Search

Wilms' tumor (WT) is the most common pediatric renal malignancy. PDGFRβ belongs to the type III receptor tyrosine kinase family and is known to be involved in tumor metastasis and angiogenesis. Here, we studied the effect and underlying mechanism of PDGFRβ on WT G401 cells. Transwell assay and wound‐healing assay were used to detect the effect of PDGFRβ on G401 cells invasion and migration. Western blot and immunofluorescence were used to detect the expression of EMT‐related genes. The expression of PI3K/AKT/mTOR pathway proteins was detected by Western blot. The relationship between PDGFRβ and aerobic glycolysis was studied by assessing the expression of glycolysis‐related enzymes detected by qRT‐PCR and Western blot. The activity of HK, PK, and LDH was detected by corresponding enzyme activity kits. The concentration of lactic acid and glucose was detected by Lactic Acid Assay Kit and Glucose Assay Kit‐glucose oxidase method separately. To investigate the mechanism of PDGFRβ in the development of WT, the changes of glucose and lactic acid were analyzed after blocking PI3K pathway, aerobic glycolysis, or PDGFRβ. The key enzyme was screened by Western blot and glucose metabolism experiment after HK2, PKM2, and PDK1 were inhibited. The results showed that PDGFRβ promoted the EMT process by modulating aerobic glycolysis through PI3K/AKT/mTOR pathway in which PKM2 plays a key role. Therefore, our study of the mechanism of PDGFRβ in G401 cells provides a new target for the treatment of WT. [ABSTRACT FROM AUTHOR]

Osteosarcoma is a malignant tumor abundant in vascular tissue, and its rich blood supply may have a significant impact on its metabolic characteristics. PDGFRβ is a membrane receptor highly expressed in osteosarcoma cells and vascular wall cells, and its effect on osteosarcoma metabolism needs to be further studied. In this study, we discussed the effect and mechanism of action of PDGFRβ on glucose metabolism in human osteosarcoma (HOS) cells. GSEA, Pearson's correlation test, and PPI correlation analysis indicated positive regulation of PDGFRβ on aerobic glycolysis in osteosarcoma. The results of qPCR and western blot further confirmed the prediction of bioinformatics. Glucose metabolism experiments proved that PDGF/PDGFRβ could effectively promote aerobic glycolysis in osteosarcoma cells. In addition, the mitochondrial membrane potential (ΔΨm) experiment proved that the metabolic change triggered by PDGFRβ was not caused by mitochondrial damage. The PI3K pathway inhibitor LY294002, MEK pathway inhibitor U0126, or Warburg effect inhibitor DCA was used to perform western blot and glucose metabolism experiments, and the results showed that PDGFBB/PDGFRβ mainly activated the PI3K/AKT/mTOR/c-Myc pathway to promote aerobic glycolysis in osteosarcoma HOS cells. The newly elucidated role of PDGFRβ provides a novel metabolic therapeutic target for osteosarcoma. [ABSTRACT FROM AUTHOR]

High-fat diet (HFD) can cause obesity, inducing dysregulation of the visceral adipose tissue (VAT). This study aimed to explore potential biological pathways and hub genes involved in obese VAT, and for that, bioinformatic analysis of multiple datasets was performed. The expression profiles (GSE30247, GSE167311 and GSE79434) were downloaded from Gene Expression Omnibus. Overlapping differentially expressed genes (ODEGs) between normal diet and HFD groups in GSE30247 and GSE167311 were selected to run protein–protein interaction network, GO and KEGG analysis. The hub genes in ODEGs were screened by Cytoscape software and further verified in GSE79434 and obese mouse model. A total of 747 ODEGs (599 up-regulated and 148 down-regulated) were screened, and the GO and KEGG analysis showed that the up-regulated ODEGs were significantly enriched in inflammatory response and extracellular matrix receptor interaction pathways. On the other hand, the down-regulated ODEGs were involved in metabolic pathways; however, there were no significant KEGG pathways. Furthermore, six hub genes, Mki67, Rac2, Itgb2, Emr1, Tyrobp and Csf1r were acquired. These pathways and genes were verified in GSE79434 and VAT of obese mice. This study revealed that HFD induced VAT expansion, inflammation and fibrosis, and the hub genes could be used as therapeutic biomarkers in obesity. [ABSTRACT FROM AUTHOR]

