Mangiferin Reduces the Inhibition of Chondrogenic Differentiation by IL-1β in Mesenchymal Stem Cells from Subchondral Bone and Targets Multiple Aspects of the Smad and SOX9 Pathways

Mangiferin is a natural immunomodulator found in plants including mango trees. The effects of mangiferin on chondrogenesis and cartilage repair have not yet been reported. This study was designed to determine the effect of mangiferin on chondrogenic differentiation in IL-1β-stimulated mesenchymal stem cells (MSCs) from subchondral bone and to explore the mechanisms underlying these effects. MSCs were isolated from the subchondral bone of rabbit and treated with mangiferin alone and/or interleukin-1β (IL-1β). Mangiferin induced chondrogenic differentiation in MSCs by upregulating transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, and BMP-4 and several key markers of chondrogenesis, including sex-determining region Y–box (SRY-box) containing gene 9 (SOX9), type 2α1 collagen (Col2α1), cartilage link protein, and aggrecan. In IL-1β-stimulated MSCs, mangiferin significantly reversed the production of TGF-β, BMP-2, BMP-4, SOX9, Col2α1, cartilage link protein, and aggrecan, as well as matrix metalloproteinase (MMP)-1, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS5). Mangiferin upregulated the phosphorylation of Smad 2, Smad 3, Smad 1/5/8, and SOX9 in IL-1β-stimulated MSCs. In the presence of mangiferin, SOX9 siRNA suppressed the activation of Smad 2, Smad 3, Smad 1/5/8, aggrecan, and Col2α1 expression. In conclusion, mangiferin exhibits both chondrogenic and chondroprotective effects on damaged MSCs and mediates these effects by targeting multiple aspects of the Smad and SOX9 signaling pathways.     

Residual stress analysis of an external grooved thick-walled pressure vessel

Residual stress analysis of an autofrettaged thick-walled pressure vessel containing an external groove was described in order to calculate the stress concentration at the external groove. The autofrettage residual stress distributions of the external grooved thick-walled pressure vessel were simulated using an equivalent thermal loading from the analogy of thermal and autofrettage residual stress fields. Thermal stresses due to the simulated thermal loadings for various degrees of autofrettage overstrain level were computed using finite element methods. Very high stress concentration factors due to autofrettage loadings were obtained at the external groove root that contained a sharp root radius. Experimental measurement of residual stresses for a fully autofrettaged smooth thick-walled pressure vessel using an equivalent saw cut method resulted in very close agreement with the theoretical autofrettage residual stress distributions. The stress analysis results implied that the autofrettage residual stress concentration might cause a cracking problem at the external groove root of the thick-walled pressure vessel, indicating that lower autofrettage overstrain and a groove geometry change were desirable for enhanced durability.     

Exosome as a Vehicle for Delivery of Membrane Protein Therapeutics,PH20, for Enhanced Tumor Penetration and Antitumor Efficacy

As biochemical and functional studies of membrane protein remain a challenge, there is growing interest in the application of nanotechnology to solve the difficulties of developing membrane protein therapeutics. Exosome, composed of lipid bilayer enclosed nanosized extracellular vesicles, is a successful platform for providing a native membrane composition. This study reports an enzymatic exosome, which harbors native PH20 hyaluronidase (Exo‐PH20), which is able to penetrate deeply into tumor foci via hyaluronan degradation, allowing tumor growth inhibition and increased T cell infiltration into the tumor. This exosome‐based strategy is developed to overcome the immunosuppressive and anticancer therapy‐resistant tumor microenvironment, which is characterized by an overly accumulated extracellular matrix. Notably, this engineered exosome with the native glycosylphosphatidylinositol‐anchored form of hyaluronidase has a higher enzymatic activity than a truncated form of the recombinant protein. In addition, the exosome‐mediated codelivery of PH20 hyaluronidase and a chemotherapeutic (doxorubicin) efficiently inhibits tumor growth. This exosome is designed to degrade hyaluronan, thereby augmenting nanoparticle penetration and drug diffusion. The results thus show that this is a promising exosome‐based platform that harbors not only a membrane‐associated enzyme with high activity but also therapeutic payloads.     

