Disorders mainly caused by ischemia‐reperfusion (I/R), including stroke and myocardial infarction, is linked to debilitating health conditions and death. Recent research indicates that microRNAs ...(miRNAs) mediate the process of ischemic pathology. This study investigated the effects of miR‐145‐5p in regulating myocardial ischemic injury. The I/R models were established in rat cardiomyocytes H9C2 and rats. Western blot analysis and quantitative polymerase chain reaction was performed to analyze protein expression. Annexin V‐FITC/PI staining was conducted to evaluate cell apoptosis. The application of miR‐145‐5p mimics and inhibitor revealed that miR‐145‐5p promoted apoptosis in cardiomyocytes. Furthermore, we found that miR‐145‐5p directly inhibited dual specificity phosphatase 6 (DUSP6) by luciferase reporter assay. The results indicated that DUSP6 was beneficial against I/R injury through inhibiting c‐Jun N‐terminal kinase pathways. In conclusion, the essential roles of miR‐145‐5p and DUSP6 in I/R provide a novel therapeutic target to develop future intervention strategies.
miR‐145‐5p negatively regulated dual specificity phosphatase 6 (DUSP6) expression after ischemia‐reperfusion (I/R) both in vitro and in vivo, and further activated mitogen‐activated protein kinases signaling for apoptosis. Inhibiting miR‐145‐5p actions can have protective effects after I/R in cardiomyocytes.
Flowering is a critical agricultural trait that substantially affects tomato fruit yield. Although drought stress influences flowering time, the molecular mechanism underlying drought-regulated ...flowering in tomato remains elusive. In this study, we demonstrated that loss of function of tomato OPEN STOMATA 1 (SlOST1), a protein kinase essential for abscisic acid (ABA) signaling and abiotic stress responses, lowers the tolerance of tomato plants to drought stress. slost1 mutants also exhibited a late flowering phenotype under both normal and drought stress conditions. We also established that SlOST1 directly interacts with and phosphorylates the NAC (NAM, ATAF and CUC)-type transcription factor VASCULAR PLANT ONE-ZINC FINGER 1 (SlVOZ1), at residue serine 67, thereby enhancing its stability and nuclear translocation in an ABA-dependent manner. Moreover, we uncovered several SlVOZ1 binding motifs from DNA affinity purification sequencing analyses and revealed that SlVOZ1 can directly bind to the promoter of the major flowering-integrator gene SINGLE FLOWER TRUSS to promote tomato flowering transition in response to drought. Collectively, our data uncover the essential role of the SlOST1-SlVOZ1 module in regulating flowering in response to drought stress in tomato and offer insights into a novel strategy to balance drought stress response and flowering.
Ovarian carcinoma is a lethal gynecological malignancy. Women with ovarian cancer (OC) are highly recurrent and typically diagnosed at late stage. Ten-eleven translocation protein 3 (TET3) belongs to ...the family of ten-eleven translocations (TETs) which induce DNA demethylation and gene regulation in epigenetic level by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Previous studies indicated that TET3 is overexpressed in ovarian cancer tissues. However, the clinic-pathological functions and prognostic values of TET3 remain unclear. Here we performed an integrative study to identify the role of TET3 by bioinformatics analysis. The TET3 expression in ovarian cancer was assessed with Oncomine database, and validated with TCGA and GTEx database. The correlation of TET3 gene alteration and clinic-pathological functions was addressed by integrative analysis of GEO datasets. Then we showed mainly TET3 gain and diploid but less deletion in ovarian cancer by copy number alteration (CNA) or mutation analysis with cBioPortal. Furthermore, by using Kaplan-Meier plotter (K-M plotter), we evaluated that high TET3 level was associated with poor survival in ovarian cancer patients, which was validated with analysis by PrognoScan database and gene differential analyses with TCGA and GTEx. This is the first study demonstrated that elevated expression of TET3 is associated with poor clinic-pathological functions, poor prognosis, wherein TET3, which presents epigenetic changes or methylation changes, might be served as a diagnostic marker or therapeutic target for ovarian cancer.
The polyplexes which are formed between cationic polymers and DNA through electrostatic interactions and thus known as polycation/DNA complexes, are by far the most widely used non-viral gene ...delivery vectors. Many factors such as molecular weight, surface charge, charge density, hydrophilicity and the structure of cationic polymers affect gene transfection efficiency of cationic polymers. Therefore, optimization of cationic polymers is necessary to improve the gene transfection efficiency. Currently several important cationic polymers were used as cationic vectors for gene delivery which included PEI, PLL, Chitosan and PAMAM. Their most advantages and the rational design are introduced in this article. However, these systems are much less efficient in gene transfer experiments compared with viral systems. Some strategies such as PEGylation, combination and multifunctional modification were developed in the cationic polymeric vectors for gene delivery. Hereby, this article will review various kinds of copolymers with higher stability but biodegradable, bioresponsive and easy refined molecular weight which could be easily modification. Especially, the multifunctional modified polyplexes and polymersomes will be further discussion due to their ability to conjugate biologically active ligands, which can be used as potential nanostructured biomaterials for future in vivo gene delivery.