Abstract The potential to improve the performance of molten salt solar power tower system (SPT) is explored through the proposal of CO 2 -based binary mixture cycle in the present study. The feasibility of using xenon and butane as the additives to the S-CO 2 cycle are discussed from the perspective of thermodynamic analysis. The detail parametric study is performed to reveal the effects of crucial parameters on the performance of 4 system configurations. Furthermore, the systematic comparison is conducted for 4 cycle layouts adopting CO 2 /xenon, CO 2 and CO 2 /butane separately to illustrate the mechanism of performance improvement of SPT system coupled to CO 2 -based binary mixture cycle. The optimal performance of the SPT system is also demonstrated. Finally, the best performance system layout and suitable additives are recommended. The results indicate the following issues. Adding xenon into S-CO 2 cycle can obviously improve the overall thermal efficiency and exergy efficiency. While the effects of butane as an additive are converse. The inter-cooling CO 2 /xenon cycle is recommended as the most suitable layout coupled to the SPT system, and the exergy efficiency is 1.18%∼1.32% higher than that of the SPT system with S-CO 2 inter-cooling cycle. Detail exergy loss fraction distribution illustrates that the receiver is the highest exergy loss part and followed by the heliostat field, and butane as an additive is beneficial to reduce the receiver exergy loss for its smaller temperature difference. The study can provide a novel way to improve the SPT system performance and give a clue to the addition of CO 2 -based binary mixture in power cycles particularly for the application of SPT system. Highlights • Improvement on SPT performance is explored via using CO 2 -based mixture cycle. • Effects of key parameters on SPT with various CO 2 -based mixture cycle are analyzed. • Systematic comparison of different system layouts is performed. • Optimal additive and cycle configuration are recommended for SPT. [ABSTRACT FROM AUTHOR]

Nephroblastoma is one of the most common renal malignancies in children, and tumor angiogenesis increases the risk of metastasis and recurrence. This study investigated the effect of the tumor microenvironment on angiogenesis in nephroblastoma cell and its molecular mechanism. The indirect co-culture model of human umbilical vein endothelial cells (HUVECs) was established using a conditioned medium from the nephroblastoma cell line G401. Cell medium was collected to prepare tumor-conditioned medium (TCM), which was applied to HUVECs. Western blotting and immunofluorescence assays were used to analyze the expression of tumor endothelial marker 8 (TEM8) and the elements phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB)/AKT signaling pathway at the protein level. In addition, the proliferation, invasion, migration, and tube formation of HUVECs after induction by TCM were analyzed by the Cell Counting Kit-8 (CCK-8), as well as by transwell invasion, wound-healing, and matrigel tube formation assays. Compared with that of the control group, the expression of TEM8, p-PI3K/PI3K, and p-AKT/AKT was increased, and proliferation, invasion, migration, and tubulogenesis were significantly enhanced in HUVECs induced by TCM. A PI3K pathway inhibitor (LY294002) weakened the canalization of HUVECs. These findings suggest that the nephroblastoma microenvironment can promote the transformation of endothelial cells (ECs) into tumor endothelial cells (TECs), significantly enhancing their proliferation, invasion, migration, and tubular formation, and this effect may be related to the PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • The evolution of S-CO 2 cycle is investigated. • S-CO 2 cycle's thermal, economic, and environmental benefits are concluded. • Recent research progress in demonstration projects is summarized. • Key issues and advice are stated from aspects of the S-CO 2 system and components. • S-CO 2 cycle provides a perspective to develop a good peak-shaving hybrid system. The potential contributions of this critical review are to provide a detailed complement of the status, barriers, and prospect of the supercritical carbon dioxide (S-CO 2) cycle power technology, and give a clue to promote its application. The state-of-the-art and existing problems of the S-CO 2 power technology are reviewed from the perspective of system analysis and component design. The emphasis is put on the application in next-generation high-temperature solar thermal power plants, next-generation compact nuclear reactor power plants, and coal-fired power plants to reveal the thermodynamic, economic, environmental, and flexible feasibility. The construction of the S-CO 2 demonstration power station developed in recent years is also summarized to provide a comprehensive understanding of the development route. Finally, the potential of the S-CO 2 cycle to establish a multi-generation system is proposed with a promising peak-shaving ability. Meanwhile, advice is stated to facilitate the further growth of this novel power conversion technology. This study is expected to help understand the recent development progress in S-CO 2 power technology. [ABSTRACT FROM AUTHOR]

