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The phenolic aldehyde syringaldehyde (SA) has been shown to have an antihyperglycemic effect in diabetic rats due to increased glucose utilization and insulin sensitivity. To understand the direct effect of SA on the GLP-1 receptor, STZ-induced diabetic rats were used. The levels of pro-inflammatory cytokines, liver enzymes, and renal function were measured using specific ELISA kits. The mechanisms of SA effects were investigated using CHO-K1 cells, pancreatic Min-6 cells, and cardiomyocyte H9c2 cells. The results indicated that the antihyperglycemic effect of SA in diabetic rats was abolished by blocking the GLP-1 receptor with an antagonist. SA has a direct effect on the GLP-1 receptor when using CHO-K1 cells transfected with the exogenous GLP-1 receptor gene. In addition, SA stimulated insulin production in Min-6 cells by activating GLP-1 receptors. SA caused a dose-dependent rise in GLP-1 receptor mRNA levels in cardiac H9c2 cells. These in vitro results support the notion that SA has a direct effect on the GLP-1 receptor. Otherwise, SA inhibited the increase of pro-inflammatory cytokines, including interleukins and tumor TNF-α, in type 1 diabetic rats in a dose-dependent manner. Moreover, as with liraglutide, SA reduced plasma lipid profiles, including total cholesterol and triglyceride, in mixed diet-induced type 2 diabetic rats. Intriguingly, chronic treatment with SA (as with liraglutide) reversed the functions of both the liver and the kidney in these diabetic rats. SA displayed less efficiency in reducing body weight and food consumption compared to liraglutide. In conclusion, SA effectively activates GLP-1 receptors, resulting in a reduction in diabetic-related complications in rats. Therefore, it is beneficial to develop SA as a chemical agonist for clinical applications in the future.

Andrographolide (ADG) is contained in bitter plants, and its effects are widely thought to be associated with taste receptors. The current study used animal studies and cell lines to investigate the role of ADG in diabetic models. The Takeda G-protein-coupled receptor (TGR5) was directly influenced by ADG, and this boosted GLP-1 synthesis in CHO-K1 cells transfected with the TGR5 gene. However, this was not seen in TGR5-mutant cells. The human intestinal L-cell line NCI-H716 showed an increase in GLP-1 production in response to ADG. In NCI-H716 cells, the TGR5 inhibitor triamterene reduced the effects of ADG, including the rise in TGR5 mRNA levels that ADG caused. Additionally, as with the antihyperglycemic impact in type-1 diabetic rats, the increase in plasma-active GLP-1 level caused by ADG was enhanced by a DPP-4 inhibitor. The recovery of the hypoglycemic effect in diabetic rats and the increase in plasma GLP-1 caused by ADG were both suppressed by TGR5 blockers. As a result, after activating TGR5, ADG may boost GLP-1 synthesis in diabetic rats, enhancing glucose homeostasis. In Min-6 cells, a pancreatic cell line grown in culture, ADG-induced insulin secretion was also examined. Blocking GLP-1 receptors had little impact, suggesting that ADG directly affects TGR5 activity in Min-6 cells. A TGR5 mRNA level experiment in Min-6 cells further confirmed that TGR5 is activated by ADG. The current study revealed a novel finding suggesting that ADG may activate TGR5 in diabetic rats in a way that results in enhanced insulin and GLP-1 production, which may be helpful for future research and therapies.

In the final approach stage of rendezvous and docking of a spacecraft, the pose parameters of the target spacecraft need to meet docking or berthing capture conditions. Visible light visual measurement systems are increasingly employed in spacecraft ground tests to extract the geometric features of spacecraft to calculate and verify the accuracy of pose parameters. Most current feature-segmentation algorithms are unable to break through the scale transformation problem of spacecraft movement and the noise interference of multi-layer insulation materials in imaging. To overcome these challenges, we propose a novel feature segmentation algorithm based on the framework of deep convolutional neural networks. Firstly, a full convolution model of the encoding-decoding structure is constructed based on data for the ground test. A feature concatenation module is applied and combined with a network backbone to improve the segmentation performance. Then, a comprehensive loss function is presented and optimized by the pose characteristics of the spacecraft in the approach phase. Furthermore, a specific spacecraft simulation dataset to train and test our segmentation model is built through data augmentation. The experimental results verify that the proposed method achieves accurate segmentation of spacecraft of different scales, suppresses the interference caused by multilayer insulation material, and has strong robustness against motion ambiguity. The pixel accuracy of our proposed method reaches 96.5%, and the mean intersection over union is 93.0%.

