Search

Establishing an accurate prediction model of pipeline corrosion depth is of great practical significance for effectively evaluating the service life of pipeline, which has the advantages of saving manpower and financial resources. Based on the basic theory of gray GM (1,1) model, the improved GM (1,1) models were established by using the method of background value optimization (improved model I), translation transformation (improved model II) and combination of background value optimization and translation transformation (improved model III), and the differences of prediction accuracy between the improved models and the traditional model were analyzed. The results show that the mean relative errors of improved models are lower than those of traditional model. When the coefficient C is 30, the mean relative errors of improved model II and improved model III are only 1.073% and 1.097%. The accuracy of each improved model is higher than that of the traditional model, and the accuracy of improved model III is generally high. With the increase of coefficient C, the prediction accuracy of improved model III and improved model II gradually increases, the reasonable selection of coefficient C is helpful to improve the accuracy of improved model II and improved model III. [ABSTRACT FROM AUTHOR]

Background: Trimethylamine N-oxide (TMAO)-related metabolites are associated with the pathogenesis of atherosclerotic cardiovascular disease (ASCVD) and are known to disrupt lipid metabolism. The aims of this study were to evaluate the associations between TMAO-related metabolites and blood lipids and determine how lowering the lipid profile via rosuvastatin therapy influences TMAO-related metabolites. Methods: A total of 112 patients with suspected ASCVD were enrolled in this study. The levels of plasma TMAO-related metabolites, including TMAO, choline, carnitine, betaine, and γ-butyrobetaine (GBB), were analyzed by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC/MS/MS) before and after rosuvastatin therapy in all patients. Statistical methods were used to detect the associations between TMAO-related metabolites and blood lipids and determine how rosuvastatin therapy alters the levels of these metabolites. Results: A significant positive correlation was found between TMAO and triglycerides (TG) (r = 0.303, P < 0.05). Furthermore, significant negative correlations were found between TMAO and high-density lipoprotein cholesterol (HDL-c) and between betaine and low-density lipoprotein cholesterol (LDL-c) (r = − 0.405 and − 0.308, respectively, both P < 0.01). Compared to baseline, significantly lower TMAO levels and higher carnitine, betaine and GBB levels were observed after rosuvastatin therapy, while the lipids decreased significantly (P < 0.05). The significant correlation between TMAO and TG or between betaine and LDL-c disappeared after rosuvastatin therapy (r = 0.050 and − 0.172, respectively, both P > 0.05). However, a significantly positive association between carnitine and TC and a negative association between carnitine and LDL-c or between betaine and TG were found after adjustment for sex, age, body mass index (BMI) and lipids (P < 0.05). Conclusions: This study suggests that TMAO-related metabolites are significantly associated with blood lipids, although some of them are changed postrosuvastatin therapy. Lower TMAO and higher TMAO precursors were observed after rosuvastatin therapy compared to baseline. This study indicates that elevated TMAO precursors after rosuvastatin therapy and their potential impact on ASCVD should be considered in the clinic. [ABSTRACT FROM AUTHOR]

This experiment was conducted to investigate the effects of different supplementation levels of palygorskite and probiotics complex (Pal-Pro) on laying performance, hatching performance, egg quality, plasma antioxidative status, and immune response of broiler breeders. A total of 432 Xuefeng black-bone chickens (42-week-old) were randomly assigned into four treatments with six replicates of 18 hens. The broiler breeders were fed the basal diet supplemented with 0, 250, 500, and 750 mg/kg Pal-Pro for 8 weeks. The Pal-Pro supplementation linearly or quadratically increased (p <.05) laying rate, fertilisation rate, hatchability of fertile eggs, heath hatched chicks rate, eggshell thickness, yolk index, total antioxidant capacity, activities of total superoxide dismutase, catalase, glutathione peroxidase, and contents of immunoglobulins, interleukin-2, and tumour necrosis factor-α in plasma. With Pal-Pro supplementation increased, feed convention ratio during 5–8 and 1–8 week, embryo mortality, malondialdehyde linearly decreased (p <.05). This finding suggested that dietary supplementation with 750 mg/kg Pal-Pro administration could improve the antioxidative status and immunoglobulins contents in plasma of broiler breeders, which may contribute to an increase in broiler's laying rate, hatching performance, egg quality, such as eggshell thickness and yolk index. Dietary supplementation of Pal-Pro decreased the feed conversion ratio and embryo mortality of broiler breeders. Dietary supplementation of Pal-Pro improved the laying rate, fertility, hatchability of fertile eggs, and yolk index of broiler breeders. Dietary supplementation of Pal-Pro enhanced the antioxidant capacity and the level of immunoglobulins in the plasma. [ABSTRACT FROM AUTHOR]