Objective: Studies have found that high expression of human Kallistatin (HKS) in adipose tissue can improve obesity and its associated comorbidities, but the underlying mechanism of specific regulation is unclear. Methods: An obesity model was built by injecting 8-week-old C57BL/6 mice (n = 6 mice per group) with (Ad.Null and (Ad.HKS adenovirus into epididymal adipose tissue and fed with a high-fat diet (HFD). Insulin resistance-related proteins, AKT and IRS1, were detected in the liver, subcutaneous fat, and skeletal muscle by western blotting after one month of HFD. Epididymal adipose tissue was isolated after 24 h for culture, and exosomes were extracted by differential centrifugation. Enzyme-linked immunosorbent assay detected the expression of HKS protein in serum and exosomes. To examine the role of exosomes in AML12 insulin resistance, we used epididymal adipose tissue-derived exosomes or transfected (Ad.HKS into mature 3T3L1-derived exosomes to interfere with palmitic acid (PA)-induced mouse AML12 insulin resistance model. GW4869 was used to inhibit exosome biogenesis and release. Results: Our results showed that HFD-induced mice with high expression of HKS in epididymal adipose tissue had slower weight gain, lower serum triglycerides, reduced free fatty acids, and improved liver insulin resistance compared with the (Ad.Null group. We also demonstrated that HKS was enriched in epididymal adipose tissue-derived exosomes and released through the exosome pathway. In PA-induced AML12 cells, insulin resistance was alleviated after incubation of the HKS-related exosome; this effect was reversed with GW4869. Conclusion: High expression of HKS in epididymal adipose tissue could lead to its exocrine secretion in the form of exosomes and improve liver insulin resistance by promoting the phosphorylation of AKT. Production of high HKS vesicles might be a possible way to alleviate insulin resistance associated with obesity. [ABSTRACT FROM AUTHOR]

This case report discusses a female patient with axial spondyloarthritis (AS) who developed inflammatory bowel disease (IBD) after being treated with secukinumab (SEC), an interleukin-17 inhibitor. The patient had a family history of AS and psoriasis, and her symptoms worsened after starting SEC treatment. She experienced upper abdominal pain, nausea, vomiting, and gastrointestinal bleeding. The report highlights the association between SEC and the exacerbation of gastrointestinal symptoms leading to IBD. It also mentions the low incidence rate of IBD in patients treated with SEC and the lack of reports on neurological damage associated with SEC use. [Extracted from the article]

Coal tailings are complex materials of low value that discharged from a coal-cleaning plant. These types of solid waste own great application prospects, but so far their utilization is still rare. Water pollution is another noteworthy problem in the world today. Organic pollutants such as dyes must be removed from the water. In the face of increasingly serious problems of water pollution and coal tailings reuse, it is an innovative method to treat organic wastewater with materials prepared by coal tailings. In this work, a series of TiO 2 Nanotubes (TNTs) with Modified Coal Tailings (MCTs) prepared by different methods (including NaOH activation, H 2 SO 4 activation and calcination) were successfully synthesized by a hydrothermal method using MCTs and Tetrabutyl titanate as starting materials. The different influencing factors on the photocatalytic performance of TNT-MCTs composites were characterized through XRD, SEM, EDS, TEM, UV–vis DRS, FT-IR and BET surface measurements. The UV–vis DRS spectra revealed that the absorption edge of TNTs is 387 nm, while that of TNT-MCTs photocatalysts redshifts up to 393 nm. The photocatalytic activity of TNT-MCTs was evaluated by the photocatalytic depigmentation of methylene blue solution (MB, 10 mg/L) under UV light irradiation. The specific surface area, surface roughness and activity of MCTs were increased after loading with TNTs. The degradation rate of MB reached 91% in 60 min under UV light illumination. [Display omitted] [ABSTRACT FROM AUTHOR]

To investigate the seasonal variation of organophosphate esters (OPEs) in air particulate matter (PM) and the corresponding influence factors in indoor environment, 104 indoor PM samples were collected in a test home, Harbin, China, from March 2017 to March 2018. The Σ 12 OPEs concentrations ranged from 0.41 ng/m3 to 940 ng/m3. Tris(1-chloro-2-propyl) phosphate (TCIPP) was the most abundant OPE and accounted for 83.2% of the total OPEs. The Σ 12 OPEs concentrations in spring and summer were higher than those in autumn and winter. Outdoor total suspended particles (TSP) were the main factor that affected the concentration variation of OPEs in PM samples in the test home. Comparisons of the gas/particle (G/P) partitioning equilibrium models indicated that the Dachs-Eisenreich (D-E) model estimates were more reliable than the other models in this study. The particle fractions of OPEs with log K OA > 10.51 that predicted by all four models generally well matched the measured OPE particle fractions in the literatures. To OPEs with lower molecular weight, inhalation was the main exposure route and ingestion contributed mostly to OPEs with higher molecular weight. In addition, the estimated daily intakes (EDIs) and carcinogenic risks (CRs) posed by OPEs were all below the recommended values, indicating that the current OPE levels in the test home were within the safe thresholds. Unlabelled Image • The ∑ 12 OPEs concentrations in spring and summer were higher than those in autumn and winter. • Outdoor TSP was the main factor that affected the OPE concentration variation in PM samples. • The absorption mechanism dominates the G/P partitioning and the D-E model estimates were more reliable. • EDIs and CRs posed by OPEs via indoor air and dust were low, indicating a safe threshold. [ABSTRACT FROM AUTHOR]

