Search

Obesity is a complex metabolic disorder, manifesting as excessive accumulation of body fat. Ten-Eleven Translocation-2 (TET2) has garnered significant attention in the context of obesity due to its crucial role in epigenetic regulation and metabolic homeostasis. In this study, we aimed to investigate the effect of endothelial TET2 on obesity and explore the potential mechanism. We generated endothelial cell-specific TET2 deficiency mice and investigated endothelial TET2 using transcriptomic and epigenomic analyses. We determined the downregulation of endothelial TET2 in white adipose tissues. Furthermore, we identified that endothelial TET2 loss aggravated high-fat diet-induced obesity by inhibiting vascularization and thus suppressing white adipose tissue browning. Mechanistically, endothelial TET2 modulates obesity by engaging in endothelial fatty acid oxidation and angiocrine-mediated secretion of bone morphogenetic protein 4 (BMP4), in which nuclear factor-erythroid 2-related factor 2 (NRF2) serves as a key mediator. Our study reveals that endothelial TET2 regulates white adipose tissue browning by interacting with NRF2 to facilitate fatty acid oxidation and lipolysis in adipocytes.

Compared with other methods, the synthesis of metal nanoparticles by metal ion reduction using plant extracts as raw materials has the advantages of low cost, simple synthesis and environmental friendliness, and has garnered significant attention. To achieve this effect, in the form of green synthetic nano silver (AgNP), we mixed AgNO3 with attapulgite (ATP) and stirred it with clove plant extract at 80 °C. By changing the dosage of clove extract, a series of new samples were prepared by the same method. The shape and size of the synthesized silver nanoparticles on catalysts were visualized by transmission electron microscope (TEM) observations. The particle size of the optimally prepared nanoparticles ranges from 1 to 9 nm with spherical or roughly spherical forms. The inductively coupled plasma (ICP) results further demonstrated the reducing effect of clove extract on Ag. Increasing the amount of clove extract could promote the formation and loading of Ag on ATP. An outstanding catalytic performance of Ag/ATP under HCHO outperformed that synthesized without clove extract. With the addition of clove extract, the catalytic performance was enhanced by more than 40% compared to no addition. Among different nanoparticles, the catalytic oxidation activity of HCHO was best when the volume ratio of clove extract to Ag was 10:1. Therefore, the green synthesis of Ag/ATP catalysts using clove extracts can be considered an environmentally benign, superior approach.

Experiments have proven tool tilting in friction stir welding (FSW) can effectively suppress the formation of void defects. However, the mechanism of tool tilting on suppressing the formation of void defects has not been revealed. In this study, a CFD model considering the influence of tool tilting is established. A non-uniform distribution of normal pressure at the tool-workpiece contact interfaces is proposed to relate to the tool tilt angle. The discrete particle tracing method is used to characterize the formation of void defects in FSW. The heat generation, temperature distribution and plastic flow behaviors between the case without (i.e. 0° tool tilt angle) and with (i.e. 2.5° tool tilt angle) tool tilting are quantitatively compared and analyzed. The results show the tool tilting in FSW leads to higher heat flux and temperature near the pin side in the middle and low parts of the workpiece. Moreover, the frictional shear stress at the pin side/workpiece contact interface significantly increases when the tool is tilting, leading to a higher driving force for the plastic material to flow. As a result, the material flows farther to the advancing side of the workpiece after bypassing the tool when the tool is tilting at 2.5°, which helps to heal the voids on the advancing side of the FSW joints. The higher temperature with higher frictional shear stress enhances the plastic material flow in the middle and low part of the joints when the tool is tilting, which is attributed to suppressing the void defects. The model is validated by experimental results.

