Fatty acylated caveolin-2 is a substrate of insulin receptor tyrosine kinase for insulin receptor substrate-1-directed signaling activation

AbstractHere, we demonstrate that insulin receptor (IR) tyrosine kinase catalyzes Tyr-19 and Tyr-27 phosphorylation of caveolin-2 (cav-2), leading to stimulation of signaling proteins downstream of IR, and that the catalysis is dependent on fatty acylation status of cav-2, promoting its interaction with IR. Cav-2 is myristoylated at Gly-2 and palmitoylated at Cys-109, Cys-122, and Cys-145. The fatty acylation deficient mutants are unable to localize in the plasma membrane and not phosphorylated by IR tyrosine kinase. IR interacts with the C-terminal domain of cav-2 containing the cysteines for palmitoylation. IR mutants, Y999F and K1057A, but not W1220S, fail interaction with cav-2. Insulin receptor substrate-1 (IRS-1) is recruited to interact with the IR-catalyzed phospho-tyrosine cav-2, which facilitates IRS-1 association with and activation by IR to initiate IRS-1-mediated downstream signaling. Cav-2 fatty acylation and tyrosine phosphorylation are necessary for the IRS-1-dependent PI3K-Akt and ERK activations responsible for glucose uptake and cell survival and proliferation. In conclusion, fatty acylated cav-2 is a new substrate of IR tyrosine kinase, and the fatty acylation and phosphorylation of cav-2 present novel mechanisms by which insulin signaling is activated

Interference-Compensating Magnetometer Calibration With Estimated Measurement Noise Covariance for Application to Small-Sized UAVs

This article proposes a new interference-compensating magnetometer calibration scheme aided by a gyroscope sensor, which could reduce the effect of induced magnetic interference due to nearby onboard current flow. By using the innovation process and a linear matrix inequality approach, mean and variance of the induced magnetic interference are estimated to ensure that their physical meaningful values are taken to be closest to the empirically measured ones. The values are reflected in the update step of the extended Kalman filter in order to accurately estimate the calibration parameters and the corresponding direction. Results of experiments performed using a real unmanned aerial vehicle (UAV) demonstrate that the proposed calibration scheme compensates well for the disturbing magnetic interference arising from the UAV's onboard current and hence reduces the estimation error of its yaw angle, or its heading direction, by approximately two-thirds of that obtained using the existing scheme.11Nsciescopu

Sparse Variational Deterministic Policy Gradient for Continuous Real Time Control

Recent advancements in deep reinforcement learning for real control tasks have received interest from many researchers and field engineers in a variety of industrial areas. However, in most cases, optimal policies obtained by deep reinforcement learning are difficult to implement on cost-effective and lightweight platforms such as mobile devices. This can be attributed to their computational complexity and excessive memory usage. For this reason, this study proposes an off-policy deep reinforcement learning algorithm called the sparse variational deterministic policy gradient (SVDPG). SVDPG provides highly efficient policy network compression under the standard reinforcement learning framework. The proposed SVDPG integrates Bayesian pruning, which is known as a state-of-the-art neural network compression technique, with the policy update in an actor-critic architecture for reinforcement learning. It is demonstrated that SVDPG achieves a high compression rate of policy networks for continuous control benchmark tasks while preserving a competitive performance. The superiority of SVDPG in low-computing power devices is proven by comparing the level of compression in terms of the memory requirements and computation time on a commercial microcontroller unit. Finally, it is confirmed that the proposed SVDPG is also reliable in real-world scenarios since it can be applied to the swing-up control of an inverted pendulum system.11Nsciescopu

Anti-Aging and Lightening Effects of Au-Decorated Zeolite-Based Biocompatible Nanocomposites in Epidermal Delivery Systems