Measurement of intracellular free zinc in living cortical neurons: routes of entry

We used the ratioable fluorescent dye mag-fura-5 to measure intracellular free Zn2+ ([Zn2+]i) in cultured neocortical neurons exposed to neurotoxic concentrations of Zn2+ in concert with depolarization or glutamate receptor activation and identified four routes of Zn2+ entry. Neurons exposed to extracellular Zn2+ plus high K+ responded with a peak cell body signal corresponding to a [Zn2+]i of 35-45 nM. This increase in [Zn2+]i was attenuated by concurrent addition of Gd3+, verapamil, omega-conotoxin GVIA, or nimodipine, consistent with Zn2+ entry through voltage-gated Ca2+channels. Furthermore, under conditions favoring reverse operation of the Na+-Ca2+ exchanger, Zn2+ application induced a slow increase in [Zn2+]i and outward whole-cell current sensitive to benzamil-amiloride. Thus, a second route of Zn2+ entry into neurons may be via transporter-mediated exchange with intracellular Na+. Both NMDA and kainate also induced rapid increases in neuronal [Zn2+]i. The NMDA-induced increase was only partly sensitive to Gd3+ or to removal of extracellular Na+, consistent with a third route of entry directly through NMDA receptor-gated channels. The kainate-induced increase was highly sensitive to Gd3+ or Na+ removal in most neurons but insensitive in a minority subpopulation ("cobalt-positive cells"), suggesting that a fourth route of neuronal Zn2+ entry is through the Ca2+-permeable channels gated by certain subtypes of AMPA or kainate receptors.     

TrackerBots: Autonomous unmanned aerial vehicle for real‐time localization and tracking of multiple radio‐tagged animals

Autonomous aerial robots provide new possibilities to study the habitats and behaviors of endangered species through the efficient gathering of location information at temporal and spatial granularities not possible with traditional manual survey methods. We present a novel autonomous aerial vehicle system—TrackerBots—to track and localize multiple radio‐tagged animals. The simplicity of measuring the received signal strength indicator (RSSI) values of very high frequency (VHF) radio‐collars commonly used in the field is exploited to realize a low‐cost and lightweight tracking platform suitable for integration with unmanned aerial vehicles (UAVs). Due to uncertainty and the nonlinearity of the system based on RSSI measurements, our tracking and planning approaches integrate a particle filter for tracking and localizing and a partially observable Markov decision process for dynamic path planning. This approach allows autonomous navigation of a UAV in a direction of maximum information gain to locate multiple mobile animals and reduce exploration time and, consequently, conserve on‐board battery power. We also employ the concept of search termination criteria to maximize the number of located animals within power constraints of the aerial system. We validated our real‐time and online approach through both extensive simulations and field experiments with five VHF radio‐tags on a grassland plain.     

Constructive understanding and reproduction of functions of gluteus medius by using a musculoskeletal walking robot

Several factors affect the performance of humanoid walking. One factor is the complex nature of lower limbs, especially the muscles around the pelvis that contribute significantly to the stability and adaptivity of humanoid locomotion. The significance of this muscle group assures a impact on the facility of walking robots once the nature of its contribution is understood, and it can be replicated on robots. To propose a mechanical structure that facilitates walking in robots, we realized a muscle by modeling its pelvis region like that of a humanoid and developing a musculoskeletal humanoid robot. Especially, we focused on the gluteus medius, which is important for the general stability against frontal movements of the hip. Furthermore, it passively changes its influence on such motions; this is helpful during the different phases of locomotion. These changes depend on the alignment of the pelvis and femur. We confirmed the viability of the robotic gluteus medius, which was simplified to a model of two partial muscles by accomplishing the walking using this robot. This accomplishment verifies our hypothesis that using this model, the supporting functionality for the locomotion of the muscle can be reproduced and enhances the biological plausibility.     