• The energy-exergy-economic (3E) model is developed for S-CO 2 coal-fired system. • The layout of water-cooling wall is optimized for large scale S-CO 2 power plant. • The effect of inter-cooling process on performance of component is revealed. • Preliminarily conceptual design of the crucial components is proposed. The conceptual design and systematic comparison of S-CO 2 coal-fired power generation systems are performed in the viewpoint of the thermodynamic analysis and economic assessment to promote the practical application in the industry. First, the differences between the conventional steam boiler and S-CO 2 boiler are pointed out. 3 layouts of the water-cooling wall are compared in the aspect of the hydrodynamic characteristic and structural parameters to select the suitable one coupled to the S-CO 2 cycles. Based on the optimized water-cooling wall layout, the energy, exergy and economic analysis models of the integrated S-CO 2 coal-fired power systems are further developed. Finally, the mechanism of the inter-cooling thermodynamic process to improve the system performance is investigated and the distribution of the individual irreversibility is given. The systematic comparison is performed among 3 configurations of S-CO 2 coal-fired power plants with consideration of the thermo-economic performance. The conceptual design of key components is also provided. The results demonstrate that the S-CO 2 boiler is fatter due to 8 times larger mass flow rate of working fluid than the conventional steam boiler. The layout of water-cooling wall with the split flow strategy and vertical tubes is helpful in compacting the scale of the boiler for its less diameter and number of tubes, and its thermal efficiency is higher than that of other layouts. Among the 3 S-CO 2 cycle layouts studied, the S-CO 2 coal-fired power system with the inter-cooling cycle yields highest efficiency and is the most economic configuration. The thermal efficiency of the S-CO 2 coal-fired power plant composing the inter-cooling cycle is 47.69–49.09% with total thermal conductance of recuperators changed from 120 MW·K−1 to 180 MW·K−1 when the turbine inlet parameters are 620 °C/620 °C/30 MPa, and displays an advantage over the ultra-supercritical steam Rankine power plant. The system levelized cost of electricity is 0.0397 $·(kW·h)−1 and shows great commercial potential. The detailed discussion of this study is beneficial to a comprehensive understanding of various S-CO 2 coal-fired power systems and provide a clue to establish a practical power plant for the application of coal-fired industry. [ABSTRACT FROM AUTHOR]

• Effects of key parameters on performance of CO 2 -based mixture cycles are revealed. • Comprehensive performance evaluation method is proposed based on η exe, SPT - w -Δ T MH. • Trade-off relations for 3 performance metrics are found based on Pareto fronts. • Optimal cycle configuration, operating parameters and additive are recommended. This study provides an exploration on improving the performance of solar power tower (SPT) plant via integrating with the CO 2 -based mixture Brayton cycle, and proposes a comprehensive comparison method. The effects of the crucial parameters on the SPT system are firstly revealed. Then, a comprehensive evaluation method is proposed based on 3 performance metrics including exergy efficiency, specific work and temperature difference of the main-heater, which are used to assess the thermodynamic performance and the compatibility between the thermal storage system and power cycle. Finally, the trade-off relationships of these metrics are found. The optimal layout, additive and operating parameters are also pointed out based on the comparative results to meet different design requirements. The findings show that the effects of crucial parameters on the performance of SPT system are not monotonous and individual criterion cannot comprehensively evaluate the system performance. Using xenon as an additive can yield excellent performance with higher exergy efficiency and better compatibility between cycle and thermal storage system than the CO 2 alone. While the ability to generate specific work is decreased to 105–112 kW·kg−1 with xenon-added that compares to the inter-cooling S-CO 2 cycle (121–130 kW·kg−1). When the exergy efficiency is required higher than 33%, the inter-cooling CO 2 /xenon cycle is the primarily recommended layout for its large specific work and good compatibility between the thermal storage system and cycle. The findings provide a novel way to improve the efficiency of SPT system as well as the compatibility between the cycle and thermal storage system. [ABSTRACT FROM AUTHOR]

