tunable by varying both surfactant and chiral dopant concentrations. Adjusting the particle hydrophobicity more finely by regulating the surfactant concentration and solution pH further modifies the rigidity of assemblies, giving rise to surprising assembly dynamics dictated by the underlying elasticity of the cholesteric. Because particle assembly occurs at the interface with the desired structures exposed to the surrounding water solution, we demonstrate that particles can be readily cross-linked and manipulated, forming structures that retain their shape under external perturbations. This study serves as a foundation for better understanding inter-nanoparticle interactions at interfaces by tempering their assembly with elasticity and for creating materials with chemical heterogeneity and linear, periodic structures, essential for optical and energy applications.

Multistate and On-Demand Smart Windows.

Composite films consisting of wrinkles on top of the elastomeric poly(dimethylsiloxane) film and a thin layer of silica particles embedded at the bottom is prepared as on-demand mechanoresponsive smart windows. By carefully varying the wrinkle geometry, silica particle size, and stretching strain, different initial optical states and a large degree of optical transmittance change in the visible to near infrared range with a relatively small strain (as small as 10%) is achieved. The 10% pre-strain sample has shallow wrinkles with a low amplitude and shows moderate transmittance (60.5%) initially and the highest transmittance of 86.4% at 550 nm when stretched at the pre-strain level. Stretching beyond the pre-strain level leads to a drastic decrease of the transmittance at 550 nm, 39.7% and 70.8% with an additional 10% and 30% strain, respectively. The large drop of optical transmittance is the result of combined effects from the formation of secondary wrinkles and nanovoids generated around the particles. The 20% pre-strain sample has wrinkles with a moderate amplitude, showing 36.9% transmittance in the initial state, and the highest transmittance of 71.5% at 550 nm when stretched to the pre-strain level. Further stretching leads to increased opacity similar to that seen from the 10% pre-strain sample.

Geometric Design of Scalable Forward Scatterers for Optimally Efficient Solar Transformers.

It will be ideal to deliver equal, optimally efficient "doses" of sunlight to all cells in a photobioreactor system, while simultaneously utilizing the entire solar resource. Backed by the numerical scattering simulation and optimization, here, the design, synthesis, and characterization of the synthetic iridocytes that recapitulated the salient forward-scattering behavior of the Tridacnid clam system are reported, which presents the first geometric solution to allow narrow, precise forward redistribution of flux, utilizing the solar resource at the maximum quantum efficiency possible in living cells. The synthetic iridocytes are composed of silica nanoparticles in microspheres embedded in gelatin, both are low refractive index materials and inexpensive. They show wavelength selectivity, have little loss (the back-scattering intensity is reduced to less than ≈0.01% of the forward-scattered intensity), and narrow forward scattering cone similar to giant clams. Moreover, by comparing experiments and theoretical calculation, it is confirmed that the nonuniformity of the scatter sizes is a "feature not a bug" of the design, allowing for efficient, forward redistribution of solar flux in a micrometer-scaled paradigm. This method is environmentally benign, inexpensive, and scalable to produce optical components that will find uses in efficiency-limited solar conversion technologies, heat sinks, and biofuel production.

Development of zebrafish medulloblastoma-like PNET model by TALEN-mediated somatic gene inactivation.

Genetically engineered animal tumor models have traditionally been generated by the gain of single or multiple oncogenes or the loss of tumor suppressor genes; however, the development of live animal models has been difficult given that cancer phenotypes are generally induced by somatic mutation rather than by germline genetic inactivation. In this study, we developed somatically mutated tumor models using TALEN-mediated somatic gene inactivation of cdkn2a/b or rb1 tumor suppressor genes in zebrafish. One-cell stage injection of cdkn2a/b-TALEN mRNA resulted in malignant peripheral nerve sheath tumors with high frequency (about 39%) and early onset (about 35 weeks of age) in F0 tp53e7/e7 mutant zebrafish. Injection of rb1-TALEN mRNA also led to the formation of brain tumors at high frequency (58%, 31 weeks of age) in F0 tp53e7/e7 mutant zebrafish. Analysis of each tumor induced by somatic inactivation showed that the targeted genes had bi-allelic mutations. Tumors induced by rb1 somatic inactivation were characterized as medulloblastoma-like primitive neuroectodermal tumors based on incidence location, histopathological features, and immunohistochemical tests. In addition, 3' mRNA Quanti-Seq analysis showed differential activation of genes involved in cell cycle, DNA replication, and protein synthesis; especially, genes involved in neuronal development were up-regulated.