Endothelial cell injury in vascular arterial walls plays a crucial role in the pathological process of atherosclerosis. Pterostilbene, a stilbenoid chemically related to resveratrol, has anti-inflammatory, anti-apoptosis and antioxidant properties. However, the underlying mechanisms mediated by pterostilbene in regards to endothelial cell injury in vascular arterial walls are not fully understood. The purpose of the present study was to investigate the benefits of pterostilbene in a rat model of atherosclerosis. The possible mechanism of pterostilbene was also analyzed in regards to endothelial cell injury in vascular arterial walls in vitro. A rat model of atherosclerosis was established using endothelial injury of the iliac arteries. CCK-8 assay, TUNEL, immunofluorescence, western blot analysis and hematoxylin and eosin (H&E) staining were used to analyze the role of pterostilbene in the pathological processes of atherosclerosis. In vivo results showed that pterostilbene decreased cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) in plasma and attenuated interleukin (IL)-1, tumor necrosis factor (TNF)-α and IL-6 and oxidative stress injury in serum in the experimental animals. Pterostilbene treatment reduced atherogenesis, aortic plaques, macrophage infiltration and apoptosis of vascular arterial walls in the atherosclerosis rat model. In vitro assay demonstrated that pterostilbene administration increased viability of the endothelial cells, attenuated oxidative stress injury and apoptosis of endothelial cells. The results found that pterostilbene regulated endothelial cell apoptosis via the Nrf2-mediated TLR-4/MyD88/NF-κB pathway. In conclusion, data from the present study revealed that pterostilbene protects rats against atherosclerosis by regulation of the Nrf2-mediated TLR-4/MyD88/NF-κB pathway. [ABSTRACT FROM AUTHOR]

In this paper, the artificial intelligence control algorithm for steering robot of steering wheel is studied. The steering movement of wheeled soccer robot is controlled by artificial intelligence control algorithm, and the steering movement is modeled and simulated. Firstly, the characteristics of artificial neurons are simulated and a similar control model is constructed to complete the simulation of football. The artificial intelligence control algorithm has a dynamic feedback item compared with the traditional intelligent model, which has a better effect on the steering control of the wheeled soccer robot. In this paper, artificial intelligence control algorithm is used to optimize the parameters of artificial intelligence control algorithm, and the output of control signal of each steering part of wheeled soccer robot is simulated in the experiment, and the control of the steering action of wheeled soccer robot by artificial intelligence control algorithm is verified by experiments. Then the artificial intelligence control algorithm forms the connection structure. This method provides a good reference for steering control of wheeled soccer robots. [ABSTRACT FROM AUTHOR]

Dihydromyricetin (DHM) is a natural bioactive flavonoid extracted from Ampelopsis Grossedentata , a commonly used Chinese herbal medicine. It has multiple beneficial pharmacological effects including lowering blood glucose and lipid, as well as anti-inflammation, anti-oxidation and hepato-protection. In this study, we elucidated its actions on mitochondrial dynamics and browning of white adipose. In the experiments in vivo , six-week-old male C57BL/6 mice were fed with normal diet (ND), high-fat diet (HFD), or HFD with intragastric administration of DHM (250 mg/kg.d−1); in the experiments in vitro , 3T3-L1 and mouse primary preadipocytes were induced and treated with various concentrations of DHM. The mouse metabolic phenotype, lipid accumulation, the browning and mitochondrial dynamics of white adipocytes were examined. It was found that DHM treatment reduced body weight and fat mass, improved glucose tolerance, insulin resistance and cold tolerance in mice with obesity. DHM treatment increased the expressions of classical brown adipocyte markers (UCP-1, PGC-1α, PRDM16) and mitochondrial dynamics-related proteins (DRP1, FIS1, OPA1, MFN2) in adipose tissue. Likewise, DHM treatment induced the differentiation of mature 3T3-L1 cells into brown-like adipocytes and also enhanced the expressions of mitochondrial dynamics-related proteins in vitro. Moreover, the pro-browning effect of DHM can be abrogated by mitochondrial fission inhibitor Mdivi-1. These findings indicate that DHM treatment induces the browning-remodeling of white adipose by enhancing mitochondrial fission and manifests an anti-obesity property via pro-browning mediated by mitochondrial fission, which implies it may play important roles in prevention and therapy of obesity and related diseases. [Display omitted] • DHM reduces body weights and fat accumulation, improves the homeostasis of glycolipid metabolism and insulin resistance. • DHM promotes the browning of WAT both in vitro and in vivo. • DHM induces the browning-remodeling of WAT by enhancing the mitochondrial fission. [ABSTRACT FROM AUTHOR]

