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BackgroundDiabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Hence, early detection of cardiac changes by imaging is crucial to reducing cardiovascular complications.PurposeEarly detection of cardiac changes is crucial to reducing cardiovascular complications. The study aimed to detect the dynamic change in cardiac morphology, function, and diffuse myocardial fibrosis(DMF) associated with T1DM and T2DM mice models.Materials and methods4-week-old C57Bl/6J male mice were randomly divided into control (n=30), T1DM (n=30), and T2DM (n=30) groups. A longitudinal study was conducted every 4 weeks using serial 7.0T CMR and echocardiography imaging. Left ventricular ejection fraction (LV EF), tissue tracking parameters, and DMF were measured by cine CMR and extracellular volume fraction (ECV). Global peak circumferential strain (GCPS), peak systolic strain rate (GCPSSR) values were acquired by CMR feature tracking. LV diastolic function parameter (E/E’) was acquired by echocardiography. The correlations between the ECV and cardiac function parameters were assessed by Pearson’s test.ResultsA total of 6 mice were included every 4 weeks in control, T1DM, and T2DM groups for analysis. Compared to control group, an increase was detected in the LV mass and E/E’ ratio, while the values of GCPS, GCPSSR decreased mildly in DM. Compared to T2DM group, GCPS and GCPSSR decreased earlier in T1DM(GCPS 12W,P=0.004; GCPSSR 12W,P=0.04). ECV values showed a significant correlation with GCPS and GCPSSR in DM groups. Moreover, ECV values showed a strong positive correlation with E/E’(T1DM,r=0.757,P

Abstract Background Neutrophils consume a large amount of energy when performing their functions. Compared with other white blood cells, neutrophils contain few mitochondria and mainly rely on glycolysis and gluconeogenesis to produce ATP. The inflammatory site is hypoxic and nutrient poor. Our aim is to study the role of abnormal adenosine metabolism of neutrophils in the asthmatic airway inflammation microenvironment. Method In this study, an asthma model was established by intratracheal instillation of Aspergillus fumigatus extract in Ecto-5'-Nucleotidase (CD73) gene–knockout and wild-type mice. Multiple analyses from bronchoalveolar lavage fluid (BALF) were used to determine the levels of cytokines and chemokines. Immunohistochemistry was used to detect subcutaneous fibrosis and inflammatory cell infiltration. Finally, adenosine 5’-(α, β-methylene) diphosphate (APCP), a CD73 inhibitor, was pumped subcutaneously before Aspergillus attack to observe the infiltration of inflammatory cells and subcutaneous fibrosis to clarify its therapeutic effect. Result PAS staining showed that CD73 knockout inhibited pulmonary epithelial cell proliferation and bronchial fibrosis induced by Aspergillus extract. The genetic knockdownof CD73 significantly reduced the production of Th2 cytokines, interleukin (IL)-4, IL-6, IL-13, chemokine (C–C motif) ligand 5 (CCL5), eosinophil chemokine, neutrophil IL-17, and granulocyte colony-stimulating factor (G-CSF). In addition, exogenous adenosine supplementation increased airway inflammation. Finally, the CD73 inhibitor APCP was administered to reduce inflammation and subcutaneous fibrosis. Conclusion Elevated adenosine metabolism plays an inflammatory role in asthma, and CD73 could be a potential therapeutic target for asthma.

Abstract Background Acute type A aortic dissection (ATAAD) is a life-threatening condition that requires surgical intervention. Stroke remains an extremely serious adverse outcome that can occur in ATAAD patients undergoing aortic arch repair, leading to higher rates of patient mortality and decreased postoperative quality of life. In the present study, we sought to determine whether carotid intima–media thickness (cIMT) is a reliable predictor of postoperative stroke risk. Materials and methods This was a prospective study of 76 patients with ATAAD undergoing aortic arch repair. For all patients, cIMT was determined preoperatively through a Doppler-based method. Incidence of different forms of neurological dysfunction, including temporary neurological dysfunction (TND) and stroke, was monitored in these patients, and the relationship between cIMT and stroke incidence was assessed using a receiver-operating characteristic (ROC) curve. Prognostic variables associated with stroke risk were further identified through univariate and multivariate analyses. Results A total of 26/76 (34.2%) patients in the present study suffered from neurological dysfunction, of whom 16 (21.0%) suffered from TND and 10 (13.2%) suffered a stroke. The remaining 50 patients (65.8%) did not suffer from neurological dysfunction. The cIMT values in the stroke, TND, and neurological dysfunction-free patients in this study were 1.12 ± 0.19 (mm), 0.99 ± 0.13 (mm), and 0.87 ± 0.13 (mm), respectively. A total of 4 patients in this cohort died during the study, including 1 in the TND group and 3 in the stroke group. An ROC curve analysis indicated that cIMT could predict stroke with an area under the curve value of 0.844 (95% CI, 0.719–0.969; p 0.9 mm was independently associated with stroke risk (p = 0.018). Conclusion We found that cIMT can be used to predict postoperative stroke risk in ATAAD patients undergoing aortic arch repair, with a cIMT > 0.9 mm coinciding with increased stroke risk in these patients. Trial registration ChiCTR1900022289 . Date of registration 4 April 2019 retrospectively registered.

