The heavy metal-associated isoprenylated plant protein (HIPP) gene family plays a crucial role in cadmium resistance and accumulation in the tea plant (Camellia sinensis L.).

Heavy metal-associated isoprenylated plant proteins (HIPPs) are only distributed in vascular plants, and are essential for the detoxification and vascular transport of heavy metals in plants. However, the HIPP gene family has not been thoroughly explored in the tea plant (Camellia sinensis). In this study, we systematically identified 56C. sinensis CsHIPP genes from five groups and characterized their phylogeny, structures, and the features of the encoded proteins. The expression patterns of CsHIPP genes in various tissues of C. sinensis were investigated based on a previous RNA-seq data analysis. The expression patterns of CsHIPP genes were explored in cadmium (Cd)-treated C. sinensis roots using our RNA-seq data. Three CsHIPP genes (CsHIPP22, CsHIPP24, and CsHIPP36) with high expression levels in Cd-treated C. sinensis roots were selected as candidate genes associated with Cd tolerance. Overexpression of CsHIPP22, CsHIPP24, and CsHIPP36 in a yeast mutant (ycf1) rescued Cd-sensitive ycf1 yeast and increased the yeast resistance to Cd stress, implying that these three CsHIPPs might be involved in Cd tolerance. These findings will enable the roles of HIPPs in Cd absorption and detoxification to be better understood as well as improving our understanding of the Cd-resistance and Cd-accumulation mechanisms in tea plant.

Single-Cell Sequencing Revealed Pivotal Genes Related to Prognosis of Myocardial Infarction Patients.

Objectives: Myocardial infarction (MI) is a common cardiovascular disease. Histopathology is a main molecular characteristic of MI, but often, differences between various cell subsets have been neglected. Under this premise, MI-related molecular biomarkers were screened using single-cell sequencing. Methods: This work examined immune cell abundance in normal and MI samples from GSE109048 and determined differences in the activated mast cells and activated CD4 memory T cells, resting mast cells. Weighted gene coexpression network analysis (WGCNA) demonstrated that activated CD4 memory T cells were the most closely related to the turquoise module, and 10 hub genes were screened. Single-cell sequencing data (scRNA-seq) of MI were examined. We used t-distributed stochastic neighbor embedding (t-SNE) for cell clustering. Results: We obtained 8 cell subpopulations, each of which had different marker genes. 7 out of the 10 hub genes were detected by single-cell sequencing analysis. The expression quantity and proportion of the 7 genes were different in 8 cell clusters. Conclusion: In general, our study revealed the immune characteristics and determined 7 prognostic markers for MI at the single-cell level, providing a new understanding of the molecular characteristics and mechanism of MI.

Weighted correlation network bioinformatics uncovers a key molecular biosignature driving the left-sided heart failure.

BACKGROUND: Left-sided heart failure (HF) is documented as a key prognostic factor in HF. However, the relative molecular mechanisms underlying left-sided HF is unknown. The purpose of this study is to unearth significant modules, pivotal genes and candidate regulatory components governing the progression of left-sided HF by bioinformatical analysis. METHODS: A total of 319 samples in GSE57345 dataset were used for weighted gene correlation network analysis (WGCNA). ClusterProfiler package in R was used to conduct functional enrichment for genes uncovered from the modules of interest. Regulatory networks of genes were built using Cytoscape while Enrichr database was used for identification of transcription factors (TFs). The MCODE plugin was used for identifying hub genes in the modules of interest and their validation was performed based on GSE1869 dataset. RESULTS: A total of six significant modules were identified. Notably, the blue module was confirmed as the most crucially associated with left-sided HF, ischemic heart disease (ISCH) and dilated cardiomyopathy (CMP). Functional enrichment conveyed that genes belonging to this module were mainly those driving the extracellular matrix-associated processes such as extracellular matrix structural constituent and collagen binding. A total of seven transcriptional factors, including Suppressor of Zeste 12 Protein Homolog (SUZ12) and nuclear factor erythroid 2 like 2 (NFE2L2), adrenergic receptor (AR), were identified as possible regulators of coexpression genes identified in the blue module. A total of three key genes (OGN, HTRA1 and MXRA5) were retained after validation of their prognostic value in left-sided HF. The results of functional enrichment confirmed that these key genes were primarily involved in response to transforming growth factor beta and extracellular matrix. CONCLUSION: We uncovered a candidate gene signature correlated with HF, ISCH and CMP in the left ventricle, which may help provide better prognosis and therapeutic decisions and in HF, ISCH and CMP patients.

Warm-White-Light-Emitting Diode Based on a Dye-Loaded Metal-Organic Framework for Fast White-Light Communication.