REP1 Modulates Autophagy and Macropinocytosis to Enhance Cancer Cell Survival.

Rab escort protein 1 (REP1), a component of the Rab geranyl-geranyltransferase 2 complex, plays a role in Rab protein recruitment in proper vesicles during vesicle trafficking. In addition to having well-known tissue degenerative phenotypes in the REP1 mutant, REP1 is tightly associated with cancer development and contributes to cell growth and survival. However, the functional mechanism of REP1 in cancer progression is largely uninvestigated. Here, we show that REP1 plays a crucial role in regulating mammalian target of rapamycin (mTOR) signaling and its downstream pathways, as well as autophagy and macropinocytosis, which are essential for cancer cell survival during metabolic stresses including starvation. REP1 small interfering RNA (siRNA) treatment downregulates mTORC1 activity in growing media, but blocks autophagosome formation under nutrient-depleted conditions. In contrast to the mild decrease of lysosomal enzyme activity seen in REP1 depletion, in REP1 knockdown the subcellular localization of lysosomes is altered, and localization of REP1 itself is modulated by intracellular nutrient levels and mTOR activity. Furthermore, REP1 depletion increases macro pinocytosis which may be a feedback mechanism to compensate autophagy inhibition. Concomitant treatment with macropinocytosis inhibitor and REP1siRNAresults in more significant cell death than autophagy blockade with REP1 knockdown. Therefore, REP1-mediated autophagy and lysosomal degradation processes act as novel regulatory mechanisms to support cancer cell survival, which can be further investigated as a potential cancer-targeting pathway.

Varying and unchanging whiteness on the wings of dusk-active and shade-inhabiting Carystoides escalantei butterflies.

Whiteness, although frequently apparent on the wings, legs, antennae, or bodies of many species of moths and butterflies, along with other colors and shades, has often escaped our attention. Here, we investigate the nanostructure and microstructure of white spots on the wings of Carystoides escalantei, a dusk-active and shade-inhabiting Costa Rican rain forest butterfly (Hesperiidae). On both males and females, two types of whiteness occur: angle dependent (dull or bright) and angle independent, which differ in the microstructure, orientation, and associated properties of their scales. Some spots on the male wings are absent from the female wings. Whether the angle-dependent whiteness is bright or dull depends on the observation directions. The angle-dependent scales also show enhanced retro-reflection. We speculate that the biological functions and evolution of Carystoides spot patterns, scale structures, and their varying whiteness are adaptations to butterfly's low light habitat and to airflow experienced on the wing base vs. wing tip.

Fine Golden Rings: Tunable Surface Plasmon Resonance from Assembled Nanorods in Topological Defects of Liquid Crystals.

Unprecedented, reversible, and dynamic control over an assembly of gold nanorods dispersed in liquid crystals (LC) is demonstrated. The LC director field is dynamically tuned at the nanoscale using microscale ring confinement through the interplay of elastic energy at different temperatures, thus fine-tuning its core replacement energy to reversibly sequester nanoscale inclusions at the microscale. This leads to shifts of 100 nm or more in the surface plasmon resonance peak, an order of magnitude greater than any previous work with AuNR composites.

Smectic Gardening on Curved Landscapes.

Focal conic domains (FCDs) form in smectic-A liquid crystal films with hybrid anchoring conditions with eccentricity and size distribution that depend strongly on interface curvature. Assemblies of FCDs can be exploited in settings ranging from optics to material assembly. Here, using micropost arrays with different shapes and arrangement, we assemble arrays of smectic flower patterns, revealing their internal structure as well as defect size, location, and distribution as a function of interface curvature, by imposing positive, negative, or zero Gaussian curvature at the free surface. We characterize these structures, relating free surface topography, substrate anchoring strength, and FCD distribution. Whereas the largest FCDs are located in the thickest regions of the films, the distribution of sizes is not trivially related to height, due to Apollonian tiling. Finally, we mold FCDs around microposts of complex shape and find that FCD arrangements are perturbed near the posts, but are qualitatively similar far from the posts where the details of the confining walls and associated curvature fields decay. This ability to mold FCD defects into a variety of hierarchical assemblies by manipulating the interface curvature paves the way to create new optical devices, such as compound eyes, via a directed assembly scheme.