A finite element method for elliptic optimal control problem on a non-convex polygon with corner singularities

In this paper, we study a finite element method overcoming corner singularities for elliptic optimal control problem posed on a polygon. Based on a corner singularity decomposition of singular solution for the associated elliptic system, we derive an extraction formula for coefficients of singular parts, called stress intensity factors, and introduce a finite element discretization for regular parts of the solution pair. Furthermore, we analyze the finite element solutions in $L^2$ and $H^1$ norms. By numerical experiments, we confirm the efficiency and reliability of the proposed method.     

Ultra-Deep-Blue Aggregation-Induced Delayed Fluorescence Emitters: Achieving Nearly 16% EQE in Solution-Processed Nondoped and Doped OLEDs with CIEy < 0.1

Ultra-deep-blue aggregation-induced delayed fluorescence (AIDF) emitters (TB-tCz and TB-tPCz) bearing organoboron-based cores as acceptors and 3,6-substituted carbazoles as donors are presented. The thermally activated delayed fluorescence (TADF) properties of the two emitters are confirmed by theoretical calculations and time-resolved photoluminescence experiments. TB-tCz and TB-tPCz exhibit fast reverse intersystem crossing rate constants owing to efficient spin–orbit coupling between the singlet and triplet states. When applied in solution-processed organic light-emitting diodes (OLEDs), the TB-tCz- and TB-tPCz-based nondoped devices exhibit ultra-deep-blue emissions of 416–428 nm and high color purity owing to their narrow bandwidths of 42.2–44.4 nm, corresponding to the Commission International de l´Eclairage color coordinates of (x = 0.16–0.17, y = 0.05–0.06). They show a maximum external quantum efficiency (EQE_max) of 8.21% and 15.8%, respectively, exhibiting an unprecedented high performance in solution-processed deep-blue TADF-OLEDs. Furthermore, both emitters exhibit excellent device performances (EQE_max = 14.1–15.9%) and color purity in solution-processed doped OLEDs. The current study provides an AIDF emitter design strategy to implement high-efficiency deep-blue OLEDs in the future.     

Solar‐Driven Alkaline Water Electrolysis with Multifunctional Catalysts

Alkaline water electrolysis (AWE) holds great promise for a truly sustainable energy future if it can be driven by renewable energy sources such as solar and wind. The main challenge arises from the serious partial loading issue when intermittent and unstable renewable energy is coupled to water electrolyzers. An energy storage device can mitigate this incompatibility between water electrolyzer and renewable energy sources. Herein, an AWE device driven by solar photovoltaic (PV) through a full cell of lithium‐ion battery (LIB) as an energy reservoir is demonstrated (PV?LIB?AWE). Stable power output from LIB drives the water electrolyzer for steady hydrogen production, and thus overcomes the partial loading issue of AWE. Moreover, a multifunctional hierarchical material, porous nickel oxide decorated nitrogen‐doped carbon (NC) support, with excellent electrochemical performances for LIBs, oxygen evolution reaction (OER), and hydrogen evolution reaction (HER) for the PV?LIB?AWE system is developed. Density functional theory calculations show that the strong interaction between metal oxide and NC tailors the electronic structure and then optimizes activation energy of OER process. PV?LIB?AWE integrated system demonstrated here offers an alternative approach to drive water electrolysis with intermittent renewable energy for a truly sustainable energy future.     

Heterogeneous forest classification by creating mixed vegetation classes using EO-1 Hyperion

Hyperspectral satellite data is an efficient tool in vegetation mapping; however, previous studies indicate that classifying heterogeneous forests might be difficult. In this study, we propose a mapping method for a heterogeneous forest using the data of the Earth Observing-1 (EO-1) Hyperion supplemented by field survey. We introduced a band reduction method to raise classification accuracy of the Support Vector Machine classification algorithm and compared the results to the one reduced by principal component analysis (PCA), stepwise discriminant analysis (SDA), and the original data set. We also used a modified version of the Vegetation–Impervious–Soil model to create mixed vegetation classes consisting of the commonly mixing species in the area and classified them using Decision Tree classification method. We managed to achieve 84.28% approximately using our band reduction method which is 2.36% increase compared to PCA (81.92%), 1.43% compared to the SDA (82.85%), and 7.61% compared to the original data set (76.67%). Introducing the mixed vegetation classes raised the overall accuracy even higher (85.79%).