We explored the effect of thrombin on human aortic smooth muscle cells (HASMCs) and further analyzed its role in the pathogenesis of atherosclerosis (AS). Thrombin-induced differentially expressed ...genes (DEGs) in HASMCs were identified by analyzing expression profiles from the GEO. Subsequently, enrichment analysis, GSEA, PPI network, and gene-microRNAs networks were interrogated to identify hub genes and associated pathways. Enrichment analysis results indicated that thrombin causes HASMCs to secrete various pro-inflammatory cytokines and chemokines, exacerbating local inflammatory response in AS. Moreover, we identified 9 HUB genes in the PPI network, which are closely related to the inflammatory response and the promotion of the cell cycle. Additionally, we found that thrombin inhibits lipid metabolism and autophagy of HASMCs, potentially contributing to smooth muscle-derived foam cell formation. Our study deepens a mechanistic understanding of the effect of thrombin on HASMCs and provides new insight into treating AS.
We demonstrate for the first time ZrO 2 ferroelectric field-effect transistors (FeFETs) for embedded non-volatile memory applications. Multiple sweeps of polarization versus voltage measurement ...demonstrate that a metal/ZrO 2 /Ge capacitor is entirely free of wake-up effect and has significantly improved fatigue characteristics compared to a HfZrO x control device. Thanks to relatively small remnant polarization and a high-quality ZrO 2 /Ge interface, up to 10 7 cycles program/erase endurance, 10 ns program/erase speed, and >10-year data retention at 85 °C are achieved.
In this paper, we use an automated tool flow in a 14 nm CMOS fin-shaped field-effect transistor (FinFET)/ static random access memory (SRAM) simulation-based design-technology cooptimization (DTCO) ...including both process-induced and intrinsic statistical variabilities. A 22 nm FinFET CMOS technology is used to illustrate the sensitivity to process-induced fin shape variation and to motivate this paper. Predictive Technology Computer Aided Design (TCAD) simulations have been carried out to evaluate the transistor performance ahead of silicon. Draft-diffusion simulations calibrated to the ensemble Monte Carlo simulation results are used to explore the process and the statistical variability space. This has been enabled by the automation of the tool flow and the dataset handling. The interplay between the process and the statistical variability has been examined in details. A two-stage compact model strategy is used to capture the interplay between process and statistical variability. To close the DTCO loop, the static noise margin and write noise margin sensitivity to cell design parameters and variability in FinFET-based SRAM designs are studied in details.
Recently, COVID-19 caused by the novel coronavirus SARS-CoV-2 has brought great challenges to the world. More and more studies have shown that patients with severe COVID-19 may suffer from cytokine ...storm syndrome; however, there are few studies on its pathogenesis. Here we demonstrated that SARS-CoV-2 coding protein open reading frame 8 (ORF8) acted as a contributing factor to cytokine storm during COVID-19 infection. ORF8 could activate IL-17 signaling pathway and promote the expression of pro-inflammatory factors. Moreover, we demonstrated that treatment of IL17RA antibody protected mice from ORF8-induced inflammation. Our findings are helpful to understand the pathogenesis of cytokine storm caused by SARS-CoV-2 and provide a potential target for the development of COVID-19 therapeutic drugs.
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•SARS-CoV-2 ORF8 activates IL-17 signaling pathway by interacting with host IL17RA•Treatment of IL17RA antibody protects mice from ORF8-induced inflammation
Biological Sciences; Microbiology; Virology
Abstract
Secukinumab is a specific neutralizing antibody for IL-17A. At present, numerous studies have confirmed the important role of IL-17A in sepsis, but the role of secukinumab in sepsis has not ...been studied. The present study explored the protective effect and underlying mechanism of secukinumab in severe sepsis model rats. We established a severe sepsis rat model using cecal ligation and puncture (CLP). The optimal dose of secukinumab was determined by observing the 7-day survival rate of severe sepsis model rats. The expression levels of TNF-α, IL-6, and IL-17A in plasma and lung tissue were determined by enzyme-linked immunosorbent assay. The degree of pathological damage to lung tissue was evaluated by hematoxylin–eosin (H–E) staining and pathological damage scale. The expressions of IKBα/NFκB pathway proteins and downstream-related inflammatory factors were detected by western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). Our results show that high-dose secukinumab can inhibit the activation of the IKBα/NFκB inflammatory pathway by neutralizing IL-17A and reducing the gene expression of pathway-related inflammatory cytokines, thereby reducing the levels of inflammatory cytokines in lung tissue and plasma, thereby reducing the damage of lung tissue in severe sepsis model rats and improving the systemic inflammatory response.