When urban subway tunnels cross existing bridge pile foundations, having a pile foundation underpinning that ensures the safe operation of existing bridges while enabling the safe construction of subway tunnels is the focus of attention. This paper takes the running tunnel project from Huaguoyuan West Station to Huaguoyuan East Station of Rail Transit Line 3 in Guiyang City, Guizhou Province as the background. The reasonableness and feasibility of the passive underpinning construction scheme for the Guihuang Viaduct was studied. The construction plan includes the following steps: underpinning pile construction, foundation pit excavation, the concreting of the underpinning bearing platform, and existing pile truncation. In order to ensure the structural safety of the existing viaduct during the construction of the pile foundation underpinning, a 3D numerical model of the construction of pile foundation underpinning and the whole process of tunnel construction was established. The settlement calculation results of the foundation pit and bridge pier were compared and analyzed with the field monitoring data to verify the accuracy of the numerical model. Further detailed analysis of the settlement of the bridge deck, the deformation of the existing piles, the axial forces of the existing piles, and the forces on the underpinning bearing platform was carried out. The results show that the bridge superstructure load can be transferred to the underpinning bearing platform smoothly after the existing pile truncation construction. The removal of obstacle piles during tunnel excavation has a very limited impact on the superstructure of the bridge, proving the reasonableness and feasibility of the construction plan.

Diabetes is commonly treated with glucagon-like peptide-1 receptor (GLP-1R) agonists including liraglutide and others. However, liraglutide was found to raise plasma glucose levels in normal rats. The current study aims to determine how liraglutide causes this contentious condition in rats, both normal and diabetic. An adrenalectomy was performed to investigate the relationship between steroid hormone and liraglutide. To investigate the effect of central liraglutide infusion on blood glucose in rats, rats were intracerebroventricularly administrated with liraglutide with or without HPA axis inhibitors such as berberine and dexamethasone. The results showed that a single injection of liraglutide caused a temporary increase in blood glucose in healthy rats. Another GLP-1R agonist, Exendin-4 (Ex-4), increased blood sugar in a manner similar to that of liraglutide. The effects of liraglutide were also blocked by guanethidine pretreatment and vanished in normal rats with adrenalectomy. Additionally, central infusion of liraglutide via intracerebroventricular (icv) injection into normal rats also causes a temporary increase in blood glucose that was blocked by GLP-1R antagonists or the inhibitors such as berberine and dexamethasone. Similarly, central liraglutide treatment causes temporary increases in plasma glucose, adrenocorticotropic hormone (ACTH), and cortisol levels, which were reversed by inhibitors for the hypothalamic-pituitary-adrenal (HPA) axis. In normal rats, the temporary glucose-increasing effect of liraglutide was gradually eliminated during consecutive daily treatments, indicating tolerance formation. Additionally, liraglutide and Ex-4 cross-tolerance was also discovered in normal rats. Liraglutide was more effective in diabetic rats than in normal rats in activating GLP-1R gene expression in the isolated adrenal gland. Interestingly, the effect of liraglutide on glycemic control varied depending on whether the rats were diabetic or not. In normal rats, bolus injection of liraglutide, such as Ex-4, may stimulate the HPA axis, resulting in hyperglycemia. The cross-tolerance of liraglutide and Ex-4 provided a novel perspective on GLP-1R activation.