Vascular endothelium dysfunction caused by endothelium inflammation is a trigger of numerous cardiovascular diseases. Vascular endothelium inflammation often occurs in patients with obesity. Asprosin (ASP) derived from white adipose tissue plays important roles in maintaining glucose homeostasis. However, effect of ASP on the vascular endothelium inflammation induced by hyperlipidemia and its underlying mechanism remains largely unclear. In this study, models of vascular endothelium inflammation were established to investigate the effect of ASP on the endothelium inflammation both in vivo and in vitro. Our data in vivo showed that recombinant ASP or high-fat diet (HFD) significantly increased the circulating levels of IL-6 and TNF-α and enhanced the adhesion of macrophages to endothelia characterized by the expression increase of CD68, ICAM-1, and VCAM-1 in rats. However, neutralization of ASP with an ASP specific antibody (AASP) significantly antagonized the changes induced by HFD. Similarly, our data in vitro also showed that ASP treatment elevated the expressions of IL-6, TNF-α, and ICAM-1 as well as VCAM-1. More important, our data revealed that the pro-inflammation effect of ASP was achieved by activating the IKKβ-NF-κBp65 pathway other than the oxidative stress pathway both in vivo and in vitro. In conclusion, our results demonstrate that ASP is a pro-inflammation player in the obesity-associated endothelium dysfunction. The findings would provide a novel target for the prevention and treatment of obesity-related cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Guinea pigs are an alternative small animal model for many disease studies. Here we describe a pan-γδ monoclonal antibody (anti-TCRδ1) specific for the constant region of human T cell receptor delta chains that cross-reacts with a subpopulation of guinea pig (Cavia porcellus) lymphocytes. The phenotype and distribution of this subpopulation is consistent with the guinea pig γδ T cell subset. FACS analysis of fresh PBMC and splenocytes from naïve guinea pigs revealed the presence of a subset of cells that stained with the anti-TCRδ1 mAb. The relative percentage of anti-TCRδ1 positive cells in PBMC and tissues is similar to that described for γδ T cells in other species. Immunohistochemistry of tissues also revealed a distribution of anti-TCRδ1 positive cells consistent with γδ T cells. These data are further supported by staining of a polyclonal guinea pig T cell line that became progressively CD4 and CD8 negative in long-term culture. Analysis of PBMC from guinea pigs following aerosol infection with virulent Mycobacterium tuberculosis revealed no apparent changes in the steady-state percentage of blood γδ+ T cells. Taken together, these data suggest that the anti-TCRδ1 antibody recognizes the γδ T cell subset in guinea pigs. This reagent may be useful for examining γδ T cells in various disease models where the guinea pig is a more desirable model for study. [Copyright &y& Elsevier]

Asprosin (ASP) is a newly‐identified adipokine and plays important roles in energy metabolism homeostasis. However, there is no report on whether and how ASP is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Therefore, in the study, we investigated the protective effects of ASP‐deficiency on the liver in the NAFLD model mice and the detrimental effects of ASP treatment on the human normal hepatocytes (LO2 cell line). More important, we explored the underlying mechanism from the perspective of lipid metabolism and inflammation. In the in vivo experiments, our data showed that the ASP‐deficiency significantly alleviated the high‐fat diet‐induced inflammation and NAFLD, inhibited the hepatic fat deposition and downregulated the expressions of fat acid synthase (FASN), peroxisome proliferator‐activated receptor γ (PPARγ) and forkhead box protein O1 (FOXO1); moreover, the ASP‐deficiency attenuated the inflammatory state and inhibited the activation of the IKK/NF‐κBp65 inflammation pathway. In the in vitro experiments, our results revealed that ASP treatment caused and even exacerbated the injury of LO2 cells induced by FFA; In contrast, the ASP treatment upregulated the expressions of PPARγ, FOXO1, FASN, ACC and acyl‐CoA oxidase 1 (ACOX1) and elevated the reactive oxygen species (ROS) levels. Accordingly, these results demonstrate that ASP causes NAFLD through disrupting lipid metabolism and promoting the inflammation mediated by ROS. [ABSTRACT FROM AUTHOR]