Background: Matrix metalloproteinase (MMP)-2 plays an important role in the remodeling of left ventricles (LVs) and right ventricles (RVs). We investigated the differences of MMP-2 expression between LV and RV in response to nandrolone decanoate (ND), swimming training (ST), and combined ND and ST (NS) in mice, based on their structural, functional, and biochemical characteristics. Methods: Totally 28 male C57B1 mice (6 weeks old; 20–23 g) were divided into four groups, including the control (n = 7), ND (n = 6), ST (n = 8), and NS (n = 7) groups. After respective treatments for 8 weeks, echocardiographic examination was used to assess the cardiac structure and function. Van Gieson stain was used to examine the fibrosis of LV and RV in response to different treatments, and Western blotting analysis was performed to explore different MMP-2 expressions between LV and RV in response to ND and/or ST. Analysis of variance was used for comparing the four groups. Results: At 8 weeks, right ventricular dimension/body weight in the ND group was larger than the other three groups (F = 7.12, P < 0.05) according to the echocardiographic examination. Fibrosis induced by ND administration was increased more in RV (2.59%) than that in LV (2.21%). MMP-2 expression of the ND group in RV was significantly greater than the control and NS groups in RV and the corresponding ND group in LV. Conclusion: The experimental data support the hypothesis that ND administration induces greater MMP-2 expression increase in RV compared to LV, leading to consequent RV dilation.

Background: Vein graft failure (VGF) is a serious complication of coronary artery bypass graft, although the mechanism remains unclear. The study aimed to investigate the effects of microRNAs (miRNAs) on the endothelial dysfunction involved in VGF. Methods: Human umbilical vein endothelial cells (HUVECs) were subjected to mechanical stretch stimulation to induce endothelial dysfunction. Genome-wide transcriptome profiling was performed using the Human miRNA OneArray® V4 (PhalanxBio Inc., San Diego, USA). The miRNA-messenger RNA (mRNA) network was investigated using gene ontology and Kyoto Encyclopedia of Genes and Genomes. The miR-551b-5p mimic and inhibitor were applied to regulate miR-551b-5p expression in the HUVECs. The 5-ethynyl-2'-deoxyuridine assay, polymerase chain reaction (PCR), and Western blotting (WB) were used to assess HUVECs proliferation, mRNA expression, and protein expression, respectively. The vein graft model was established in early growth response (Egr)-1 knockout (KO) mice and wide-type (WT) C57BL/6J mice for pathological and immunohistochemical analysis. Endothelial cells isolated from the veins of WT and Egr-1 KO mice were subjected to mechanical stretch stimulation; PCR and WB were conducted to confirm the regulatory effect of Egr-1 on Intercellular adhesion molecule (Icam-1). One-way analysis of variance and independent t-test were performed for data analysis. Results: Thirty-eight miRNAs were differentially expressed in HUVECs after mechanical stretch stimulation. The bioinformatics analysis revealed that Egr-1 might be involved in VGF and was a potential target gene of miR-551b-5p. The mechanical stretch stimulation increased miR-551b-5p expression by 2.93 ± 0.08 fold (t = 3.07, P < 0.05), compared with the normal HUVECs. Transfection with the miR-551b-5p mimic or inhibitor increased expression of miR-551b-5p by 793.1 ± 171.6 fold (t = 13.84, P < 0.001) or decreased by 26.3% ± 2.4% (t = 26.39, P < 0.05) in the HUVECs, respectively. HUVECs proliferation and EGR-1 mRNA expression were significantly suppressed by inhibiting miR-551b-5p expression (P < 0.05). The lumens of the vein grafts in the Egr-1 KO mice were wider than that in the WT mice. Icam-1 expression was suppressed significantly in the Egr-1 KO vein grafts (P < 0.05). Conclusions: Increased miR-551b-5p expression leads to endothelial dysfunction by upregulating Egr-1 expression. EGR-1 KO can improve the function of a grafted vein through suppressing Icam-1.