The main challenges in developing zeolites as cosmetic drug delivery systems are their cytotoxicities and the formation of drug-loading pore structures. In this study, Au-decorated zeolite nanocomposites were synthesized as an epidermal delivery system. Thus, 50 nm-sized Au nanoparticles were successfully deposited on zeolite 13X (super cage (α) and sodalite (β) cage structures) using the Turkevich method. Various cosmetic drugs, such as niacinamide, sulforaphane, and adenosine, were loaded under in vitro and in vivo observations. The Au-decorated zeolite nanocomposites exhibited effective cosmetic drug-loading efficiencies of 3.5 to 22.5 wt% under various conditions. For in vitro cytotoxic observations, B16F10 cells were treated with various cosmetic drugs. Niacinamide, sulforaphane, and adenosine-loaded Au-decorated zeolite nanocomposites exhibited clear cell viability of over 80%. Wrinkle improvement and a reduction in melanin content on the skin surface were observed in vivo. The adenosine delivery system exhibited an enhanced wrinkle improvement of 203% compared to 0.04 wt% of the pure adenosine system. The niacinamide- and sulforaphane-loaded Au-decorated zeolite nanocomposites decreased the skin surface melanin content by 123% and 222%, respectively, compared to 2 and 0.01 wt% of pure niacinamide and sulforaphane systems, respectively. As a result, Au-decorated zeolite nanocomposites show great potential as cosmetic drug epidermal delivery systems for both anti-aging and lightening effects

Targeted Deletion of Thymosin Beta 4 in Hepatic Stellate Cells Ameliorates Liver Fibrosis in a Transgenic Mouse Model

Liver fibrosis is the most common feature of liver disease, and activated hepatic stellate cells (HSCs) are the main contributors to liver fibrosis. Thus, finding key targets that modulate HSC activation is important to prevent liver fibrosis. Previously, we showed that thymosin β4 (Tβ4) influenced HSC activation by interacting with the Hedgehog pathway in vitro. Herein, we generated Tβ4 conditional knockout (Tβ4-flox) mice to investigate in vivo functions of Tβ4 in liver fibrosis. To selectively delete Tβ4 in activated HSCs, double-transgenic (DTG) mice were generated by mating Tβ4-flox mice with α-smooth muscle actin (α-Sma)-Cre-ERT2 mice, and these mice were administered carbon tetrachloride (CCl4) or underwent bile duct ligation to induce liver fibrosis. Tβ4 was selectively suppressed in the activated HSCs of DTG mouse liver, and this reduction attenuated liver injury, including fibrosis, in both fibrotic models by repressing Hedgehog (Hh) signaling. In addition, the re-expression of Tβ4 by an adeno-associated virus reversed the effect of HSC-specific Tβ4 deletion and led to liver fibrosis with Hh activation in CCl4-exposed mice treated with tamoxifen. In conclusion, our results demonstrate that Tβ4 is a crucial regulator of HSC activation, suggesting it as a novel therapeutic target for curing liver fibrosis

The effects of decomposition of CpZr(NMe2)3 on atomic layer deposition for high-k ZrO2 thin films

In this study, the thermal stability of cyclopentadienyl tris(dimethylamino)zirconium (CpZr(NMe2)3), a representative precursor for the deposition of ZrO2 films, was evaluated after exposure to thermal stress. As a result, we predicted that dimethylamine, and trimethylamine may be generated when CpZr(NMe2)3 was heated. These impurities affect the growth of film and the properties of the film. In particular, by changing the vapor pressure of CpZr(NMe2)3, thin films with different characteristics are formed under the same process conditions, and consequently, the reliability of the device was also reduced. Therefore, this study demonstrates that the decomposition of precursors must be studied to develop new precursors and highly reliable thin films and devices. © 2022 The AuthorsTRU

Single-particle Mineralogy of Asbestos Mineral Particles by the Combined Use of Low-Z Particle EPMA and ATR-FTIR Imaging Techniques