• Increased vascular tones were observed in both diabetic patients and animals. • GLP-1 supplementation improved the mitochondrial functions and vascular tones. • GLP-1 supplementation enhanced adiponectin, AMPK and Sirt1 expressions. • CREB phosphorylation was enhanced by GLP-1 and promoted adiponectin transcription. The dysfunction of vasculature is observed in diabetes and might be responsible for the increased incidence of vascular events. Previous studies indicated that supplementation of GLP-1 analogues is beneficial to the cardiovascular functions in diabetic patients, but the mechanisms are not clear. A type 1 diabetic model was constructed. Vascular constrictions were measured using wire myograph. Western blotting and quantitative PCR were adopted to analyze the expression profiles of key molecules. Mitochondrial functions were analyzed in both vascular tissues or vascular smooth muscle cells (VSMCs). Dual-luciferase reporter assay was used to investigate the mechanism of adiponectin regulation. In this study, abnormal vascular hypertrophy and increased vascular tones were observed in both diabetic patients and animals. ROS productions were increased in vessels and VSMCs from diabetic patients and animals, and the ROS scavenger mitoTEMPO partially attenuated the abnormal vascular tones and hypertension. In addition, decreased GLP-1 levels were observed, while GLP-1 supplementation improved the mitochondrial functions and vascular tones. Furthermore, it was shown that GLP-1 supplementation enhanced adiponectin expressions, while adiponectin facilitated the phosphorylation of AMPK and Sirt1 expressions. Also, CREB phosphorylation was enhanced upon GLP-1 supplementation and promoted the transcriptions of adiponectin. Finally, CREB inhibition partially attenuated the effects of GLP-1 on mitochondrial functions and adiponectin expressions. GLP-1 downregulation might be an important mechanism of abnormal mitochondrial function and vascular tone in diabetes. Targeting GLP-1/CREB/adiponectin axis might become a promising therapeutic strategy in alleviating diabetes-related cardiovascular dysfunctions. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction (ED) is commonly considered a crucial initiating step in the pathogenesis of numerous cardiovascular diseases. The coupling of endothelial nitric oxide synthase (eNOS) is important in maintaining normal endothelial functions. However, it still remains elusive whether and how eNOS SUMOylation affects the eNOS coupling. In the study, we investigate the roles and possible action mechanisms of protein inhibitor of activated STAT 1 (PIAS1) in ED. Human umbilical vein endothelial cells (HUVECs) treated with palmitate acid (PA) in vitro and ApoE−/− mice fed with high‐fat diet (HFD) in vivo were constructed as the ED models. Our in vivo data show that PIAS1 alleviates the dysfunction of vascular endothelium by increasing nitric oxide (NO) level, reducing malondialdehyde (MDA) level, and activating the phosphatidylinositol 3‐kinase‐protein kinase B‐endothelial nitric oxide synthase (PI3K‐AKT‐eNOS) signaling in ApoE−/− mice. Our in vitro data also show that PIAS1 can SUMOylate eNOS under endogenous conditions; moreover, it antagonizes the eNOS uncoupling induced by PA. The findings demonstrate that PIAS1 alleviates the dysfunction of vascular endothelium by promoting the SUMOylation and inhibiting the uncoupling of eNOS, suggesting that PIAS1 would become an early predictor of atherosclerosis and a new potential target of the hyperlipidemia‐related cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: The occurrence of Isolated left subclavian artery (ILSA) is relatively rare, ILSA is caused by the persistence of the dorsal segment of the sixth left arch, with regression of the fourth arch artery and interruption of the left dorsal aorta at the distal end of the seventh intersegmental artery on the left side during embryonic development. The left subclavian artery is connected to the pulmonary artery through an arterial duct, which can be closed or unobstructed. This abnormality can lead to congenital subclavian steal syndrome and vertebrobasilar artery insufficiency. Case presentation: We reported three fetuses with ILSA and intracardiac malformation. Among them, one case was suspected to be diagnosed with ILSA by echocardiography, while the other two cases were not diagnosed, but were accidentally discovered during autopsy. We have also conducted a literature review of its prenatal screening, diagnosis, management, and outcomes. Our three cases were tested by WES‐Trio (whole exome sequencing). Worldwide, the ILSA cases reported in English literature have not been detected by WES. And likely pathogenic results were found in our two cases. Although it could not explain the intracardiac malformation we found, it will help to explore the etiology in the future. Conclusions: Prenatal echocardiography detection and diagnosis of ILSA is a new challenge, which has different effects on the prognosis of the fetus. When finding intracardiac malformation with right aortic arch, we need to perform an unconventional view of ultrasound scanning and combine with CDFI to find the origin of the left subclavian artery. Although we cannot find the cause of the disease temporarily, but our genetic results can help prenatal genetic counseling. [ABSTRACT FROM AUTHOR]