A new linear time algorithm is described for generating four independent spanning trees that are used for data broadcasting in networks, each with a reduced height. The analysis has shown improvements in the reduced heights of these trees, which are helpful in lowering the number of steps in data transmitting.

An efficient algorithm that takes O(m alpha(m, n)) time for finding a detour-critical edge in a shortest path tree is proposed. A special data structure, called transmuter is applied in the algorithm.

By using human genomic DNA as a template to clone protection of telomere 1 (POT1) promoter gene segments and construct the POT1 promoter luciferase report gene vector (pGL3‑Control‑POT1‑promoter), the association between POT1, and the regulation of telomerase and telomere length was investigated. In the present study, two recombinant luciferase report gene vectors were constructed, which included different regions of the POT1 promoter. The plasmids were transformed into DH5α and the positive clones were obtained. The two plasmids termed as pGL3‑Control‑POT1‑promoter‑1 and pGL3‑Control‑POT1‑promoter‑2, were confirmed using restriction enzyme analysis and sequencing. They were separately and transiently transfected into four types of human tumor cells (A549, H460, HepG2 and HeLa). The transcriptional activities of the POT1 promoter were verified using the dual‑luciferase assay. The relative expression of POT1 and human telomerase reverse transcriptase (hTERT), and telomere length were analyzed using quantitative polymerase chain reaction in the four types of non‑transfected tumor cells. Using SPSS software, correlations between POT1 promoter activity, and POT1 expression, hTERT expression and telomere length were analyzed. Two POT1 promoter fragments (POT1‑promoter‑1 and ‑2) were successfully constructed into the pGL3‑Control luciferase report gene vector. POT1‑promoter‑1 exhibited significantly stronger transcription activity compared with POT1‑promoter‑2. The results of the partial correlation and linear regression analyses were similar: POT1 promoter activity was identified to be significantly and positively correlated with POT1 expression and telomere length (partial correlation coefficients, both P<0.05; linear regression, both P<0.01). However, POT1 promoter activity and hTERT expression were significantly negatively correlated (both P<0.05). The results obtained in the present study suggest that the POT1 promoter influences telomere length. Furthermore, these data indicated that POT1 promoter activity and POT1, as well as telomere length, may be a useful biomarker for tumor detection and future patient prognosis. [ABSTRACT FROM AUTHOR]

Overexpression of the survivin gene contributes to tumorigenesis; it has been recognized as an important target for cancer therapy. In the present study, survivin expression was suppressed using recombinant plasmid mediated short hairpin RNAs (shRNAs) that were constructed to target exonic or intronic sequences of the survivin gene. In addition, a negative control shRNA was constructed. HeLa cells were transfected with specific shRNA constructs and the blocking efficiency of each shRNA was assessed at the mRNA and protein levels; and the five shRNA constructs with higher blocking efficiency were selected. Cell apoptosis was assessed by flow cytometry (FCM) following Annexin V-fluorescein isothiocyanate/propidium iodide double staining. Hoechst staining was used to detect the morphological diversity of the nuclei in apoptotic cells. The results demonstrated that survivin expression was effectively reduced by the transfection of shRNAs in HeLa cells. In addition, the apoptotic rates of the shRNA-treated groups were significantly increased compared with the negative control group according to the FCM results. The nuclei of HeLa cells exhibited apoptotic characteristics in the shRNA-treated groups as identified by Hoechst staining. Survivin-targeting shRNAs effectively downregulated the expression of the gene and markedly increased the apoptotic rate of HeLa cells. Data from the present study also indicated that the intron-specific shRNA demonstrate a high efficiency of inhibition of survivin expression and were able to induce cell apoptosis of HeLa cells through RNAi, potentially providing novel target sites for tumor therapy. In conclusion, the present study suggests that intron-specific blocking of survivin by RNAi may provide a tool for anticancer therapy. [ABSTRACT FROM AUTHOR]