Acute lung injury is a major cause of death in sepsis. Tofacitinib (TOFA), a JAK inhibitor, has anti-inflammatory activity in autoimmune diseases, but its role in acute lung injury in sepsis remains ...unclear. The purpose of this study is to establish a septic rat model by cecal ligation and perforation, and to evaluate the effect of tofacitinib on the survival rate of septic rat model and its role in acute lung injury in septic rats and the possible mechanism of action. In this study, TOFA (1 mg/kg, 3 mg/kg, 10 mg/kg) was used to observe the survival rate of septic rats. It was found that TOFA (10 mg/kg) significantly improved the survival rate of septic rats. We selected TOFA (10 mg/kg) and focused on the protective effect of TOFA on acute lung injury. The results confirmed that TOFA significantly inhibited the expression of TNF-α, IL-1β, IL-6 and IFN-γ inflammatory factors, reduced the W/D weight ratio of septic lung tissue, and significantly improved lung histopathological damage. These results may be related to the inhibitory effect of TOFA on JAK-STAT/NF-κ B signaling pathway. In conclusion, for the first time, we found that TOFA has a protective effect against sepsis-induced acute lung injury, and it may be a promising drug for the treatment of acute lung injury in sepsis.
Pain catastrophizing in preoperative total knee arthroplasty (TKA) patients is associated with several poorly characterised factors in the literature. This study investigated the current state and ...associated factors of preoperative pain catastrophizing in patients undergoing TKA.
This descriptive cross-sectional study was conducted at the orthopedics ward of two tertiary hospitals in Lanzhou, China. Pain catastrophizing was measured using the Chinese versions of the Pain Catastrophizing Scale, Short Form-36 (physical function domain), Numerical Rating Scale, Oxford Knee Score, Hospital Anxiety and Depression Scale, and Life Orientation Test-Revised.
The study included 360 participants. Preoperative TKA pain catastrophizing in all patients was high, with a mean score of 24.92 (SD: 12.38). The stepwise multiple linear regression analysis revealed anxiety (β = 0.548, P < 0.01), education level (β = - 0.179, P < 0.01), physical function (β = - 0.156, P < 0.01), and pain intensity during activity (β = 0.105, P = 0.015) as associated factors for pain catastrophizing, possibly explaining 51.2% of the total variation (F = 95.149, P < 0.01).
Anxiety was the most relevant factor for pain catastrophizing in patients with preoperative TKA. Lower education levels, poor physical function, and stronger pain intensity during the activity were also associated with pain catastrophizing.
This paper presents a comprehensive full-scale three-dimensional simulation scaling study of the statistical threshold-voltage variability in bulk high- k /metal gate (HKMG) MOSFETs with gate lengths ...of 35, 25, 18, and 13 nm. Metal gate granularity (MGG) and corresponding workfunction-induced threshold-voltage variability have become important sources of statistical variability in bulk HKMG MOSFETs. It is found that the number of metal grains covering the gate plays an important role in determining the shape of the threshold-voltage distribution and the magnitude of the threshold-voltage variability in scaled devices in the presence of dominant variability sources (MGG, random discrete dopants, and line edge roughness). The placement of metal grains is found to also contribute to the total MGG variability. This paper presents the relative importance of MGG compared with other statistical variability sources. It is found that MGG can distort and even dominate the threshold-voltage statistical distribution when the metal grain size cannot be adequately controlled.
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The utilization of lighter alkanes into useful chemical products is essential for modern chemistry and reducing the CO2 emission. Particularly, n-butane has gained special attention ...across the globe due to the abundant production of maleic anhydride (MA). Vanadium phosphorous oxide (VPO) is the most effective catalyst for selective oxidation of n-butane to MA so far. Interestingly, the VPO complex exists in more or less fifteen different structures, each one having distinct phase composition and exclusive surface morphology and physiochemical properties such as valence state, lattice oxygen, acidity etc., which relies on precursor preparation method and the activation conditions of catalysts. The catalytic performance of VPO catalyst is improved by adding different promoters or co-catalyst such as various metals dopants, or either introducing template or structural-directing agents. Meanwhile, new preparation strategies such as electrospinning, ball milling, hydrothermal, barothermal, ultrasound, microwave irradiation, calcination, sol–gel method and solvothermal synthesis are also employed for introducing improvement in catalytic performance. Research in above-mentioned different aspects will be ascribed in current review in addition to summarizing overall catalysis activity and final yield. To analyze the performance of the catalytic precursor, the reaction mechanism and reaction kinetics both are discussed in this review to help clarify the key issues such as strong exothermic reaction, phosphorus supplement, water supplement, deactivation, and air/n-butane pretreatment etc. related to the various industrial applications of VPO.
In this paper, we present a FinFET-focused variability-aware compact model (CM) extraction and generation technology supporting design-technology co-optimization. The 14-nm CMOS technology generation ...silicon on insulator FinFETs are used as testbed transistors to illustrate our approach. The TCAD simulations include a long-range process-induced variability using a design of experiment approach and short-range purely statistical variability (mismatch). The CM extraction supports a hierarchical CM approach, including nominal CM extraction, response surface CM extraction, and statistical CM extraction. The accurate CM generation technology captures the often non-Gaussian distributions of the key transistor figures of merit and their correlations preserving also the correlations between process and statistical variability. The use of the hierarchical CM is illustrated in the simulation of FinFET-based SRAM cells and ring oscillators.
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