(1) Background: The objective of this study was to investigate the diagnostic value of chromosomal microarray analysis (CMA) for congenital heart defects (CHDs) with different cardiac phenotypes and extracardiac abnormalities (ECAs) and to explore the pathogenic genetic factors of CHDs. (2) Methods: We collected fetuses diagnosed with CHDs by echocardiography at our hospital from January 2012 to December 2021. We analyzed the CMA results of 427 fetuses with CHDs. We then categorized the CHD into different groups according to two dimensions: different cardiac phenotypes and whether it was combined with ECAs. The correlation between the numerical chromosomal abnormalities (NCAs) and copy number variations (CNVs) with CHDs was analyzed. Statistical analyses, including Chi-square tests and t-tests, were performed on the data using IBM SPSS and GraphPad Prism. (3) Results: In general, CHDs with ECAs increased the detection rate for CA, especially the conotruncal defects. CHD combined with the thoracic and abdominal walls and skeletal, thymic and multiple ECAs, were more likely to exhibit CA. Among the CHD phenotypes, VSD and AVSD were associated with NCA, while DORV may be associated with NCA. The cardiac phenotypes associated with pCNVs were IAA (type A and B), RAA, TAPVC, CoA and TOF. In addition, IAA, B, RAA, PS, CoA and TOF were also associated with 22q11.2DS. The length distribution of the CNV was not significantly different between each CHD phenotype. We detected twelve CNV syndromes, of which six syndromes may be related to CHDs. The pregnancy outcome in this study suggests that termination of pregnancy with fetal VSD and vascular abnormality is more dependent on genetic diagnosis, whereas the outcome in other phenotypes of CHDs may be associated with other additional factors. (4) Conclusions: CMA examination for CHDs is still necessary. We should identify the existence of fetal ECAs and specific cardiac phenotypes, which are helpful for genetic counseling and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Asprosin (ASP) is a recently identified adipokine secreted by white adipose tissue (WAT). It plays important roles in the maintenance of glucose homeostasis in the fasting state and in the occurrence and development of obesity. However, there is no report on whether and how ASP would inhibit angiogenesis and fat browning in the mouse adipose microenvironment. Therefore, the study sought to investigate the effects of ASP-knockout on angiogenesis and fat browning, and to identify the interaction between them in the ASP-knockout mouse adipose microenvironment. In the experiments in vivo, the ASP-knockout alleviated the obesity induced by a high fat diet (HFD) and increased the expressions of the browning-related proteins including uncoupling protein 1 (UCP1), PRD1-BF-1-RIZ1 homologus domain-containing protein-16 (PRDM16) and PPAR gamma coactivator 1 (PGC1-α) and the endothelial cell marker (CD31). In the experiments in vitro, treatment with the conditional medium (CM) from ASP-knockout adipocytes (ASP−/−-CM) significantly promoted the proliferation, migration and angiogenesis of vascular endothelial cells, and increased the expressions of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) pathway proteins. In addition, the treatment with CM from endothelial cells (EC-CM) markedly reduced the accumulation of lipid droplets and increased the expressions of the browning-related proteins and the mitochondrial contents. Moreover, the treatment with EC-CM significantly improved the energy metabolism in 3T3-L1 adipocytes. These results highlight that ASP-knockout can promote the browning and angiogenesis of WAT, and the fat browning and angiogenesis can interact in the mouse adipose microenvironment, which contributes to weight loss in the mice with obesity. [ABSTRACT FROM AUTHOR]

