Critical Roles of STAT3 in β-Adrenergic Functions in the Heart

BACKGROUND: β-Adrenergic receptors (βARs) play paradoxical roles in the heart. On one hand, βARs augment cardiac performance to fulfill the physiological demands, but on the other hand, prolonged activations of βARs exert deleterious effects that result in heart failure. The signal transducer and activator of transcription 3 (STAT3) plays a dynamic role in integrating multiple cytokine signaling pathways in a number of tissues. Altered activation of STAT3 has been observed in failing hearts in both human patients and animal models. Our objective is to determine the potential regulatory roles of STAT3 in cardiac βAR-mediated signaling and function. METHODS AND RESULTS: We observed that STAT3 can be directly activated in cardiomyocytes by β-adrenergic agonists. To follow up this finding, we analyzed βAR function in cardiomyocyte-restricted STAT3 knockouts and discovered that the conditional loss of STAT3 in cardiomyocytes markedly reduced the cardiac contractile response to acute βAR stimulation, and caused disengagement of calcium coupling and muscle contraction. Under chronic β-adrenergic stimulation, Stat3cKO hearts exhibited pronounced cardiomyocyte hypertrophy, cell death, and subsequent cardiac fibrosis. Biochemical and genetic data supported that Gαs and Src kinases are required for βAR-mediated activation of STAT3. Finally, we demonstrated that STAT3 transcriptionally regulates several key components of βAR pathway, including β1AR, protein kinase A, and T-type Ca(2+) channels. CONCLUSIONS: Our data demonstrate for the first time that STAT3 has a fundamental role in βAR signaling and functions in the heart. STAT3 serves as a critical transcriptional regulator for βAR-mediated cardiac stress adaption, pathological remodeling, and heart failure

Exergy Analysis of Phase-Change Heat-Storage Coupled Solar Heat Pump Heating System

With the rapid development of industrialization, the excessive use of fossil fuels has caused problems such as increased greenhouse gas emissions and energy shortages. The development and use of renewable energy has attracted increased attention. In recent years, solar heat pump heating technology that uses clean solar energy combined with high-efficiency heat pump units is the development direction of clean heating in winter in northern regions. However, the use of solar energy is intermittent and unstable. The low-valley electricity policy is a night-time electricity price policy. Heat pump heating has problems such as frosting and low efficiencies in cold northern regions. To solve these problems, an exergy analysis model of each component of a phase-change heat-storage coupled solar heat pump heating system was established. Exergy analysis was performed on each component of the system to determine the direction of optimization and improvement of the phase-change heat-storage coupled solar heat pump heating system. The results showed that optimizing the heating-end heat exchanger of the system can reduce the exergy loss of the system. When the phase-change heat-storage tank meets the heating demand, its volume should be reduced to lower the exergy loss of the tank heat dissipation. Air-type solar collectors can increase the income exergies of solar collectors

Nanoscale Refractive Index Sensors Based on Fano Resonance Phenomena

In this paper, a new refractive index sensor based on Fano resonance is introduced. It is mainly composed of two parts: a metal–insulator–metal as a base waveguide and an annular resonant cavity with a double notch and a double convex circle as a coupling structure. The sensing characteristics of the design are investigated via finite element calculations. The influence of the remaining structure parameters on the system’s sensing performance and the relationship between the wavelength corresponding to the Fano trough and the refractive index are also investigated. Furthermore, the structure is applied to refractive index sensors, resulting in a type with a sensitivity of 2740 nm/RIU and a figure of merit of 52.69

Nanoscale Refractive Index Sensors Based on Fano Resonance Phenomena

In this paper, a new refractive index sensor based on Fano resonance is introduced. It is mainly composed of two parts: a metal–insulator–metal as a base waveguide and an annular resonant cavity with a double notch and a double convex circle as a coupling structure. The sensing characteristics of the design are investigated via finite element calculations. The influence of the remaining structure parameters on the system’s sensing performance and the relationship between the wavelength corresponding to the Fano trough and the refractive index are also investigated. Furthermore, the structure is applied to refractive index sensors, resulting in a type with a sensitivity of 2740 nm/RIU and a figure of merit of 52.69

A Self-Rectifying Synaptic Memristor Array with Ultrahigh Weight Potentiation Linearity for a Self-Organizing-Map Neural Network

Two-terminal self-rectifying (SR)-synaptic memristors are preeminent candidates for high-density and efficient neuromorphic computing, especially for future three-dimensional integrated systems, which can self-suppress the sneak path current in crossbar arrays. However, SR-synaptic memristors face the critical challenges of nonlinear weight potentiation and steep depression, hindering their application in conventional artificial neural networks (ANNs). Here, a SR-synaptic memristor (Pt/NiOx/WO3–x:Ti/W) and cross-point array with sneak path current suppression features and ultrahigh-weight potentiation linearity up to 0.9997 are introduced. The image contrast enhancement and background filtering are demonstrated on the basis of the device array. Moreover, an unsupervised self-organizing map (SOM) neural network is first developed for orientation recognition with high recognition accuracy (0.98) and training efficiency and high resilience toward both noises and steep synaptic depression. These results solve the challenges of SR memristors in the conventional ANN, extending the possibilities of large-scale oxide SR-synaptic arrays for high-density, efficient, and accurate neuromorphic computing