A dye@metal-organic framework (MOF) hybrid was used as a fluorophore in a white-light-emitting diode (WLED) for fast visible-light communication (VLC). The white light was generated from a combination of blue emission of the 9,10-dibenzoate anthracene (DBA) linkers and yellow emission of the encapsulated Rhodamine B molecules. The MOF structure not only prevents dye molecules from aggregation-induced quenching but also efficiently transfers energy to the dye for dual emission. This light-emitting material shows emission lifetimes of 1.8 and 5.3 ns for the blue and yellow components, respectively, which are significantly shorter than the 200 ns lifetime of Y3Al5O12:Ce3+ in commercial WLEDs. The MOF-WLED device exhibited a modulating frequency of 3.6 MHz for VLC, six times that of commercial WLEDs.

Molecular mechanisms in microRNA-mediated TRB3 gene and hypertension left ventricular hypertrophy.

The present study investigated the relationship between microRNA-mediated TRB3 gene and hypertension left ventricular hypertrophy at the molecular level. Polymorphic site in TRB3 gene was identified by direct PCR method, and the correlation between the SNP site and ventricular hypertrophy was determined. MicroRNAs target gene sequence interacting on the TRB3 polymorphic site was screened by bioinformatics, and the effect of microRNAs on the TRB3 polymorphic site was finally verified by luciferase test. Two polymorphic sites rs6186912 and rs6186923 were found in the TRB3 gene, and the direct relationship between rs6186923 polymorphic site and the hypertension left ventricular hypertrophy in patients with myocardial hypertrophy was compared and analyzed. Pictar software was used to analyze the effect of miR-100 on rs6186923, and the argumentation was verified by luciferase test. In conclusion, the study showed that the TRB3 gene polymorphism rs6186923 was able to affect the TRB3 gene by affecting the binding of miR-100, which indirectly caused the formation of hypertension left ventricular hypertrophy.

Expression Changes of Long Noncoding RNA in the Process of Endothelial Cell Activation.

BACKGROUND: Endothelial cells have been shown to be in response to a variety of local and systemic stimuli, and are able to transition between quiescent and activated states. Endothelial cell activation is critical for the pathogenesis of various cardiovascular diseases. However, the expression changes of long non-coding RNAs (lncRNAs) are still unknown in the process of endothelial cell activation. Thus, this study was aimed to investigate expression changes of lncRNA before and after endothelial cell activation. MATERIALS AND METHODS: In an experimental model of peripheral venous congestion, endothelial cells were activated and analyzed with Affymetrix HG-U133 plus2.0 microarray. We analyzed these microarray data and reannotated the microarray probes for lncRNA. RESULTS: According to the definition of absolute fold change>2 and p value <0.05, 27 differentially expressed lncRNAs were identified and only 1 lncRNA transcript, ENST00000509256 was down-regualted. Co-expression network of lncRNA and mRNA were constructed to predict function of the dysregulated lncRNA. Gene set enrichment analyses suggested that these ENST00000509256 was associated with many important functions, such as cell-cell signaling and regulation of cell differentiation. CONCLUSION: Many lncRNAs are dysregulated upon endothelial cell activation and further experiments are needed to identify the potential biological functions of these lncRNAs.

Multiplicative interaction between mean corpuscular volume and red cell distribution width with target organ damage in hypertensive patients.

BACKGROUND: Accumulating evidence suggests that increased red cell distribution width (RDW) and mean corpuscular volume (MCV) were both poor prognostic factors for patients with cardiovascular diseases. Recently, the multiplicative interaction between RDW and MCV has been observed for predicting mortality in elderly patients without anemia; however, the relationship between the product of RDW-MCV and hypertension-induced target organ damage (TOD) has not been evaluated. METHODS: We performed a cross-sectional study in 1115 hypertensive patients. RDW and MCV were determined using automated hematology analyzers. Prevalence of TOD was evaluated by estimated glomerular filtration rate, carotid intima-media thickness, and left ventricular mass index. RESULTS: The prevalence of TOD was observed to be increased with the RDW or product of RDW-MCV quartiles. Moreover, RDW, MCV and product of RDW-MCV were significantly higher in patients with TOD compared to those without TOD. According to two logistic regression models, the associations of RDW and MCV with TOD were lost after adjustment for other factors. However, product of RDW-MCV remains an independent predictor of TOD, with per 0.4 fL increase in the product of RDW-MCV associated with a 16% increased risk of TOD (P=.012). CONCLUSIONS: The inclusion of MCV by calculating the product of RDW-MCV appears to enhance the association of RDW with TOD.

Target organ damage in primary hypertensive patients: role of the morning heart rate surge.