Background: Left–right laterality disorders are a heterogeneous group of disorders caused by an altered position or orientation of the thoracic and intra-abdominal organs and vasculature across the left–right axis. They mainly include situs inversus and heterotaxy. Those disorders are complicated by cardiovascular abnormalities significantly more frequently than situs solitus.In this study, 16 patients with a fetal diagnosis of laterality disorder with congenital heart defects (CHD) were evaluated with a single nucleotide polymorphism array (SNP-arry) combined with whole-exome sequencing (WES).Although the diagnostic rate of copy number variations was 0 and the diagnostic rate of WES was 6.3% (1/16), the likely pathogenic gene DNAH11 and the candidate gene OFD1 were ultimately identified. In addition, novel compound heterozygous mutations in the DNAH11 gene and novel hemizygous variants in the OFD1 gene were found. Among the combined CHD, a single atrium/single ventricle had the highest incidence (50%, 8/16), followed by atrioventricular septal defects (37.5%, 6/16). Notably, two rare cases of common pulmonary vein atresia (CPVA) were also found on autopsy.This study identified the types of CHD with a high incidence in patients with laterality disorders. It is clear that WES is an effective tool for diagnosing laterality disorders and can play an important role in future research.Methods: Left–right laterality disorders are a heterogeneous group of disorders caused by an altered position or orientation of the thoracic and intra-abdominal organs and vasculature across the left–right axis. They mainly include situs inversus and heterotaxy. Those disorders are complicated by cardiovascular abnormalities significantly more frequently than situs solitus.In this study, 16 patients with a fetal diagnosis of laterality disorder with congenital heart defects (CHD) were evaluated with a single nucleotide polymorphism array (SNP-arry) combined with whole-exome sequencing (WES).Although the diagnostic rate of copy number variations was 0 and the diagnostic rate of WES was 6.3% (1/16), the likely pathogenic gene DNAH11 and the candidate gene OFD1 were ultimately identified. In addition, novel compound heterozygous mutations in the DNAH11 gene and novel hemizygous variants in the OFD1 gene were found. Among the combined CHD, a single atrium/single ventricle had the highest incidence (50%, 8/16), followed by atrioventricular septal defects (37.5%, 6/16). Notably, two rare cases of common pulmonary vein atresia (CPVA) were also found on autopsy.This study identified the types of CHD with a high incidence in patients with laterality disorders. It is clear that WES is an effective tool for diagnosing laterality disorders and can play an important role in future research.Results: Left–right laterality disorders are a heterogeneous group of disorders caused by an altered position or orientation of the thoracic and intra-abdominal organs and vasculature across the left–right axis. They mainly include situs inversus and heterotaxy. Those disorders are complicated by cardiovascular abnormalities significantly more frequently than situs solitus.In this study, 16 patients with a fetal diagnosis of laterality disorder with congenital heart defects (CHD) were evaluated with a single nucleotide polymorphism array (SNP-arry) combined with whole-exome sequencing (WES).Although the diagnostic rate of copy number variations was 0 and the diagnostic rate of WES was 6.3% (1/16), the likely pathogenic gene DNAH11 and the candidate gene OFD1 were ultimately identified. In addition, novel compound heterozygous mutations in the DNAH11 gene and novel hemizygous variants in the OFD1 gene were found. Among the combined CHD, a single atrium/single ventricle had the highest incidence (50%, 8/16), followed by atrioventricular septal defects (37.5%, 6/16). Notably, two rare cases of common pulmonary vein atresia (CPVA) were also found on autopsy.This study identified the types of CHD with a high incidence in patients with laterality disorders. It is clear that WES is an effective tool for diagnosing laterality disorders and can play an important role in future research.Conclusion: Left–right laterality disorders are a heterogeneous group of disorders caused by an altered position or orientation of the thoracic and intra-abdominal organs and vasculature across the left–right axis. They mainly include situs inversus and heterotaxy. Those disorders are complicated by cardiovascular abnormalities significantly more frequently than situs solitus.In this study, 16 patients with a fetal diagnosis of laterality disorder with congenital heart defects (CHD) were evaluated with a single nucleotide polymorphism array (SNP-arry) combined with whole-exome sequencing (WES).Although the diagnostic rate of copy number variations was 0 and the diagnostic rate of WES was 6.3% (1/16), the likely pathogenic gene DNAH11 and the candidate gene OFD1 were ultimately identified. In addition, novel compound heterozygous mutations in the DNAH11 gene and novel hemizygous variants in the OFD1 gene were found. Among the combined CHD, a single atrium/single ventricle had the highest incidence (50%, 8/16), followed by atrioventricular septal defects (37.5%, 6/16). Notably, two rare cases of common pulmonary vein atresia (CPVA) were also found on autopsy.This study identified the types of CHD with a high incidence in patients with laterality disorders. It is clear that WES is an effective tool for diagnosing laterality disorders and can play an important role in future research. [ABSTRACT FROM AUTHOR]

Background: Dipeptidyl peptidase-4 inhibitors (DPP-4i) decrease glucose levels by regulating incretin peptides in type 2 diabetes mellitus (T2DM). This study aimed to determine the modulatory effect of DPP-4i on brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in patients with T2DM. Methods: PubMed, Embase and the Cochrane Library were systematically searched to identify randomized controlled trials (RCTs) evaluating the impact of DPP-4i on BNP or NT-pro-BNP. A fixed- or random-effects model was used for quantitative analysis, according to the heterogeneity. Sensitivity analysis and publication bias were performed using standard methods. Results: Nine trials with 3056 patients with T2DM were included. Meta-analysis revealed that DPP-4i did not significantly modulate the BNP (0.21 pg/mL, 95% CI − 2.36–2.79) or NT-pro-BNP level (− 7.34 pg/mL, 95% CI − 24.27–9.59). DPP-4i demonstrated no stronger effect on modulating BNP (5.17 pg/mL, 95% CI − 7.48–17.82) or NT-pro-BNP (− 9.95 pg/mL, 95% CI − 44.61–24.71) than active comparators. Pooled analysis was robust and stable after sensitivity analysis. Conclusions: DPP-4i exhibits no significant effect on modulating BNP or NT-pro-BNP and shows no stronger effect than traditional antidiabetic agents in T2DM. [ABSTRACT FROM AUTHOR]