BACKGROUND: Coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) are the main treatment methods for left main artery disease (LMAD) and triple-vessel coronary artery disease (TVCAD). OBJECTIVE: This study aimed to evaluate the five-year post-treatment effects of CABG and PCI in patients with severe coronary vasculopathy. METHODS: A total of 430 patients with LMAD and/or triple-vessel coronary artery disease from November 2014 to July 2015 were enrolled retrospectively in the affiliated cardiovascular hospital of Shanxi Medical University and divided into the CABG group and PCI group. The living conditions of the patients were obtained through medical records and telephonic follow-ups five years after the surgery date. The independent risk factors for major adverse cardiovascular and cerebrovascular events (MACCE) were analyzed using logistic regression analysis. The effects of the two treatment methods were followed up and evaluated to measure the predictive ability of the Global Risk Classification (GRC) scoring system for MACCE after five years. RESULTS: There were 212 cases in the CABG group and 218 cases in the PCI group. Smoking (P = 0.047), diabetes (P = 0.031), LVEF (P = 0.020), LMAD (P = 0.008), and anterior descending branch lesions (P = 0.038) were significantly correlated with MACCE. The prevalence of MACCE in the CABG group and PCI group had no significant difference (P = 0.549). The GRC scoring system received an AUC of 0.701 for predicting MACCE. CONCLUSION: For patients with severe coronary artery disease, there was no significant difference in the prevalence of MACCE between the CABG and the PCI groups. Several independent risk factors for MACCE were found. The GRC scoring system showed a strong predictive ability for MACCE after five years of revascularization. [ABSTRACT FROM AUTHOR]

Adipose tissue remodeling is a dynamic process that is pathologically expedited in the obese state and is closely related to obesity-associated disease progression. This study aimed to explore the effects of human kallistatin (HKS) on adipose tissue remodeling and obesity-related metabolic disorders in mice fed with a high-fat diet (HFD). Adenovirus-mediated HKS cDNA (Ad.HKS) and a blank adenovirus (Ad.Null) were constructed and injected into the epididymal white adipose tissue (eWAT) of 8-weeks-old male C57B/L mice. The mice were fed normal or HFD for 28 days. The body weight and circulating lipids levels were assessed. Intraperitoneal glucose tolerance test (IGTT) and insulin tolerance test (ITT) were also performed. Oil-red O staining was used to assess the extent of lipid deposition in the liver. Immunohistochemistry and HE staining were used to measure HKS expression, adipose tissue morphology, and macrophage infiltration. Western blot and qRT-PCR were used to evaluate the expression of adipose function-related factors. At the end of the experiment, the expression of HKS in the serum and eWAT of the Ad.HKS group was higher than in the Ad.Null group. Furthermore, Ad.HKS mice had lower body weight and decreased serum and liver lipid levels after four weeks of HFD feeding. IGTT and ITT showed that HKS treatment maintained balanced glucose homeostasis. Additionally, inguinal white adipose tissue (iWAT) and eWAT in Ad.HKS mice had a higher number of smaller-size adipocytes and had less macrophage infiltration than Ad.Null group. HKS significantly increased the mRNA levels of adiponectin, vaspin, and eNOS. In contrast, HKS decreased RBP4 and TNFα levels in the adipose tissues. Western blot results showed that local injection of HKS significantly upregulated the protein expressions of SIRT1, p-AMPK, IRS1, p-AKT, and GLUT4 in eWAT. HKS injection in eWAT improves HFD-induced adipose tissue remodeling and function, thus significantly improving weight gain and dysregulation of glucose and lipid homeostasis in mice. • Gene therapy to explore the effect of human kallistatin (HKS) on metabolic disorders in obese mice. • HKS treatment improves HFD-induced weight gain, and glucose and lipid metabolism dysregulation in mice. • HKS may regulate adipose tissue remodeling and function to ameliorate metabolic disorders induced by HFD. [ABSTRACT FROM AUTHOR]