The conversion level of carbon in the process of biomass char utilization determines the overall efficiency of subsequent utilization, while the conversion rate of biomass char depends to a certain extent on the physical and chemical structure of biomass. In order to explore the evolution of char structure during high-temperature rapid pyrolysis of rice husk, a high-temperature rapid pyrolysis system of rice husk was designed and built. Through the accurate control of the residence time and temperature of rice husk pyrolysis, the reaction process can be accurately controlled. The physical and chemical structure of rice husk char was characterized by scanning electron microscope, Raman spectroscopy, specific surface area analysis and Fourier transform infrared spectroscopy. The yield of rice husk char, the type and development of pores, the changes of chemical functional groups and carbon structure under different pyrolysis temperatures and residence times were studied. The results were analyzed to obtain the trends of yield, pore types and development, chemical functional groups, and carbon structure of rice husk char at different pyrolysis temperatures and residence times. When the pyrolysis temperature is 1 300 ℃ and residence time is 13 s, the maximum specific surface area of rice husk char is 141.17 m2/g, the pore size is mainly distributed between 2−10 nm, and the surface structure is obviously broken. With the increase of pyrolysis temperature and residence time, the chemical structure of rice husk char becomes more and more deoxidized. The long residence time drives the highly ordered char structure of rice husk char and the concentration of aromatic rings with six or more dense benzene rings in rice husk char increases. High temperature significantly damaged the C—O bond and —OH bond in rice husk char, resulting in the breaking of the branch chain and bridge bond, release of oxygen-containing functional groups and graphitization of the carbon skeleton. The surface carbon elements were mainly dominated by C—C/C—H, and the content of carbon increases from 63.86% at 900 ℃ to 68.27% at 1300 ℃ when the residence time is 5 s. However, the contents of C—H, C—O, C=O and COO— decreased to different degrees. The surface oxygen elements were mainly dominated by COO and COOH. As the pyrolysis temperature increased, the number of benzene rings in rice husk char gradually decreased, the average number of aromatic rings increased, the number of surface methylene groups decreased, and the carbon activity decreased. Summarizing the structural evolution law of rice husk char will provide a reference for optimizing pyrolysis conditions, improving pyrolysis efficiency and subsequent combustion and gasification utilization of rice husk char.

Understanding of the ultrasonic effect on the process variables has important significance for the process optimization in ultrasonic vibration enhanced friction stir lap welding (UVeFSLW) of dissimilar Mg/Al alloys. In this study, the dislocation strain energy in both grain interior and grain boundary is considered to improve the formula for determing threshold thermal stress, and the constitutive equation is modified and used to develop the model for Mg/Al UVeFSLW process. The influences of ultrasonic vibration on heat generation, temperature profile, material flow and intermixing are quantitatively analyzed. It is found that the ultrasonic vibration induced the flow stress reduction gets larger, and the interfacial heat generation and viscous dissipation heat generation in the shear layer drop, which results in lower temperature at the tool/workpiece interface, intensifier material flow and larger material intermixed region in Mg/Al UVeFSLW. The interface temperature between the tool/workpiece and the profile of thermo-mechanically affected zone are experimentally measured, and compared with the predicted ones. The results show that the calculation accuracy of the modified model is improved.