Li-Ion Conduction and Stability of Perovskite Li_3/8Sr_7/16Hf_1/4Ta_3/4O₃

A solid Li-ion conductor with a high room temperature Li-ion conductivity and small interfacial resistance is required for its application in next-generation Li-ion batteries. Here, we prepared a cubic perovskite-related oxide with the general formula Li_3/8Sr_7/16Hf_1/4Ta_3/4O₃ (LSHT) by a conventional solid-state reaction method, which was studied by X-ray diffraction, electrochemical impedance spectroscopy, and ⁷Li MAS NMR. Li_3/8Sr_7/16Hf_1/4Ta_3/4O₃ has a high Li-ion conductivity of 3.8 × 10^–4 S cm^–1 at 25 °C and a low activation energy of 0.36 eV in the temperature range 298–430 K. It exhibits both high stability and small interfacial resistance with commercial organic liquid electrolytes, which makes it promising as a separator in Li-ion batteries

A novel anti-atherosclerotic mechanism of quercetin:Competitive binding to KEAP1 via Arg483 to inhibit macrophage pyroptosis

Natural antioxidants represented by quercetin have been documented to be effective against atherosclerosis. However, the related mechanisms remain largely unclear. In this study, we identified a novel anti-atherosclerotic mechanism of quercetin inhibiting macrophage pyroptosis by activating NRF2 through binding to the Arg483 site of KEAP1 competitively. In ApoE -/- mice fed with high fat diet, quercetin administration attenuated atherosclerosis progression by reducing oxidative stress level and suppressing macrophage pyroptosis. At the cellular level, quercetin suppressed THP-1 macrophage pyroptosis induced by ox-LDL, demonstrated by inhibiting NLRP3 inflammasome activation and reducing ROS level, while these effects were reversed by the specific NRF2 inhibitor (ML385). Mechanistically, quercetin promoted NRF2 to dissociate from KEAP1, enhanced NRF2 nuclear translocation as well as transcription of downstream antioxidant protein. Molecular docking results suggested that quercetin could bind with KEAP1 at Arg415 and Arg483. In order to verify the binding sites, KEAP1 mutated at Arg415 and Arg483 to Ser (R415S and R483S) was transfected into THP-1 macrophages, and the anti-pyroptotic effect of quercetin was abrogated by Arg483 mutation, but not Arg415 mutation. Furthermore, after administration of adeno associated viral vector (AAV) with AAV-KEAP1-R483S, the anti-atherosclerotic effects of quercetin were almost abolished in ApoE -/- mice. These findings proved quercetins suppressed macrophage pyroptosis by targeting KEAP1/NRF2 interaction, and provided reliable data on the underlying mechanism of natural antioxidants to protect against atherosclerosis. </p

Table_1_Effects of motor-cognitive interaction based on dual-task gait analysis recognition in middle age to aging people with normal cognition and mild cognitive impairment.docx

BackgroundMild cognitive impairment (MCI) is considered a transitional stage between cognitive normality and dementia among the elderly, and its associated risk of developing Alzheimer’s disease (AD) is 10–15 times higher than that of the general population. MCI is an important threshold for the prevention and control of AD, and intervention in the MCI stage may be the most effective strategy to delay the occurrence of AD.Materials and methodsIn this study, 68 subjects who met the inclusion criteria were divided into an MCI group (38 subjects) and normal elderly (NE) group (30 subjects). Both groups underwent clinical function assessments (cognitive function, walking function, and activities of daily living) and dual-task three-dimensional gait analysis (walking motor task and walking calculation task). Spatial-temporal parameters were obtained and reduced by principal component analysis, and the key biomechanical indexes were selected. The dual-task cost (DTC) was calculated for intra-group (task factor) and inter-group (group factor) comparisons.ResultsThe results of the principal component analysis showed that the cadence parameter had the highest weight in all three walking tasks. In addition, there were significant differences in the cadence both walking motor task (WMT) vs. walking task (WT) and walking calculation task (WCT) vs. WT in the MCI group. The cadence in the NE group only showed a significant difference between WMT and WT. The only differences between the MCI group and NE group was DTC cadence in WCT, and no differences were found for cadence in any of the three walking tasks.ConclusionThe results show that dual tasks based on cognitive-motor gait analysis of DTCcadence in MCI have potential value for application in early identification and provide theoretical support to improve the clinical diagnosis of MCI.</p