Meniere's disease (MD) represents one of the vertigo disorders characterized by triad symptoms (recurrent vertigo, fluctuating hearing loss, tinnitus or ear fullness). The diagnosis of MD relies on the accurate and detailed taking of medical history, and the differentiation between MD and vestibular migraine (VM) is of critical importance from the perspective of the treatment efficacy. VM is a highly prevalent vertigo condition and its typical symptoms (headache, vestibular symptoms, cochlear symptoms) mimic those of MD. Furthermore, the misdiagnosis in MD and VM could lead to VM patients mistakenly receiving the traumatic treatment protocol designed for MD, and sustaining unnecessary damage to the inner ear. Fortunately, thanks to the advances in examination technologies, the barriers to their differentiation are being gradually removed. These advances enhance the diagnostic accuracy of vertigo diseases, especially VM and MD. This review focused on the differentiation of VM and MD, with an attempt to synthesize existing data on the relevant battery of differentiation diagnosis (covering core symptoms, auxiliary tests [audiometry, vestibular tests, endolymphatic hydrops tests]) and longitudinal follow-up. Since the two illnesses are overlapped in all aspects, no single test is sufficiently specific on its own, however, patterns containing all or at least some features boost specificity. [ABSTRACT FROM AUTHOR]

Supercritical CO 2 (S-CO 2 ) Brayton cycles are recently proposed to be integrated into the solar power tower (SPT) due to their high efficiency and compactness. Comparison of different S-CO 2 Brayton cycle layouts is of great significance for selecting a suitable one in the SPT plant. Both of the efficiency and specific work are important performance criteria for the SPT plant. However, previous studies compared only one individual criterion, or both of them just separately. This paper puts forward a systematic comparison of different S-CO 2 Brayton cycle layouts based on multi-objective optimizations. The two performance criteria are compared simultaneously between different S-CO 2 cycle layouts by comparing the Pareto optimal fronts obtained from multi-objective optimizations. The results suggest that the inter-cooling cycle layout and the partial-cooling cycle layout can generally yield the most excellent performances, and followed by the recompression cycle layout and the pre-compression cycle layout, while the simple recuperation cycle layout has the worst performances. The advantages of the partial-cooling cycle layout and the inter-cooling cycle layout are more prominent compared with the other cycle layouts in the case of high compressor inlet temperature. The provided systematic comparison can be helpful in selecting the most suitable cycle layout for the application in SPT when there are specified requirements for the efficiency and the specific work. In addition, novel salts with high upper limit temperature (higher than 650 °C) are recommended to be developed as the heat transfer fluid for improving system performances. [ABSTRACT FROM AUTHOR]

Non‐alcoholic fatty liver disease (NAFLD) is a public health challenge and an increasing cause of chronic liver disease worldwide. However, the underlying molecular mechanism remains unclear. The aim of this study was to determine the precise role of serpina3c in the process of NAFLD. Male Apoe−/−/serpina3c−/− double knockout (DKO) and Apoe−/− mice were fed a high‐fat diet (HFD) for 12 weeks. Several markers of steatosis and inflammation were evaluated. In vitro cell models induced by palmitic acid (PA) treatment were used to evaluate the beneficial effect of serpina3c on necroptosis and the underlying molecular mechanism. Compared with Apoe−/− mice, DKO mice exhibited a significantly exacerbated hepatic steatosis, increased hepatic triglyceride content and expression of genes involved in lipid metabolism (SREBP1c and SCD1), promoted hepatic inflammation and fibrosis, promoted necroptosis by increasing expression of receptor‐interacting protein 3 (RIP3), phosphorylated mixed lineage kinase domain‐like (MLKL) and high mobility group box 1 (HMGB1). Notably, serpina3c deficiency increased β‐catenin, Foxo1, and Toll‐like receptor 4 (TLR4) protein expression. In vitro , serpina3c knockdown promoted necroptosis and lipid droplet formation under condition of lipotoxicity. However, these phenomena were reversed by the overexpression of serpina3c. Mechanistically, downregulation of serpina3c expression promoted Foxo1 and β‐catenin colocalized in the nucleus under condition of lipotoxicity, consequently upregulating the expression of TLR4. Conversely, disruption of Foxo1‐β/catenin by Foxo1 and β‐catenin inhibitors decreased TLR4 expression and ameliorated hepatic necroptosis in vitro. This study highlights a novel mechanism that serpina3c modulates NAFLD development by inhibiting necroptosis via β‐catenin/Foxo1/TLR4. [ABSTRACT FROM AUTHOR]

