CD1d protects against hepatocyte apoptosis in non-alcoholic steatohepatitis.

BACKGROUND & AIMS: Hepatocyte apoptosis, a well-defined form of cell death in non-alcoholic steatohepatitis (NASH), is considered the primary cause of liver inflammation and fibrosis. However, the mechanisms underlying the regulation of hepatocyte apoptosis in NASH remain largely unclear. We explored the anti-apoptotic effect of hepatocyte CD1d in NASH. METHODS: Hepatocyte CD1d expression was analyzed in patients with NASH and mouse models. Hepatocyte-specific gene overexpression or knockdown and anti-CD1d crosslinking were used to investigate the anti-apoptotic effect of hepatocyte CD1d on lipotoxicity-, Fas-, and concanavalin (ConA)-mediated liver injuries. A high-fat diet, a methionine-choline-deficient diet, a Fas agonist, and ConA were used to induce lipotoxic and/or apoptotic liver injuries. Palmitic acid was used to mimic lipotoxicity-induced apoptosis in vitro. RESULTS: We identified a dramatic decrease in CD1d expression in hepatocytes of patients with NASH and mouse models. Hepatocyte-specific CD1d overexpression and knockdown experiments collectively demonstrated that hepatocyte CD1d protected against hepatocyte apoptosis and alleviated hepatic inflammation and injuries in NASH mice. Furthermore, decreased JAK2-STAT3 signaling was observed in NASH patient livers. Mechanistically, anti-CD1d crosslinking on hepatocytes induced tyrosine phosphorylation of the CD1d cytoplasmic tail, leading to the recruitment and phosphorylation of JAK2. Phosphorylated JAK2 activated STAT3 and subsequently reduced apoptosis in hepatocytes, which was associated with an increase in anti-apoptotic effectors (Bcl-xL and Mcl-1) and a decrease in pro-apoptotic effectors (cleaved-caspase 3/7). Moreover, anti-CD1d crosslinking effectively protected against Fas- or ConA-mediated hepatocyte apoptosis and liver injury in mice. CONCLUSIONS: Our study uncovered a previously unrecognized anti-apoptotic CD1d-JAK2-STAT3 axis in hepatocytes that conferred hepatoprotection and highlighted the potential of hepatocyte CD1d-directed therapy for liver injury and fibrosis in NASH, as well as in other liver diseases associated with hepatocyte apoptosis. IMPACT AND IMPLICATIONS: Excessive and/or sustained hepatocyte apoptosis is critical in driving liver inflammation and injury. The mechanisms underlying the regulation of hepatocyte apoptosis in non-alcoholic steatohepatitis (NASH) remain largely unclear. Here, we found that CD1d expression in hepatocytes substantially decreases and negatively correlates with the severity of liver injury in patients with NASH. We further revealed a previously unrecognized anti-apoptotic CD1d-JAK2-STAT3 signaling axis in hepatocytes, which confers significant protection against liver injury in NASH and acute liver diseases. Thus, hepatocyte CD1d-targeted therapy could be a promising strategy to manipulate liver injury in both NASH and other hepatocyte apoptosis-related liver diseases.

TGF-ß1 induces PD-1 expression in macrophages through SMAD3/STAT3 cooperative signaling in chronic inflammation.

Programmed cell death protein 1 (PD-1), a coinhibitory T cell checkpoint, is also expressed on macrophages in pathogen- or tumor-driven chronic inflammation. Increasing evidence underscores the importance of PD-1 on macrophages for dampening immune responses. However, the mechanism governing PD-1 expression in macrophages in chronic inflammation remains largely unknown. TGF-ß1 is abundant within chronic inflammatory microenvironments. Here, based on public databases, significantly positive correlations between PDCD1 and TGFB1 gene expression were observed in most human tumors. Of note, among immune infiltrates, macrophages as the predominant infiltrate expressed higher PDCD1 and TGFBR1/TGFBR2 genes. MC38 colon cancer and Schistosoma japonicum infection were used as experimental models for chronic inflammation. PD-1hi macrophages from chronic inflammatory tissues displayed an immunoregulatory pattern and expressed a higher level of TGF-ß receptors. Either TGF-ß1-neutralizing antibody administration or macrophage-specific Tgfbr1 knockdown largely reduced PD-1 expression on macrophages in animal models. We further demonstrated that TGF-ß1 directly induced PD-1 expression on macrophages. Mechanistically, TGF-ß1-induced PD-1 expression on macrophages was dependent on SMAD3 and STAT3, which formed a complex at the Pdcd1 promoter. Collectively, our study shows that macrophages adapt to chronic inflammation through TGF-ß1-triggered cooperative SMAD3/STAT3 signaling that induces PD-1 expression and modulates macrophage function.

Application, challenge and perspective of triboelectric nanogenerator as micro-nano energy and self-powered biosystem.