Abstract Background Ischemic diseases represent a major global health care burden. Angiogenesis is critical in recovery of blood flow and repair of injured tissue in ischemic diseases. Ten–eleven translocation protein 2 (TET2), a member of DNA demethylases, is involved in many pathological processes. However, the role of TET2 in angiogenesis is still unrevealed. Methods TET2 was screened out from three DNA demethylases involved in 5-hydroxylmethylcytosine (5-hmC) regulation, including TET1, TET2 and TET3. Knockdown by small interfering RNAs and overexpression by adenovirus were used to evaluate the role of TET2 on the function of endothelial cells. The blood flow recovery and density of capillary were analyzed in the endothelial cells-specific TET2-deficient mice. RNA sequencing was used to identify the TET2-mediated mechanisms under hypoxia. Co-immunoprecipitation (Co-IP), chromatin immunoprecipitation-qPCR (ChIP-qPCR) and glucosylated hydroxymethyl-sensitive-qPCR (GluMS-qPCR) were further performed to reveal the interaction of TET2 and STAT3. Results TET2 was significantly downregulated in endothelial cells under hypoxia and led to a global decrease of 5-hmC level. TET2 knockdown aggravated the hypoxia‐induced dysfunction of endothelial cells, while TET2 overexpression alleviated the hypoxia‐induced dysfunction. Meanwhile, the deficiency of TET2 in endothelial cells impaired blood flow recovery and the density of capillary in the mouse model of hindlimb ischemia. Mechanistically, RNA sequencing indicated that the STAT3 signaling pathway was significantly inhibited by TET2 knockdown. Additionally, Co-IP, ChIP-qPCR and GluMS-qPCR further illustrated that STAT3 recruited and physically interacted with TET2 to activate STAT3 target genes. As expected, the effects of TET2 overexpression were completely suppressed by STAT3 silencing in vitro. Conclusions Our study suggests that the deficiency of TET2 in endothelial cells impairs angiogenesis via suppression of the STAT3 signaling pathway. These findings give solid evidence for TET2 to be a therapeutic alternative for ischemic diseases. Graphical Abstract

Vascular smooth muscle cells (VSMCs) are known for their fate plasticity in atherosclerosis plaque progression. Here, Zhai et al. show that extracellular traps generated from CD68 + VSMCs adversely contribute to plaque progression and highlight their unexpected role in plaque stability by regulating the direction of VSMC trans-differentiation.

The lap configurations and pin lengths have important influences on the joint quality and performance in Al-to-Mg friction stir lap welding (FSLW). But how these two factors affect the thermo-mechanical process in Al-to-Mg FSLW remains unclear. In this study, a computational fluid dynamics model considering the effects of local liquation, tool adhesive layer, tool tilt angle and pin thread is developed to analyze the FSLW process of Al-to-Mg with sheet thickness 3 plus 3 mm. The numerical simulation results are experimentally verified by the measured interface temperature and thermal mechanical affected zone profile. For pin length 3.8 mm, the Al/Mg configuration results in higher temperature and stronger material flow, so that intermetallic compounds (IMCs) are easy to form and joint strength is poor. The Al–Mg mixed region in Mg/Al configuration is mainly from the pin bottom to the lap interface, while that in Al/Mg configuration extends from the pin bottom to the position close to the top surface on the advancing side. In Mg/Al configuration, when the pin length increases, the peak temperature increases, the high-temperature region around the tool obviously expands and the tool can drive more materials to flow, which results in a larger Al–Mg mixed region, and the IMCs are more likely to be generated.

Objectives: To determine the role of MYL4 regulation of lysosomal function and its disturbance in fibrotic atrial cardiomyopathy. Background: We have previously demonstrated that the atrial-specific essential light chain protein MYL4 is required for atrial contractile, electrical, and structural integrity. MYL4 mutation/dysfunction leads to atrial fibrosis, standstill, and dysrhythmia. However, the underlying pathogenic mechanisms remain unclear. Methods and results: Rats subjected to knock-in of a pathogenic MYL4 mutant (p.E11K) developed fibrotic atrial cardiomyopathy. Proteome analysis and single-cell RNA sequencing indicate enrichment of autophagy pathways in mutant-MYL4 atrial dysfunction. Immunofluorescence and electron microscopy revealed undegraded autophagic vesicles accumulated in MYL4p.E11K rat atrium. Next, we identified that dysfunctional MYL4 protein impairs autophagy flux in vitro and in vivo. Cardiac lysosome positioning and mobility were regulated by MYL4 in cardiomyocytes, which affected lysosomal acidification and maturation of lysosomal cathepsins. We then examined the effects of MYL4 overexpression via adenoviral gene-transfer on atrial cardiomyopathy induced by MYL4 mutation: MYL4 protein overexpression attenuated atrial structural remodeling and autophagy dysfunction. Conclusions: MYL4 regulates autophagic flux in atrial cardiomyocytes via lysosomal mobility. MYL4 overexpression attenuates MYL4 p.E11K induced fibrotic atrial cardiomyopathy, while correcting autophagy and lysosomal function. These results provide a molecular basis for MYL4-mutant induced fibrotic atrial cardiomyopathy and identify a potential biological-therapy approach for the treatment of atrial fibrosis.