Characterization of charge transport properties of a 3D electrode for dye-sensitized solar cells.

Electron transport and recombination in three-dimensionally-ordered (3D-ordered) structure electrodes were investigated using intensity-modulated photocurrent and photovoltage spectroscopy. The surface-modified TiO2 inverse opal structure was applied as a 3D electrode. The morphology, crystalline structure and surface states of the 3D-ordered structure were characterized by SEM, TEM and XPS and compared to those of the conventional nanoparticulate TiO2 structure. The performance of the 3D electrode was also evaluated by comparing the transport time and recombination lifetime to those of the conventional electrodes. Remarkably, the recombination lifetime in inverse opal was found to be greater than in nanocrystalline TiO2 by 4.3-6.2 times, thus improving the electron collection efficiency by 10%. Comparing the photovoltaic performance, although the dye adsorption of the 3D-ordered porous electrode is lower, the electrode achieves a photocurrent density comparable to that of a nanoparticulate TiO2 electrode due to the higher light scattering as well as the higher collection efficiency.

Graphene-embedded 3D TiO2 inverse opal electrodes for highly efficient dye-sensitized solar cells: morphological characteristics and photocurrent enhancement.

We demonstrated the preparation of graphene-embedded 3D inverse opal electrodes for use in DSSCs. The graphene was incorporated locally into the top layers of the inverse opal structures and was embedded into the TiO2 matrix via post-treatment of the TiO2 precursors. DSSCs comprising the bare and 1-5 wt% graphene-incorporated TiO2 inverse opal electrodes were compared. We observed that the local arrangement of graphene sheets effectively enhanced electron transport without significantly reducing light harvesting by the dye molecules. A high efficiency of 7.5% was achieved in DSSCs prepared with the 3 wt% graphene-incorporated TiO2 inverse opal electrodes, constituting a 50% increase over the efficiencies of DSSCs prepared without graphene. The increase in efficiency was mainly attributed to an increase in J(SC), as determined by the photovoltaic parameters and the electrochemical impedance spectroscopy analysis.

Enhanced photovoltaic properties of Nb2O5-coated TiO2 3D ordered porous electrodes in dye-sensitized solar cells.

This paper describes the use of Nb2O5-coated TiO2 3D ordered porous electrodes in dye-sensitized solar cells. We employed bilayer inverse opal structures as a backbone of 3D porous structures, and the number of Nb2O5 coatings was controlled, determining the concentration of Nb2O5 coating. XPS measurements confirmed the formation of Nb2O5. The uniformity of the Nb2O5 coating was characterized by elemental mapping using SEM and TEM measurements. Photovoltaic measurement on dye-sensitized solar cells (DSSCs) that incorporated Nb2O5/TiO2 inverse opal electrodes yielded a maximum efficiency of 7.23% for a 3.3 wt % Nb2O5 coating on a TiO2 IO structure. The Nb2O5 significantly increased the short-circuit current density (J(SC)). Electrochemical impedance spectroscopy was used to measure the J(SC), revealing an enhanced electron injection upon deposition of the Nb2O5 coating.

Bottom-up growth of hierarchical electrodes for highly efficient dye-sensitized solar cells.

The nonconventional bottom-up growth of TiO2 was first demonstrated in the preparation of hierarchical TiO2 electrodes for use in highly efficient dye-sensitized solar cells. The simple immersion of a substrate in a precursor solution enabled the growth of TiO2 particulate films. Here, we have implemented a hierarchical growth strategy in which two stages of controlled growth yielded first macroscale TiO2 particles, followed by mesoscale TiO2 particles. We successfully fabricated electrode films up to 20 µm thick via a growth rate of 0.3 µm/min. The specific area of the electrodes was controlled via the deposition of mesoscale TiO2 particles. The deposited particles displayed a rutile phase with an average size of several tens of nanometers in diameter, as confirmed by XRD and high-resolution TEM imaging. After depositing the second layer of mesoscale TiO2 particles, the photocurrent density increased by a factor of 3. A maximum efficiency of 6.84% was obtained for the hierarchically structured TiO2 electrodes under 1 sun illumination. The hierarchical TiO2 electrodes were compared with macroporous TiO2 electrodes, revealing that the higher photocurrent density could be attributed to a longer electron recombination lifetime and a high specific area. The longer recombination lifetime was supported by the presence of fewer defective TiO2 surfaces, as confirmed by the XPS spectrum.