Abstract A comprehensive study of thermo-economic analysis and practical conceptual design of miniaturized lead-cooled fast reactor (LFR) composing supercritical CO 2 power cycle is proposed in order to promote the real application in the market. The thermodynamic model and economic model are established based on the following five supercritical CO 2 (S-CO 2) Brayton cycles integrating with the miniaturized LFR, separately. Moreover, the optimization algorithm is adopted to optimize the key parameters of five power cycles with the objectives of maximizing the system thermoelectric conversion efficiency and electricity production costs (EPC) simultaneously. The optimal cycle and optimum parameters are obtained for the integrated system. Furthermore, the structural parameters of key components are confirmed based on the above results. The main subsidiary systems are designed. Finally, the practical design of LFR composing S-CO 2 power cycle is carried out. The results shown that various parameters have different effects on the thermodynamic-economic performance of the system. The higher inlet temperature of turbine is beneficial to improve both thermodynamic and economic performance of the system. With the ƞ t,sys -EPC analyzed simultaneously, the recompression cycle is the optimal to operate with more working conditions. Its ƞ t,sys is from 36.68% to 44.46%, and EPC is from 0.050 $·kW−1·h−1 to 0.055 $·kW−1·h−1). [ABSTRACT FROM AUTHOR]

Fibrotic remodeling is an essential aspect of heart failure. Human kallistatin (KS, mouse Serpina3c homologs) inhibits fibrosis after myocardial infarction (MI) but the specific underlying mechanism is unknown. A total of 40 heart failure patients (HFPs) were enrolled and their plasma KS was measured using ELISA. Serpina3c−/− and C57BL/6 mice were used to construct the MI model. TGF-β1 or a hypoxic condition was established to interfere with the functioning of cardiac fibroblasts (CFs). RNA-seq was performed to assess the effect of Serpina3c on the transcriptome. The levels of KS were used as a predictor of readmission among the HFPs. Serpina3c expression decreased in MI hearts and CFs. Serpina3c−/− led to the aggravation of MI fibrosis, and increased the proliferation of CFs. The overexpression of Serpina3c in CFs had the opposite effect. Glycolysis-related genes were significantly increased in Serpina3c−/− group by RNA-seq. Enolase (ENO1), which is a key enzyme in glycolysis, increased most significantly. Inhibition of ENO1 could antagonize the promotion of Serpina3c−/− on the proliferation of CFs. Co-IP was performed to verify the interaction between Serpina3c and Nr4a1. Serpina3c−/− inhibited the acetylation of Nr4a1 and increased the degradation of Nr4a1. Activation of Nr4a1 could negatively regulate the expression of ENO1 and inhibited the proliferation of Serpina3c−/− CFs in Serpina3c−/− MI mice. Serpina3c inhibits the transcriptional activation of ENO1 by regulating the acetylation of Nr4a1, thereby reducing the fibrosis after MI by inhibiting glycolysis. Serpina3c is a potential target for prevention and treatment of heart failure after MI. [Display omitted] • KS/Serpina3c was down-regulated after MI. Knockout of Serpina3c led to aggravation of cardiac fibrosis. • KS/Serpina3c inhibited the excessive activation of glycolysis and the proliferation and differentiation of fibroblasts. • KS/Serpina3c inhibited the transcription of ENO1, a key enzyme of glycolysis, through Nr4a1 acetylation. [ABSTRACT FROM AUTHOR]

Serpina3 is a member of the serine protease inhibitor family and is involved in the inflammatory response. In this study, we investigated the effect of Serpina3c on pancreatic function in hypercholesterolemic mice. To investigate the role of Serpina3c in hyperlipidaemia, Serpina3c knockout mice were bred with Apoe-knockout mice (on a C57BL/6 background) to generate heterozygous Serpina3c-Apoe double knockout (Serpina3c+/−/Apoe+/−) mice and were then bred to obtain homozygotes. C57BL/6, Serpina3c−/−, Apoe−/−, and Apoe−/-Serpina3c−/− mice were fed normal chow, and Apoe−/− and Apoe−/-Serpina3c−/− mice were fed a high-fat diet (HFD). After feeding for 3 months, the mice were monitored for body weight, blood glucose, glucose tolerance, and insulin tolerance test (ITT). ELISA and immunohistochemistry were used to detect insulin levels and glucagon expression. Immunohistochemical staining for macrophages in the pancreas was also performed. Western blot analysis was performed on pancreatic tissues to detect the protein levels of insulin-associated molecules, the metalloproteinase MMP2, the tissue inhibitor TIMP2 and components of the JNK-related pathway. Blood glucose levels, glucose tolerance, and ITT were not significantly different among the groups. Serpina3c knockout resulted in blood lipid abnormalities in mice under HFD conditions. Insulin secretion was decreased in Apoe−/-Serpina3c−/− mice compared with Apoe−/− mice under normal chow conditions. In addition, Apoe−/-Serpina3c−/− mice exhibited increased insulin and glucagon secretion and expression after three months of HFD feeding, but insulin secretion was decreased in Apoe−/-Serpina3c−/− mice compared with Apoe−/− mice after the fifth month of HFD feeding. Serpina3c knockout increased MMP2 protein levels, whereas TIMP2 levels in the pancreas were decreased. Furthermore, Serpina3c knockout significantly upregulated the number of macrophages in the pancreas under HFD conditions. The JNK/AKT/FOXO1/PDX-1 axis was found to be involved in Serpina3c-regulated insulin secretion. These novel findings show that Serpina3c could play a protective role in insulin secretion partly through the JNK-related pathway under HFD conditions. • Serpina3c promotes insulin secretion and protects islet function in a high-fat environment. • Serpina3c mainly acts through JNK-related pathways. • Serpina3c knockout increases the inflammatory response in pancreas. [ABSTRACT FROM AUTHOR]