Nano-ZnO has a large specific surface area, small particle size, and strong polarity and can be used as an additive to modify the base asphalt. In this paper, the compatibility mechanism between nano-ZnO modifier and asphalt is analyzed. Solubility parameters, interaction energNano-ZnO and mean square displacement of nano-ZnO in matrix asphalt were calculated at different temperatures to study the compatibility of the nano-ZnO modifier and the matrix asphalt. The radial distribution functions and radii of gyration of the asphalt’s four components under the action of the nano-ZnO additive were calculated to investigate the effect of nano-ZnO on the molecular structure of the asphalt. The results show that the best compatibility between nano-ZnO and matrix asphalt is observed at 150 °C, especially when the nano-ZnO particle size was 6 Å. The particle sizes of nano-ZnO have little effect on the temperature at which the nano-ZnO-modified asphalt achieved its highest structural stability. Around 150 °C, the nano-ZnO-modified asphalt system with different particle sizes exhibit the highest stability and best compatibility. The addition of nano-ZnO improves the compactness of the asphalt structure and makes the asphalt more stable.

Background: Serine proteinase inhibitor A3 (SERPINA3) has been discovered in the pathogenesis of many human diseases, but little is known about the role of SERPINA3 in coronary artery disease (CAD). Therefore, we aim to determine its relationship with CAD and its function in the pathogenesis of atherosclerosis.Methods: In total 86 patients with CAD and 64 patients with non-CAD were compared. The plasma SERPINA3 levels were measured using ELISA. Logistic regression analysis and receiver-operating characteristic (ROC) analysis were performed to illustrate the association between plasma SERPINA3 levels and CAD. In vitro, real-time PCR (RT-PCR) and immunofluorescence staining were used to determine the expression of SERPINA3 in atherosclerotic plaques and their component cells. Then rat aortic smooth muscle cells (RASMCs) were transfected with siRNA to knock down the expression of SERPINA3 and human umbilical vein endothelial cells (HUVECs) were stimulated by SERPINA3 protein. EdU assay and scratch assay were used for assessing the capability of proliferation and migration. The cell signaling pathway was evaluated by western blot and RT-PCR.Results: Patients with CAD [104.4(54.5–259.2) μg/mL] had higher levels of plasma SERPINA3 than non-CAD [65.3(47.5–137.3) μg/mL] (P = 0.004). After being fully adjusted, both log-transformed and tertiles of plasma SERPINA3 levels were significantly associated with CAD. While its diagnostic value was relatively low since the area under the ROC curve was 0.64 (95% CI: 0.55–0.73). Secreted SERPINA3 might increase the expression of inflammatory factors in HUVECs. Vascular smooth muscle cells had the highest SERPINA3 expression among the aorta compared to endothelial cells and inflammatory cells. The knockdown of SERPINA3 in RASMCs attenuated its proliferation and migration. The phosphorylated IκBα and its downstream pathway were inhibited when SERPINA3 was knocked down.Conclusions: Elevated plasma SERPINA3 levels were associated with CAD. SERPINA3 can increase inflammatory factors expression in HUVECs. It can regulate VSMCs proliferation, migration, and releasing of inflammatory factors through the NF-κB signaling pathway. Thus, SERPINA3 played a significant role in the pathogenesis of atherosclerosis.