The aim of the present study was to construct a fast-acting, eukaryotic expression vector in eukaryotic cells based on transmembrane-tumor necrosis factor-α (TM-TNF-α) structure. Two types of recombinant eukaryotic expression vectors were constructed, pcDNA3.1-TM-enterokinase-TNF-α and pcDNA3.1-TM-Factor Xa-TNF-α, according to the TNF-α transmembrane segments. Following the generation of these vectors, mouse embryonic 3T3 fibroblasts were transfected and reverse transcription-polymerase chain reaction and western blotting analyses were used to analyze mTNF-α mRNA and protein expression levels, respectively, in total cellular protein extracts and extracellular fluid. The biological activity of TNF-α in the extracellular fluid was then measured using an MTT assay. The vectors were successfully constructed, and mRNA and fusion proteins were detected in the 3T3 cells. Among the fusion proteins, the one observed in pcDNA3.1-TM-FactorXa-TNF-α-transfected 3T3 cells remained as a transmembrane protein. In addition, treatment of L929 cells with TNF-α derived extracellular fluid samples from pcDN A3.1-TM-FactorXa-TNF-α-transfected 3T3 cells was associated with a dose-dependent reduction in in cell-specific activity. The results indicate that proteins expressed using pcDNA3.1-TM-FactorXa-TNF-α vectors form transmembrane proteins. In addition, the results indicate that, only when coupled with FactorXa activity, the extracellular region of TM-TNF-α forms s-TNF-α, and the controlled expression of the fusion protein is initiated. [ABSTRACT FROM AUTHOR]

Given two strings X and Y and a constraining string P, a string Z is called a constrained longest common subsequence of X and Y with respect to P if Z is the longest common subsequence of X and Y such that P is a subsequence of Z. In this paper, we propose an O(r x min{mN, nM})-time algorithm for solving this problem, where m, n and r are the lengths of X, Y and P, respectively, and M and N are the number of runs of the run-length-encoded strings of X and Y, respectively. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate and compare multiple daily injection (MDI) therapy of bolus insulin aspart and basal insulin glargine with continuous subcutaneous insulin infusion (CSII) with aspart in patients with type 2 diabetes mellitus (T2DM). It was assessed whether MDI was capable of controlling glycemic index with a higher efficacy than CSII by preferential adjustment of basal insulin with a lower total daily insulin dosage in T2DM. Two hundred patients with T2DM were enrolled in the study and randomly assigned to CSII (n=100) and MDI (n=100; aspart immediately prior to each meal and glargine at bedtime) groups for 12 weeks of therapy. During the last week of each treatment period, the subjects wore a continuous glucose monitoring system for 2-3 days. The dosage of basal insulin was preferentially adjusted to control prior-meal blood glucose levels, and the characteristics of insulin dosage were analyzed. No statistically significant differences were observed between the two groups in hemoglobin A1c (HbA1c), which dropped from 10-11% prior to therapy to 7-7.5% after 12 weeks. After 12 weeks, good glycemic level control was achieved in all patients in the MDI and CSII groups. A statistically significant difference in the dose of insulin between the CSII and MDI groups was observed (P<0.001). In conclusion, no significant differences were found between the two therapies in the incidence of hypoglycemia and HbA1c for the 12 weeks. The basal insulin dosage was significantly decreased in the MDI group compared with that in the CSII group, but the CSII group was superior to MDI group in decreasing fasting blood glucose and shortening the time required for hypoglycemia to meet the targeted level. [ABSTRACT FROM AUTHOR]

The power domination problem is to find a minimum placement of phase measurement units (PMUs) for observing the whole electric power system represented by a graph G. The number of such a minimum placement of PMUs is called the power domination number of G and is denoted by γp(G). Finding γp(G) of an arbitrary graph is known to be NP-complete. In this paper, we deal with the power domination problem on honeycomb meshes. For a t-dimensional honeycomb mesh HMt, we show that γp(HMt) = ...2t/3.... In particular, we present an O(t)-time algorithm as the placement scheme. [ABSTRACT FROM AUTHOR]

An ordered tree is called a non-regular tree with a prescribed branching sequence (or non-regular tree for short) if its internal nodes have a prespecified degree sequence in preorder list. We define a concise representation, called right distance sequences to describe such trees. A coding tree helps us to systematically investigate the structural representation of non-regular trees. Consequently, we present a loopless algorithm to generate Gray-codes of non-regular trees using right distance sequences. [ABSTRACT FROM PUBLISHER]