Abstract In this work, two single particle analytical techniques such as a quantitative energy-dispersive electron probe X-ray microanalysis (ED-EPMA), called low-Z particle EPMA, and attenuated total reflectance Fourier transform-Infrared (ATR-FTIR) imaging were applied in combination for the characterization and distinction of six standard asbestos and one non-asbestos Mg-silicate minerals of micrometer size. Asbestos fibers have been reported as a natural carcinogen which causes some serious illness like mesothelioma, asbestosis, and lung cancer. Atmospheric aerosols are heterogeneous mixtures and airborne asbestos fibers would be present due to their extensive industrial uses for various purposes. The fibers could also be airborne from natural and anthropogenic sources. As different asbestos fibers have different carcinogenic properties, it is important to determine different types of individual asbestos and non-asbestos Mg-silicate mineral particles and their sources for the public health management. In our previous works, the speciation of individual aerosol particles was performed by the combined use of the two single-particle analytical techniques, which demonstrated that the combined use of the two analytical techniques is powerful for detailed characterization of externally heterogeneous aerosol particle samples and has great potential for characterization of atmospheric aerosols. In this work, it is demonstrated that the identification and differentiation of asbestiform and non-asbestiform Mg-silicate mineral particles is clearly performed using the two single particle analytical techniques in combination than using either technique individually. Especially, anthophyllite and talc can be differentiated using this analytical approach, which has not been easy up until now

Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models

Immunomodulation by radiotherapy (RT) is an emerging strategy for improving cancer immunotherapy. Nanomaterials have been employed as innovative tools for cancer therapy. This study aimed to investigate whether mesoporous silica nanoparticles (MSNs) enhance RT-mediated local tumor control and the abscopal effect by stimulating anti-cancer immunity. Hepa1-6 murine hepatocellular carcinoma syngeneic models and immunophenotyping with flow cytometry were used to evaluate the immune responses. When mice harboring bilateral tumors received 8 Gy of X-rays on a single tumor, the direct injection of MSNs into irradiated tumors enhanced the growth inhibition of irradiated and unirradiated contralateral tumors. MSNs enhanced RT-induced tumor infiltration of cytotoxic T cells on both sides and suppressed RT-enhanced infiltration of regulatory T cells. The administration of MSNs pre-incubated with irradiated cell-conditioned medium enhanced the anti-tumor effect of anti-PD1 compared to the as-synthesized MSNs. Intracellular uptake of MSNs activated JAWS II dendritic cells (DCs), which were consistently observed in DCs in tumor-draining lymph nodes (TDLNs). Our findings suggest that MSNs may capture tumor antigens released after RT, which is followed by DC maturation in TDLNs and infiltration of cytotoxic T cells in tumors, thereby leading to systemic tumor regression. Our results suggest that MSNs can be applied as an adjuvant for in situ cancer vaccines with RT

Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models

Immunomodulation by radiotherapy (RT) is an emerging strategy for improving cancer immunotherapy. Nanomaterials have been employed as innovative tools for cancer therapy. This study aimed to investigate whether mesoporous silica nanoparticles (MSNs) enhance RT-mediated local tumor control and the abscopal effect by stimulating anti-cancer immunity. Hepa1-6 murine hepatocellular carcinoma syngeneic models and immunophenotyping with flow cytometry were used to evaluate the immune responses. When mice harboring bilateral tumors received 8 Gy of X-rays on a single tumor, the direct injection of MSNs into irradiated tumors enhanced the growth inhibition of irradiated and unirradiated contralateral tumors. MSNs enhanced RT-induced tumor infiltration of cytotoxic T cells on both sides and suppressed RT-enhanced infiltration of regulatory T cells. The administration of MSNs pre-incubated with irradiated cell-conditioned medium enhanced the anti-tumor effect of anti-PD1 compared to the as-synthesized MSNs. Intracellular uptake of MSNs activated JAWS II dendritic cells (DCs), which were consistently observed in DCs in tumor-draining lymph nodes (TDLNs). Our findings suggest that MSNs may capture tumor antigens released after RT, which is followed by DC maturation in TDLNs and infiltration of cytotoxic T cells in tumors, thereby leading to systemic tumor regression. Our results suggest that MSNs can be applied as an adjuvant for in situ cancer vaccines with RT