Background. Low-grade chronic inflammation in dysfunctional adipose tissue links obesity with insulin resistance through the activation of tissue-infiltrating immune cells. Numerous studies have reported on the pathogenesis of insulin-resistance. However, few studies focused on genes from genomic database. In this study, we would like to explore the correlation of genes and immune cells infiltration in adipose tissue via comprehensive bioinformatics analyses and experimental validation in mice and human adipose tissue. Methods. Gene Expression Omnibus (GEO) datasets (GSE27951, GSE55200, and GSE26637) of insulin-resistant individuals or type 2 diabetes patients and normal controls were downloaded to get differently expressed genes (DEGs), and GO and KEGG pathway analyses were performed. Subsequently, we integrated DEGs from three datasets and constructed commonly expressed DEGs’ PPI net-works across datasets. Center regulating module of DEGs and hub genes were screened through MCODE and cytoHubba in Cytoscape. Three most significant hub genes were further analyzed by GSEA analysis. Moreover, we verified the predicted hub genes by performing RT qPCR analysis in animals and human samples. Besides, the relative fraction of 22 immune cell types in adipose tissue was detected by using the deconvolution algorithm of CIBERSORT (Cell Type Identification by Estimating Relative Subsets of RNA Transcripts). Furthermore, based on the significantly changed types of immune cells, we performed correlation analysis between hub genes and immune cells. And, we performed immunohistochemistry and immunofluorescence analysis to verify that the hub genes were associated with adipose tissue macrophages (ATM). Results. Thirty DEGs were commonly expressed across three datasets, most of which were upregulated. DEGs mainly participated in the process of multiple immune cells’ infiltration. In protein-protein interaction network, we identified CSF1R, C1QC, and TYROBP as hub genes. GSEA analysis suggested high expression of the three hub genes was correlated with immune cells functional pathway’s activation. Immune cell infiltration and correlation analysis revealed that there were significant positive correlations between TYROBP and M0 macrophages, CSF1R and M0 macrophages, Plasma cells, and CD8 T cells. Finally, hub genes were associated with ATMs infiltration by experimental verification. Conclusions. This article revealed that CSF1R, C1QC, and TYROBP were potential hub genes associated with immune cells’ infiltration and the function of proinflammation, especially adipose tissue macrophages, in the progression of obesity-induced diabetes or insulin-resistance.

The occurrence of multiple critical slip surfaces with equal importance in rehabilitating and reinforcing slopes has been frequently observed in geotechnical engineering practices. The simultaneous determination of these potential slip surfaces is, however, not trivial. This paper presents a methodology based on the smoothed particle hydrodynamics (SPH) approach, which can simultaneously determine multiple failure slip surfaces and the debris flow process without previous knowledge or trial-and-error processes, and this methodology is validated against a slope with the presence of multiple critical slip surfaces. The proposed methodology serves as an efficient and effective alternative approach to traditional approaches, which involve cumbersome treatments performed by engineers based on their subjective experiences. The multiple sources of failure slip surfaces in slope stability are equivalent to multiple sources of initiation of slope failure, and it is found that SPH can provide a direct and systematic tool for identifying multiple failure slip surfaces. However, some minor potential problems are also found with the use of the SPH method in actual applications.

Pyrolysis processes of typical biomass, such as corn stalk and birch chips, were investigated by thermogravimetric analysis (TGA). The apparent activation energy and pre-exponential factor were calculated with the adoption of the improved Coats-Redfern integral method, 46 types of common mechanism functions, and the least square and iterative methods. By applying basic parameters of biomass pyrolysis, a reaction rate constant, activation entropy and activation enthalpy, activation Gibbs free energy, and the steric-hindrance factor were all calculated. Results showed that biomass pyrolysis can be divided into two primary reaction zones (Event 3 and Event 4). Event 3 is focused by cellulose and hemicellulose. Event 4 is oriented by lignin and cellulose. The thermogravimetric curves of the two biomass types under carbon dioxide and nitrogen atmospheres were roughly similar. The reaction mechanism function is 1 - alpha. It is possible to use activation entropy to represent the pre-exponential factor and to use the steric hindrance factor to predict the reaction rate.