A recursive circulant graph G(N,d) has N = cdm vertices labeled from 0 to N - 1, where d ⩾ 2, m ⩾ 1, and 1 ⩽ c < d, and two vertices x,y ∈ G(N,d) are adjacent if and only if there is an integer k with 0 ⩽ k ⩽ ⌈logd N⌉ - 1 such that x ± dk ≡ y (mod N). With the aid of recursive structure, such class of graphs has many attractive features and was considered as a topology of interconnection networks for computing systems. The design of multiple independent spanning trees (ISTs) has many applications in network communication. For instance, it is useful for fault-tolerant broadcasting and secure message distribution. In the previous work of Yang et al. (2009), we provided a constructing scheme to build k ISTs on G(cdm,d) with d ⩾ 3, where k is the connectivity of G(cdm,d). However, the proposed constructing rules cannot be applied to the case of d = 2. For the integrity of solving the IST problem on recursive circulant graphs, this paper deals with the case of G(2m,2) using a set of different constructing rules. Especially, we show that the heights of ISTs for G(2m,2) are lower than the known optimal construction of hypercubes with the same number of vertices. [ABSTRACT FROM AUTHOR]

A Δ-interchange is a transformation which reverses the orientations of the arcs in a 3-cycle of a digraph. Let $${\fancyscript T}(S)$$ be the collection of tournaments that realize a given score vector S. An interchange graph of S, denoted by G( S), is an undirected graph whose vertices are the tournaments in $${\fancyscript T}(S)$$ and an edge joining tournaments $$T,T' \in {\fancyscript T}(S)$$ provided T′ can be obtained from T by a Δ-interchange. In this paper, we find a set of score vectors of tournaments for which the corresponding interchange graphs are hypercubes. [ABSTRACT FROM AUTHOR]

Abstract  Periodic Broadcasting schemes are cost- effective methods of implementation of Near Video on Demand systems. While the schemes enjoy the advantage of reducing the demand on server bandwidth, they suffer from the problem of insensitivity to the popularity of videos. However, the popularity of a video does not remain constant in the real world; it varies with time, social events, and so on. From a service provider’s viewpoint, given a set of popular videos and limited server bandwidth, it would be desirable to adjust the bandwidth allocated to each of the videos dynamically and seamlessly according to the level of its hotness. In this paper, we first re-formulate the Generalized Fibonacci Broadcasting as the Fixed-Length Segment- Scheduling problem and name the re-formulated scheme the Slotted Generalized Fibonacci Broadcasting (SGFB). We then propose a seamless channel transition enhancement on top of the SGFB scheme so that the service provider is capable of adjusting the channel allocation policy to make the most benefit out of the available bandwidth. The correctness of SGFB together with its performance analysis will be presented. Furthermore, we shall provide mathematical analysis to demonstrate its channel transition behavior. [ABSTRACT FROM AUTHOR]

Purpose: To observe the short-term dynamic change in serum CXC chemokine ligand-10 (CXCL10) levels in patients with Graves' disease (GD) before and after iodine therapy and to analyze the relationship between CXCL10 levels and clinical disease indices. Methods: ELISA was used to determine serum levels of CXCL10 in 43 patients with GD shortly before radioiodine therapy and on days six, 14, and 60, post-therapy. Results: Patients with newly diagnosed GD showed significantly higher levels of serum CXCL10 compared with the control group (P < 0.01). The serum CXCL10 level increased slightly on day six after treatment of radioactive iodine (P<0.01). There was no significant statistical difference in serum CXCL10 levels pre-treatment and on day 14 post-treatment. A significant reduction in serum CXCL10 level was observed on day 60 (P<0.01). GD patients with exophthalmia showed higher serum CXCL10 level than GD patients without exophthalmia. No correlation was found between levels of CXCL10 and FT3, FT4 or TSH at any time point, but significant positive correlation was shown between thyroid peroxidase antibodies (TPOAb) and CXCL10 (r=0.50, P<0.01). Conclusion: CXCL10 participates in the early inflammatory response after radioactive iodine therapy in patients with Graves' disease and shows a strong association with the autoimmune process. [ABSTRACT FROM AUTHOR]