The aim of our study was to compare overfeeding performance, fatty acid composition, enzymes activity and gene expression between overfed Xupu geese with large and small liver. A total of sixty 80 d male Xupu geese were overfed by the same feed intake under the same conditions. The liver weight exhibited normal distribution. Based on the weight of liver, samples were divided into large liver (LL) and small liver (SL) Xupu geese. After overfeeding for 28 d: compared with the SL-Xupu geese, liver weight and liver-to-body weight ratio increased (p <.05), while abdominal fat weight and feed-to-liver weight ratio decreased (p <.05); the level of palmitic acid and methyltetracosanoate acid decreased (p <.05), and the level of oleic acid, linoleic acid, arachidonic acid, and docosahexaenoic acid increased (p <.05) in liver of LL-Xupu geese. Compared with the SL-Xupu geese, LL-Xupu geese had a higher plasma concentration of TG (triglyceride) (p <.05), and had a lower plasma concentration of VLDL-C (very low density lipoprotein cholesterol) (p <.05); and had a higher CHE (cholinesterase), LPS (lipase), LPL (lipoproteinlipase) activities (p <.05) in the liver. The mRNA expression of FABP4 (adipocyte fatty acid binding protein), SCD (stearoyl-CoA desaturase), FADS (fatty acid dehydrogenase), ELOVL1 (elongase of long-chain fatty acid 1), ACAT2 (acyl-Co A: cholesterol acyltransferase 2), and FASN (fatty acid synthase) (p <.05) were significantly upregulated in LL-Xupu geese than in SL-Xupu geese. The results showed that the level of unsaturated fatty acid in liver of LL-Xupu geese was higher than that of SL-Xupu geese, which may be closely related to enzymes and genes expression related to lipid metabolism. The content of unsaturated fatty acids in liver of LL-Xupu geese were significantly higher than in SL-Xupu geese. The mRNA expression of FABP4, SCD, FADS, ELOVL1, ACAT2, and FASN were significantly upregulated in LL-Xupu geese than in SL-Xupu geese. The level of unsaturated fatty acid in liver of LL-Xupu geese was higher than that of SL-Xupu geese, which may be closely related to enzymes and genes expression related to lipid metabolism. [ABSTRACT FROM AUTHOR]

Highlights • The specific scanning process was used obtain shape information of aggregate. • FEI, SI and SSA are proposed to characterize the morphology of aggregate. • The minimum bounding box algorithm was developed to calculate FEI of aggregate. • Abrasion decay laws of the quantitative indexes were illustrated by image analysis. Abstract In order to quantitatively evaluate morphological characteristics and abrasion decay laws of coarse aggregate so that make an accurate performance evaluation for aggregates, flat-elongated index, sphericity index and specific surface area are proposed to characterize the shape properties of coarse aggregate. Limestone aggregate particles ranging in size scale of 4.75–9.5 mm, 9.5–13.2 mm, 19–26.5 mm were worn by the Los Angeles Abrasion tester respectively. Three-dimensional (3-D) laser scanner was used to obtain three-dimensional points cloud data of aggregate particles experienced 0, 500, 1000 and 2000 abrasion cycles. Afterwards, the data was processed by the software of reverse engineering based on morphology evaluation indexes, and the minimum bounding box algorithm was developed to calculate flat-elongated index, illustrating the morphological characteristics of coarse aggregate particles with different size and abrasion cycles. Test results show that: aggregates with small size have bigger quantity proportion of elongated particle; the greater the angularity of aggregates was, the faster the angular decay rate of the aggregates was; aggregate particles with small size has richer surface texture but easier to lost in abrasion process. Sphericity index increased, while specific surface area and flat-elongated index presented a downward trend as the particle size became bigger for different abrasion cycles. However, the flat-elongated index of aggregate particles with different size increased abnormally when abrasion cycles increased at 2000 abrasion cycles as the result of aggregate crushing. Besides, the sphericity and specific surface area of some 4.75 mm aggregate under 500 abrasion cycles showed an abnormal increasing compared to its 1000 abrasion cycles, which caused by inadequate abrasion under low abrasion cycles. Therefore, the indexes proposed in the study are able to characterize different aspects of coarse aggregates morphological property, and it is beneficial for the evaluation and selection of aggregates used in engineering construction. [ABSTRACT FROM AUTHOR]