As a new type of energy harvesting technology, the triboelectric nanogenerator (TENG) can convert distributed energy into electrical energy. It is widely used in various fields such as wearable devices, biomedical devices, Internet of Things (IoT), natural environment, etc. However, there are still some issues that need to be solved for the commercial implementation of TENGs. This review focuses on four major kinds of applications for TENG as the platform of harvesting micro-nano energy: in vivo, in vitro, living environment and wild environment. The challenges and feasible techniques facing TENGs are summarized in three aspects, including low energy output, immature manufacturing technology and unreliable service life. We also review the recent progress in the strategies for improving the output performance and robustness of TENGs, including but not limited to material optimization, device engineering and power management. The aim is to establish a feasible framework of TENGs from laboratory to engineering application. Finally, the future trend of TENGs' application in distributed sensors and biomedical devices has prospected as a promising micro-nano energy for guiding the next innovation researches.

Large-Range Spurious Mode Elimination for Wideband SAW Filters on LiNbO3/SiO2/Si Platform by LiNbO3 Cut Angle Modulation.

A LiNbO3 (LN)/SiO2/Si multilayered structure was recently reported as a new platform for achieving wideband radio frequency (RF) filters. However, the in-band ripples in filters resulting from the spurious Rayleigh mode lead to deteriorated performance, and thus, a wide Rayleigh elimination window (REW) is highly desired for realizing spurious-free wideband surface acoustic wave (SAW) filters with a wide design space and good process tolerance. Here, we investigated the spurious mode suppression on the LN/SiO2/Si platform theoretically and experimentally through modulating the cut angle ( θ ) of LN. The K2 dispersion characteristics of the main mode (shear-horizontal wave) and spurious mode (Rayleigh wave) on LN/SiO2/Si substrates were systematically analyzed by the finite-element method (FEM), along with bulk LN for comparison. It is found that the REW is wider on LN/SiO2/Si than bulk LN, as Rayleigh wave can be totally eliminated with Cu electrode normalized thickness ( [Formula: see text]) ranging from 0.1 to 0.19 when θ is between 19° and 22° on the LN/SiO2/Si platform, in contrast to the quite narrow REW on bulk LN restricted to some specific [Formula: see text]. To verify the simulation results, resonators were prepared on 15°YX-LN/SiO2/Si, 20°YX-LN/SiO2/Si, bulk 15°YX-LN, and bulk 20°YX-LN. In addition, the typical spurious-free wideband SAW filter with [Formula: see text] nm based on the 20°YX-LN/SiO2/Si platform demonstrates high performance with a center frequency ( [Formula: see text]) of 1.27 GHz, a minimum insertion loss (ILmin) of 0.7 dB, and a 3-dB fractional bandwidth (FBW) of ~20.1%. This work provides a workable solution in fabricating spurious-free wideband and low-loss SAW filters for fifth-generation (5G) applications.

Bimetallic phosphide AlP/SiP2 composite as an anode material for lithium-ion batteries with long cycle life.

AlP and SiP2 are promising alloy-type anode materials for lithium-ion batteries (LIBs), owing to their good conductivity, high storage capacity and appropriate working potential. However, they still suffer from rapid capacity decay due to the huge volume expansion and the resultant pulverization. Carbon modification can not only relieve volume changes but also provide a conducting matrix for the active material. Moreover, the charge transfer of the multi-phase composite can be accelerated owing to its electric field at the heterointerface. Hence, a bimetallic phosphide AlP/SiP2@C composite was synthesized for the first time via a facile and scalable high energy ball milling method and applied as an anode material for LIBs. Benefitting from the above combined advantages of the heterostructure and carbon layer protection, the AlP/SiP2@C electrode delivered a high reversible capacity (1482 mA h g-1 at the current density of 0.3 A g-1) and durable lifespan (516 mA h g-1 after 4000 cycles at a current density of 3 A g-1), which are superior to those of the binary AlP@C and SiP2@C composites.

Combining multisurface model and Gouy-Chapman-Stern model to predict cadmium uptake by cabbage (Brassica Chinensis L.) in soils.

Cadmium is an extremely toxic substance known to cause serious health problems. The uptake of Cd in plants is critically affected by dissolved Cd in soil porewater, controlled by soil physicochemical properties. Rhizo-availability of Cd is assumed, as the Cd fraction is found on the plasma membrane of surface root cells. Based on the theory of Cd transformation in soil-crop systems, we established a novel combined mechanistic model related to soil, soil solutions, and crops. The combined model comprises a multisurface model (MSMs; solid adsorbent and porewater) and the Gouy-Chapman-Stern model (GCS; porewater and root surface). The results suggested that in mildly contaminated soil samples, optimum prediction was achieved when DTPA-extractable Cd was used as input variable (R2 = 0.723). Our approach was superior to single-step model calculation (MSMs: R2 = 0.613; GCS: R2 = 0.629) and prediction based on extractable soil Cd (R2 = 0.281). Introducing DTPA extraction expanded the range of model applications at different soil pHs. Our proposed mechanism model was based on soil physicochemical properties for Cd migration from soil to cabbage. Our model showed promise in predicting Cd bioavailability in soil with a wide pH range and evaluating soil risk near the standard Cd safety level.

The Simulation Design of Microwave Absorption Performance for the Multi-Layered Carbon-Based Nanocomposites Using Intelligent Optimization Algorithm.