Adipose-derived cytokines may contribute to the inflammation that occurs in metabolic syndrome (MetS). The Takeda G protein-coupled receptor (TGR5) regulates energy expenditure and affects the production of pro-inflammatory biomarkers in metabolic diseases. Etanercept, which acts as a tumor necrosis factor (TNF)-α antagonist, can also block the inflammatory response. Therefore, the interaction between TNF-α and TGR5 expression was investigated in rats with high-fat diet (HFD)-induced obesity. Heart tissues isolated from the HFD-induced MetS rats were analyzed. Changes in TGR5 expression were investigated with lithocholic acid (LCA) as the agonist. Betulinic acid (BA) was used to activate TGR5 in urinary bladders. LCA was more effective in the heart tissues of HFD-fed rats, although etanercept alleviated the function of LCA. STAT3 activation and higher TGR5 expression were observed in the heart tissues collected from HFD-fed rats. Thus, cardiac TGR5 expression is promoted by HFD through STAT3 activation in rats. Moreover, the urinary bladders of female rats fed a HFD showed a low response, which was reversed by etanercept. Relaxation by BA in the bladders was more marked in HFD-fed rats. The high TGR5 expression in HFD-fed rats was characterized using a mRNA assay, and the increased cAMP levels were found to be stimulated by BA in the isolated bladders. Therefore, TGR5 expression increases with a HFD in both the hearts and urinary bladders. Collectively, cytokine-medicated TGR5 activation was observed in the hearts and urinary bladders of rats.

Diet-induced obesity (DIO) is considered the main risk factor for cardiovascular diseases. Increases in the plasma levels of tumor necrosis factor alpha (TNF-α) is associated with DIO. Etanercept, a TNF-α inhibitor, has been shown to alleviate cardiac hypertrophy. To investigate the effect of etanercept on cardiac fibrosis in DIO model, rats on high fat diet (HFD) were subdivided into two groups: the etanercept group and vehicle group. Cardiac injury was identified by classic methods, while fibrosis was characterized by histological analysis of the hearts. Etanercept treatment at 0.8 mg/kg/week twice weekly by subcutaneous injection effectively alleviates the cardiac fibrosis in HFD-fed rats. STAT3 activation seems to be induced in parallel with fibrosis-related gene expression in the hearts of HFD-fed rats. Decreased STAT3 activation plays a role in the etanercept-treated animals. Moreover, fibrosis-related genes are activated by palmitate in parallel with STAT3 activation in H9c2 cells. Etanercept may inhibit the effects of palmitate, but it is less effective than a direct inhibitor of STAT3. Direct inhibition of STAT3 activation by etanercept seems unlikely. Etanercept has the ability to ameliorate cardiac fibrosis through reduction of STAT3 activation after the inhibition of TNF-α and/or its receptor.

Imperatorin, a dietary furocoumarin, is found not only in medicinal plants, but also in popular culinary herbs, such as parsley and fennel. Recently, imperatorin has been shown to activate GPR119 in cells. Another GPR, GPR131, also called TGR5 or G-protein-coupled bile acid receptor 1 (GPBAR1), is known to regulate glucose metabolism. Additionally, TGR5 activation increases glucagon-like peptide (GLP-1) secretion to lower blood sugar levels in animals. Therefore, the present study aims to determine whether the effects of imperatorin on GLP-1 secretion are mediated by TGR5. First, we transfected cultured Chinese hamster ovary cells (CHO-K1 cells) with the TGR5 gene. Glucose uptake was confirmed in the transfected cells using a fluorescent indicator. Moreover, NCI-H716 cells, which secrete GLP-1, were used to investigate the changes in calcium concentrations and GLP-1 levels. In addition, streptozotocin (STZ)-induced type 1-like diabetic rats were used to identify the effects of imperatorin in vivo. Imperatorin dose-dependently increased glucose uptake in CHO-K1 cells expressing TGR5. In STZ diabetic rats, similar to the results in NCI-H716 cells, imperatorin induced a marked increase of GLP-1 secretion that was reduced, but not totally abolished, by a dose of triamterene that inhibited TGR5. Moreover, increases in GLP-1 secretion induced by imperatorin and GPR119 activation were shown in NCI-H716 cells. We demonstrated that imperatorin induced GLP-1 secretion via activating TGR5 and GPR119. Therefore, imperatorin shall be considered as a TGR5 and GPR119 agonist.