BACKGROUND: The morning heart rate surge (MHRS) and morning blood pressure surge (MBPS) may be responsible for the high prevalence of cardiovascular events during the morning period. The clinical significance of the MBPS has been well established, but that of the MHRS remains unclear. Thus, we evaluated the association between the MHRS and target organ damage (TOD). METHODS: A cross-sectional study of 580 hypertensive patients was performed. MHRS and heart rate variability (HRV) were analyzed by 24 h electrocardiogram. TOD was assessed by estimated glomerular filtration rate, carotid intima-media thickness (IMT), and left ventricular mass index. RESULTS: The prevalence of TOD tended to decrease with sleep-trough MHRS (first to fourth quartiles: 71%, 70.3%, 58.6%, and 52.7%, respectively) or prewaking MHRS quartiles (first to fourth quartiles: 65.3%, 73.6%, 61.4%, and 54.2%, respectively), whereas the opposite trend was observed for standard deviation of all normal NN intervals (SDNN). Moreover, sleep-trough MHRS, prewaking MHRS, SDNN, and SDNN index were significantly lower in patients with TOD than in those without TOD. According to four logistic regression models, the associations of prewaking MHRS, SDNN, and SDNN index with TOD were lost after adjustment for age and BP. Patients in the first (≤11.125 bpm) and second sleep-trough MHRS quartiles (11.125-15.75 bpm) had a 1.95-2.06-fold increased risk of TOD compared with those in the fourth quartile (p < 0.05). CONCLUSION: A blunted sleep-trough MHRS, which may serve as a surrogate marker for autonomic imbalance, was independently associated with TOD in primary hypertensive patients.

[Elastic registration method to compute deformation functions for mitral valve].

Mitral valve disease is one of the most popular heart valve diseases. Precise positioning and displaying of the valve characteristics is necessary for the minimally invasive mitral valve repairing procedures. This paper presents a multi-resolution elastic registration method to compute the deformation functions constructed from cubic B-splines in three dimensional ultrasound images, in which the objective functional to be optimized was generated by maximum likelihood method based on the probabilistic distribution of the ultrasound speckle noise. The algorithm was then applied to register the mitral valve voxels. Numerical results proved the effectiveness of the algorithm.

Therapeutic effects of neuregulin-1 in diabetic cardiomyopathy rats.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a disorder of the heart muscle in people with diabetes, which is characterized by both systolic and diastolic dysfunction. The effective treatment strategy for DCM has not been developed. METHODS: Rats were divided into 3 groups with different treatment. The control group was only injected with citrate buffer (n = 8). The diabetes group and diabetes treated group were injected with streptozotocin to induce diabetes. After success of diabetes induction, the rats with diabetes were treated with (diabetes treated group, n = 8) or without (diabetes group, n = 8) recombinant human Neuregulin-1 (rhNRG-1). All studies were carried out 16 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate the cardiac function. Apoptotic cells were determined by TUNEL staining. Left ventricular (LV) sections were stained with Masson to investigate myocardial collagen contents. Related gene expressions were analyzed by quantitative real-time PCR (qRT-PCR). RESULTS: Diabetes impaired cardiac function manifested by reduced LV systolic pressure (LVSP), maximum rate of LV pressure rise and fall (+dp/dt max and -dp/dt max) and increased LV end-diastolic pressure (LVEDP). The rhNRG-1 treatment could significantly alleviate these symptoms and improve heart function. More TUNEL staining positive cells were observed in the diabetic group than that in the control group, and the rhNRG-1 treatment decreased apoptotic cells number. Furthermore, qRT-PCR assay demonstrated that rhNRG-1 treatment could decrease the expression of bax and caspase-3 and increase that of bcl-2. Collagen volume fraction was higher in the diabetic group than in the control group. Fibrotic and fibrotic related mRNA (type I and type III collagen) levels in the myocardium were significantly reduced by administration of rhNRG-1. CONCLUSION: rhNRG-1 could significantly improve the heart function and reverse the cardiac remodeling of DCM rats with chronic heart failure. These results support the clinical possibility of applying rhNRG-1 as an optional therapeutic strategy for DCM treatment in the future.

[Role of liver X receptors on cardiomyocyte hypertrophy].

OBJECTIVE: To investigate the expression of liver X receptors (LXR) in hypertrophic myocardium and the effect of LXR agonist T0901317 on angiotensin II (AngII) induced cardiomyocyte hypertrophy. METHODS: Transverse aortic coarctation (TAC) or sham operation were performed in 2-month-old wide type mice (C57/B6). Two weeks later, the expression of LXR in myocardium was detected by quantitative real-time PCR analysis and Western blot analysis. The effect of LXR agonist T0901317 on AngII-induced hypertrophy in cultured neonatal rat cardiomyocytes was also assessed. RESULTS: Quantitative real-time PCR analysis and Western blot analysis showed that LXRalpha but not LXRbeta expression was upregulated post TAC both at mRNA and protein levels (All P < 0.05). AngII induced increased [(3)H] leucine incorporation and cardiomyocyte hypertrophy were significantly reduced by T0901317 in a dose-dependent manner (P < 0.05). T0901317 also dose-dependently inhibited atrial natriuretic peptide (ANP) gene expression in cardiomyocytes (P < 0.05). CONCLUSION: Our findings strongly suggest that LXR is a potent mediator of cardiomyocyte hypertrophy and LXR activation could attenuate AngII induced cardiomyocyte hypertrophy in vitro.