A scheme for using a two-stage cyclone gasifier for high-temperature rice husk pyrolysis and gasification to reduce the tar content in biogas is presented in this study. The two-stage cyclone gasifier consisted of an upper cyclone high-temperature pyrolysis chamber and a lower steam spray gasifier. The staging pyrolysis and gasification process used in this study can increase the carbon conversion efficiency and reduce tar content by increasing the pyrolysis temperature. This process uses part of the produced gas for combustion in an external burner to generate high-temperature (1600 °C) anaerobic flue gas and to provide heat for pyrolysis and gasification. This study simulates the isothermal gas phase and the gas-solid flow field for the upper cyclone chamber, as well as the gas-solid flow field, with steam (heat transfer between the steam and the gas is considered), for the entire gasifier by varying the structural and operational parameters. The optimal parameters for the cyclone gasifier for good mixing and lengthy residence (2.3 to 4.8 s) of the rice husk particles were found to be inlet angles of 20° and 30° with inlet velocities between 40 and 80 m/s.

Rice husk and sawdust were selected as the raw materials for a study of biomass char yield in the range of 600 to 900 °C. It was found that temperature was the primary factor affecting the biomass char yield. The yield of the rice husk and sawdust chars decreased significantly with increasing temperature. As the residence time increased, the biomass char yield decreased. The smaller the size of the biomass particles, the higher the char yield. When the temperature exceeded 800 °C, the difference in the char yield was only slight. Given this finding, the surface morphologies of rice husk, sawdust, and their respective chars were investigated under various conditions via scanning electron microscopy. The effects of temperature on the pore structures were investigated by the Accelerated Surface Area and Porosimetry System. There were more holes in the biomass char, and the specific surface area was increased significantly as the temperature increased. The specific surface areas of rice husk and sawdust chars prepared at 900 °C were 320 and 1140 m2/g, respectively.

BACKGROUND: Curcumin (CUR) and anthocyanins (ACN) are recommended due to their bioactivities. However, their nutritional values and health benefits are limited by their low oral bioavailability. The incorporation of bioactive substances into polysaccharide--protein composite nanoparticles is an effective way to enhance their bioavailability. Accordingly, this study explored the fabrication of bovine serum albumin (BSA)--fucoidan (FUC) hybrid nanoparticles using a two-step pH-driven method for the delivery of CUR and ACN. RESULTS: Under a 1:1 weight ratio of BSA to FUC, the point of zero charge moved from pH ~ 4.7 for BSA to around 2.5 for FUC-coated BSA, and the formation of BSA--FUC nanocomplex was pH-dependent by showing the maximum CUR emission wave-length shifting from 546 nm (CUR-loaded BSA--FUC at pH 4.7) and 544 nm (CUR/ACN-loaded BSA--FUC nanoparticles at pH 4.7) to 540 nm (CUR-loaded BSA-FUC at pH 6.0) and 539 nm (CUR/ACN-loaded BSA--FUC nanoparticles at pH 6.0). Elevated concentrations of NaCl from 0 to 2.5 mol L-1 caused particle size increase from about 250 to about 800 nm, but showing no effect on the encapsulation efficiency of CUR. The CUR and ACN entrapped, respectively, in the inner and outer regions of the BSA--FUC nanocomplex were released at different rates. After incubation for 10 h, more than 80% of ACN was released, while less than 25% of CUR diffused into the receiving medium, which fitted well to Logistic and Weibull models. [ABSTRACT FROM AUTHOR]

Model updating is the process of calibrating model parameters to improve the accuracy of numerical prediction. To improve the accuracy and efficiency of model updating, this paper proposes a model updating method based on Bayesian theory and improved objective function. A natural frequency damage index is proposed based on the Bayesian theory, which is calculated according to the established damage position function and the measured frequency data. The distribution of the index can determine the damage location and the number of updated parameters for model updating. An objective function with weight terms is proposed based on strain assurance criterion to describes the difference between the finite element model and the actual structure, and the weight term of the objective function is determined by the sensitivity coefficient. Examples show that the improved model updating method is more accurate and efficient. [ABSTRACT FROM AUTHOR]