The ethylene-regulated hypocotyl elongation of Arabidopsis thaliana involves many transcription factors. The specific role of MYC transcription factors in ethylene signal transduction is not completely understood. The results here revealed that two MYCs, MYC2 and MYC3, act as negative regulators in ethylene-suppressed hypocotyl elongation. Etiolated seedlings of the loss-of-function mutant of MYC2 or MYC3 were significantly longer than wild-type seedlings. Single- or double-null mutants of MYC2 and MYC3 displayed remarkably enhanced response to ACC(1-aminocyclopropane-1-carboxylate), the ethylene precursor, compared to wild-type seedlings. MYC2 and MYC3 directly bind to the promoter zone of ERF1, strongly suppressing its expression. Additionally, EIN3, a key component in ethylene signaling, interacts with MYC2 or MYC3 and significantly suppresses their binding to ERF1’s promoter. MYC2 and MYC3 play crucial roles in the ethylene-regulated expression of functional genes. The results revealed the novel role and functional mechanism of these transcription factors in ethylene signal transduction. The findings provide valuable information for deepening our understanding of their role in regulating plant growth and responding to stress.

The western plain of the Nansihu Lake Basin (NLB) is an important agricultural economic zone in Shandong Province, where there is a high content of fluoride in soils. Studying the content and influencing factors of fluoride in soils is of great significance for the maintenance of regional eco-logical security and human health. This study takes the farmland soils in the west of NLB as the research focus and uses a method based on GIS and geostatistics to quantitatively analyze the spatial variation characteristics of soil total fluoride and water-soluble fluoride contents to draw a map showing their spatial distribution. The effects on the spatial distribution of soil total fluoride and water-soluble fluoride were analyzed from the aspects of geomorphological type, soil parent material (stratigraphic lithology), crop type, and groundwater fluoride concentration, among others, and the correlation between groundwater and soil fluoride contents was also analyzed. Our study results in the following findings: (1) The average content of total fluoride in topsoil in the study area is 652.8 mg/kg, the national background value is exceeded in 99.5% of the sampling sites, and the background value of Shandong Province is exceeded in 98.7% of the sampling sites. The average water-soluble fluoride is 15.2 mg/kg and exceeds 5.0 mg/kg in 94.3% of the sampling sites. Topsoils have high values of total fluoride and water-soluble fluoride. (2) The total fluoride and water-soluble fluoride in topsoils exhibit moderate spatial variability, indicating that their spatial distribution is the result of structural factors such as soil parent materials and man-made random factors such as fluorinated fertilizers. (3) In the 2 m vertical profile of shallow soils, total fluoride and water-soluble fluoride increase with the increase in soil viscosity, and the water-soluble fluoride has the characteristics of surface aggregation due to the influence of soil adsorption. Because fluoride ions as ligands are easily adsorbed and form fluoride complexes with other ions such as aluminum ions, the water-soluble fluoride shows the characteristics of surface aggregation and fractionation. (4) The analysis of influencing factors reveals that the lithology of Quaternary strata, geomorpho-logical types, and planting crop types have significant effects on the distribution of the total fluoride and water-soluble fluoride in the topsoils, and the distribution of the groundwater soluble fluoride in the topsoils is not related to that in groundwater. Our study provides data and technical support for improving both the soil environmental quality and water quality of the eastern route of the South-to-North Water Transfer Project, thus helping to promote the sustainable development of the social economy and ecological environment in the NLB.

In this paper, the X-ray diffraction full width at half the maximum (XRD FWHM) of a 3.5 µm-thick hydride vapor phase epitaxy-aluminum nitride (HVPE-AlN) (002) face after high-temperature annealing was reduced to 129 arcsec. The tensile strain in the HVPE-AlN samples gradually released with the increasing annealing temperature. When the annealing temperature exceeded 1700 °C, an aluminum oxynitride (AlON) region was generated at the contact interface between HVPE-AlN and sapphire, and the AlON structure was observed to conform to the characteristics of Al5O6N by high-resolution transmission electron microscopy (HRTEM). A 265 nm light-emitting diode (LED) based on an HVPE-AlN template annealed at 1700 °C achieved a light output power (LOP) of 4.48 mW at 50 mA, which was approximately 57% greater than that of the original sample.