In this perspective paper, the present status and development tendency of concentrating solar power (CSP) are analyzed from two aspects: (1) Potential pathways to efficient CSP through improving operation temperature to above 700 °C; (2) Technologies for efficient solar collection, thermal storage, and power generation at >700 °C. Based on the analyses, barriers on the way to the high-temperature CSP are summarized. They are: (1) the lack of methodology for heliostat design and field layout optimization, (2) significant performance degradations of solar-thermal conversion, heat storage and transfer in receiver and thermal energy storage due to high temperature, (3) the lack of suitable supercritical CO 2 (S–CO 2) Brayton cycle for CSP and mature design methods for S–CO 2 components. To overcome these issues, perspectives on following three aspects are proposed. Firstly, optimization approaches for optimal heliostat size and layout, and game-changing techniques for heliostat structure design should be brainstormed. Secondly, receivers and thermal storage devices designed through efficiency-improving approaches and fabricated by durable materials should be developed to maintain efficient and reliable operation. Thirdly, the developments of novel S–CO 2 cycle and corresponding key components are eagerly desired to achieve efficient thermal-electric conversion. Perspectives from this paper would present possible approaches to efficient CSP. • Present status and perspectives of concentrating solar power are analyzed. • Approaches to optimal heliostat size, structure, and layout shall be brainstormed. • Efficient high-temperature receivers and heat storage devices shall be developed. • Developments of novel S–CO 2 cycle and its key components are eagerly desired. [ABSTRACT FROM AUTHOR]

We wished to investigate the role of a tilapia skin collagen polypeptide (TSCP; molecular weight <3 kDa) in alleviating liver and kidney injuries in aging mice induced by d -galactose (d -gal) and its underlying mechanism of action. First, we characterized TSCP. TSCP was passed through a 3-kDa ultrafiltration membrane, desalted in water by a solid-phase extraction column, purified further by reverse phase-high performance liquid chromatography, and analyzed by electrospray ionization mass spectrometry and tandem mass spectrometry. TSCP contained 17 types of amino acids (AAs) and 41 peptide chains of length 7 AAs to 22 AAs. The content of free AAs and total AAs of TSCP was 13.5% and 93.79%, respectively. Next, we undertook animal experiments. Mice were injected once-daily with D-gal (300 mg/kg body weight, s.c.) for 8 weeks, and TSCP was administered simultaneously once-daily by intragastric gavage. TSCP could visibly improve the decreased body weight, depressed appetite, and mental deterioration of mice triggered by d -gal. TSCP could also alleviate d -gal-induced damage to the liver and kidneys according to histopathology (especially high-dose TSCP). Consistent with these macroscopic and pathologic changes, TSCP could also prevent d -gal-induced increases in serum levels of alanine aminotransferase, aspartate transaminase, alkaline phosphatase, lipid peroxidation, creatinine and uric acid, as well as decreases in serum levels of immunoglobulin (Ig)G and IgM. Moreover, TSCP improved the activities of superoxide dismutase, catalase, and glutathione peroxidase, but also inhibited the increases in the levels of malondialdehyde and inducible nitric oxide synthase expression in the liver and kidneys of d -gal-treated mice. These results suggest that TSCP can alleviate the injuries to the liver and kidneys in aging mice induced by d -gal, and that its mechanism of action might be, at least partially, associated with attenuation of oxidative stress and enhancement of immune function. [ABSTRACT FROM AUTHOR]