The optimal design objectives of the microwave absorbing (MA) materials are high absorption, wide bandwidth, light weight and thin thickness. However, it is difficult for single-layer MA materials to meet all of these requirements. Constructing multi-layer structure absorbing coating is an important means to improve performance of MA materials. The carbon-based nanocomposites are excellent MA materials. In this paper, genetic algorithm (GA) and artificial bee colony algorithm (ABC) are used to optimize the design of multi-layer materials. We selected ten kinds of materials to construct the multi-layer absorbing material and optimize the performance. Two algorithms were applied to optimize the two-layer MA material with a total thickness of 3 mm, and it was found that the optimal bandwidth was 8.12 GHz and reflectivity was -53.4 dB. When three layers of MA material with the same thickness are optimized, the ultra-wide bandwidth was 10.6 GHz and ultra-high reflectivity was -84.86 dB. The bandwidth and reflectivity of the optimized material are better than the single-layer material without optimization. Comparing the GA and the ABC algorithm, the ABC algorithm can obtain the optimal solution in the shortest time and highest efficiency. At present, no such results have been reported.

Structure with thin SiOx/SiNx bilayer and Al electrodes for high-frequency, large-coupling, and low-cost surface acoustic wave devices.

With the development of fifth-generation wireless systems, the Internet of Things, and health services, surface acoustic wave (SAW)-based filters and sensors have attracted considerable interest. This study presents a new structure for high-frequency, large-coupling, and low-cost SAW devices that helps implement high-frequency and wideband filters and enhances the sensitivity of sensors. The structure is based on 15°Y-X LiNbO3, thin SiOx/SiNx bilayer overlay, and Al electrodes. Furthermore, a low-cost fabrication process for SAW devices based on this structure was designed. Simulation and experimental results show that the bilayer substantially weakens the leaky nature of shear-horizontal-type SAWs with a phase velocity higher than that of a slow-shear bulk wave in LiNbO3. Thus, the limitation related to the velocity of 4029 m/s was overcome, and the phase velocity reached approximately 4500 m/s, which means an increase of 50% compared with that of conventional Cu/15°Y-X LiNbO3 devices. Consequently, the frequency dramatically increases, and the quality of the SAW response is ensured. Simultaneously, a large electromechanical coupling factor close to 20% can be achieved, which is still suitable for wideband filters and sensors with high energy transduction coefficients. This new structure is expected to become a major candidate for SAW devices in the future.

Enhanced Performance of ZnO/SiO2/Al2O3 Surface Acoustic Wave Devices with Embedded Electrodes.

With the advent of the 5G era, surface acoustic wave (SAW) devices with a larger bandwidth and better temperature stability are strongly required, meanwhile the dimensions of devices are continuously scaling down. In this work, a new layout of ZnO/SiO2/Al2O3 SAW devices with embedded electrodes was developed, and with the help of the finite element method (FEM), the propagation characteristics were simulated. Through adopting embedded electrodes, a large electromechanical coupling coefficient (K2) of 6.6% for the Rayleigh mode can be achieved (5 times larger than that of the conventional ZnO/Al2O3 structure), feasible for wideband SAW devices, and a low acoustic velocity (Vp) of 2960 m/s is exhibited simultaneously, which benefits the miniaturization of SAW devices. The dramatic enhancement of K2 is mainly attributed to the more efficient excitation of SAW in piezoelectric films. Furthermore, a SiO2 overlay is added on the top of the structure to gain an excellent zero temperature coefficient of frequency (TCF). Experimentally, we successfully fabricated SAW one-port resonators based on the proposed structure and good characteristics of high K2, low Vp, and small TCF as simulated were confirmed. Our results show that the proposed structure provides a viable route to design SAW devices with a large bandwidth, small size, and robust temperature compensation for practical use.

Ultrafine FeNi3 Nanocrystals Embedded in 3D Honeycomb-Like Carbon Matrix for High-Performance Microwave Absorption.

The reasonable design of magnetic carbon-based composites is of great significance to improving the microwave absorption (MA) performance of the absorber. In this work, ultrafine FeNi3 nanocrystals (5-7 nm) embedded in a 3D honeycomb-like carbon matrix (FeNi3@C) were synthesized via a facile strategy that included a drying and carbonization process. Because of the soft magnetic property of the FeNi3 nanocrystals and their unique 3D honeycomb-like structure, the FeNi3@C composites exhibit excellent MA abilities. When the filler loading ratio of FeNi3@C/paraffin composites is only 30 wt%, the maximum reflection loss (RL) value is -40.6 dB at 10.04 GHz. Meanwhile, an ultra-wide absorption frequency bandwidth of 13.0 GHz (5.0-18.0 GHz over -10 dB) can be obtained in the thickness range of 2.0-4.5 mm, and this means that the absorber can consume 90% of the incident waves. It benefits from the dual loss components, multiple polarizations, and multiple reflections for improving MA performances of FeNi3@C composites. These observations suggest that the 3D honeycomb-like FeNi3@C composites have broad application prospects in exploring new MA materials that have a wide frequency bandwidth and strong absorption.