PPARγ1 and FOXO1 are the key transcription factors that regulate insulin sensitivity. We previously found that a small ubiquitin-related modifier of PPARγ1 at K77 (SUMOylation) favored endothelial insulin resistance (IR) induced by high fat/high glucose (HF/HG) administration. However, whether and how the crosstalk between SUMOylated PPARγ1 and FOXO1 would mediate the development of the endothelial IR and dysfunction remains unclear. Here, we emphasize how PPARγ1-K77 SUMOylation would interact with FOXO1 and participate in the development of the endothelial IR and dysfunction. Our results show that the combination of HF/HG and PPARγ1-K77 SUMOylation exhibits a synergistic deteriorative effect on the endothelial IR and dysfunction, presenting decreased NO levels and elevated ET-1 levels, weakened PI3K/Akt/eNOS signaling, and impaired endothelium-dependent vasodilation function. The further researches reveal that PPARγ1-K77 SUMOylation readily interacts with FOXO1, and FOXO1 occupies the PPAR response element (PPRE) which is supposed to be occupied by PPARγ, thus resulting in the decrease of PPARγ1 transcription activity and the mitigation of the PI3K/Akt signaling. Moreover, the mitigation of the PI3K/Akt signaling promotes in turn the accumulation of FOXO1 in the nucleus where FOXO1 interacts with the SUMOylated PPARγ1, thus exerting a positive feedback effect on IR pathogenesis. The findings uncover a novel association between PPARγ1-K77 SUMOylation and FOXO1, which contributes to our understanding of the pathogenesis of endothelial IR and dysfunction and provides novel pharmacological targets for diabetic angiopathy. [Display omitted] • PPARγ1-K77 SUMOylation combined with HF/HG exhibits a synergistic deteriorative effect on the endothelial IR and dysfunction. • PPARγ1-K77 SUMOylation impairs rats endothelium-dependent vasodilation. • FOXO1 blocks the PPRE binding site on PI3K and represses the PPARγ transcription activity via PPARγ1-K77 SUMOylation. • PPARγ1-K77 SUMOylation causes FOXO1 nuclear accumulation by negatively regulating FOXO1 phosphorylation via PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

Daidzein has been found to significantly inhibit the proliferation of lung cancer cells, while its potential molecular mechanisms remain unclear. To determine the molecular mechanism of daidzein on lung cancer cells, the Capital Bio Technology Human long non-coding (lnc) RNA Array v4, 4×180K chip was used to detect the gene expression profiles of 40,000 lncRNAs and 34,000 mRNAs in a human cancer cell line. Reverse transcription-quantitative (RT-q) PCR analysis was performed to detect the expression levels of target lncRNA and mRNAs in the H1299 cells treated with and without daidzein, using the lncRNA and mRNA gene chip. Bioinformatics analysis was performed to determine the differentially expressed genes from the results of the chip assays. There were 119 and 40 differentially expressed lncRNAs and mRNAs, respectively, that had a 2-fold change in expression level. A total of eight lncRNAs were upregulated in the H1299 lung cancer cells, while 111 lncRNAs were downregulated. Furthermore, five mRNAs were upregulated, and 35 mRNAs were downregulated. A total of six differentially expressed lncRNAs (ENST00000608897.1, ENST00000444196.1, ENST00000608741.1, XR_242163.1, ENST00000505196.1 and ENST00000498032.1) were randomly selected to validate the microarray data, which were consistent with the RT-qPCR analysis results. Differentially expressed mRNAs were enriched in important Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Taken together, the results of the present study demonstrated that daidzein affected the expression level of lncRNAs in lung cancer cells, suggesting that daidzein may have potential effects on lung cancer cells. [ABSTRACT FROM AUTHOR]

Both microbial products and T cell factors influence dendritic cell (DC) maturation. However, it is not known which T cells are capable of interacting with DCs at the initiation of adaptive immunity, when foreign antigen-specific T cells are rare. We show here that self-reactive CDI-restricted T cells can promote DC maturation by recognizing CDI in the absence of foreign antigens. T cell recognition of all four CDI isoforms can trigger DC maturation, but their distinct mechanisms of costimulation lead to profound differences in concomitant interleukin 12 p70 production. Distinct CDI-reactive T cells may thus differentially direct DC development early in the immune response, thereby controlling subsequent polarization of acquired immunity. [ABSTRACT FROM AUTHOR]

As a flavonoid, naringin (Nar) has been shown to have multiple pharmacological effects including lowering blood cholesterol, reducing thrombus formation and improving microcirculation. However, effects of Nar on function and autophagy of vascular endothelial cells under high glucose and high fat (HG/HF) stress are largely unclear. This study was designed to investigate such effects of Nar in human umbilical vein endothelial cells (HUVECs) and to determine whether such effects are related to autophagy. Our present results show that 86 μM of Nar inhibits the autophagy levels and protects the cells against the dysfunction induced by HG/HF stress. Moreover, Nar increases the phosphorylation levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) and mammalian rapamycin target protein (mTOR). However, pretreatment with rapamycin (RAPA, 5 μM, autophagy inducer), LY294002(10 μM, PI3K inhibitor) and Akt inhibitor Ⅳ (0.5 μM, Akt inhibitor) partially abrogates the protective effects of Nar, suggesting that the protective effects of Nar are achieved by activating the PI3K-Akt-mTOR pathway to inhibit autophagy. In conclusion, Nar improves the function of HUVECs under HG/HF stress through activating the PI3K-Akt-mTOR pathway to inhibit autophagy. The findings offer an insight into HG/HF stress-induced autophagy and indicate that Nar might have potential to prevent and treat the diabetic angiopathy. Image 1 [ABSTRACT FROM AUTHOR]