Mono- and multi-layered molybdenum disulfide (MoS2) is considered to be one of the next generation anode materials for rechargeable ion batteries. Structural transformation from trigonal prismatic ...(2H) to octahedral (1T) upon lithium or sodium intercalation has been in-situ observed experimentally using transmission electron microscope during studies of their electrochemical dynamics processes. In this work, we explored the fundamental mechanisms of this structural transformation in both mono- and bi-layered MoS2 using density functional theory. For the intercalated MoS2, the Li and Na donate their electrons to the MoS2. Based on the theoretical analysis, we confirmed that, for the first time, electron transfer is dominant in initiating this structural transformation, and the results provide an in-depth understanding of the transformation mechanism induced by the electron doping. The critical values of electron concentrations for this structural transformation are decreased with increasing the layer thickness.
In this letter, we consider secure transmissions of millimeter wave simultaneous wireless information and power transfer unmanned aerial vehicle (UAV) relay networks, where a source transmits ...confidential information to an energy-constrained destination on the ground with the help of a UAV-based relay in the presence of multiple independent homogeneous Poisson point process eavesdroppers. First, we derive closed-form expression of the lower bound of average secrecy rate using 3-D antenna gain model. Then, we study the secrecy rate lower bound maximization problem by optimizing the source/UAV transmit power, power splitting ratio, and UAV's location. To solve this non-convex problem, we propose an alternate optimization algorithm by solving three sub-problems iteratively. Simulation results show that the proposed algorithm can greatly improve the average secrecy rate.
Chlorella vulgaris was cultivated in different proportions of activated sludge extracts, which was from the treatment of synthetic wastewater containing tetrachlorophenol. The growth period of C. ...vulgaris could be shortened for about 10 days when sludge extract was mixed into BG11 culture substrate, and the growth of C. vulgaris was promoted during the period of adaptation and logarithmic period. In the stable and decay period, when the proportion of sludge extract increased to 50%, cell proliferation was inhibited. There was an evident positive correlation between the total and average amount of starch polysaccharide with sludge concentration. When C. vulgaris was cultivated with pure sludge extracts, the total amount of starch and polysaccharide was up to 103 and 125 mg/L. Therefore, the low-toxic sludge extracts were more beneficial to the accumulation of carbohydrates. In the 100% sludge extracts culture medium, chlorophyll-a in C. vulgaris was accumulated to 30.2 mg/L on the 25th day. Through the analysis of algal cells' ultrastructures, it was shown that the photosynthesis was strengthened greatly with low-toxic sludge extracts. The results show that the rich heterotrophic carbon source in the sludge extract can be used as an excellent medium for Chlorella. It provides new ideas for the harmless utilization of surplus sludge as a resource. At the same time, the use of nutrients in the sludge extract to cultivate Chlorella is of great significance to low-cost algae cultivation.
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Transformation from linear to branched wormlike micelle generally results in the dramatic loss of viscoelasticity. In this study, adopting Coarse-grained molecular dynamics ...simulation, the conformational transformation was studied in a binary system of cetyltrimethylammonium chloride (CTAC) and sodium salicylate (Nasal). A gross conformation diagram of micelle at different CTAC concentrations and molar ratios of CTAC/Nasal indicates that the branched structure could form at zeta potential lower than 32mV. Further, the dynamic process displays that four sequential stages, approaching, forming salt bridge, yielding stalk, and coalescing together, involve in this transformation. And a fascinating process, an organic salt bridge first form between two approaching micelles and then induces the surfactant jump out to form stalk, was observed. In addition, some rational strategies were proposed to reduce the probability of this conformational transformation. Our study provides a molecular-level understanding of transformation behaviour from linear to branched wormlike micelles.
Homocysteine can accelerate the senescence of endothelial progenitor cells or endothelial cells (ECs) via telomerase inactivation and length shortening. However, the underlying mechanism is unclear. ...Here, we investigated whether homocysteine promotes endothelial senescence by reducing the expression and activity of human telomerase reverse transcriptase (hTERT) by DNA methylation to reduce ECs telomerase activity.
When compared with primary human umbilical vein endothelial cells grown under standard conditions, ECs with chronic homocysteine treatment showed accelerated upregulation of p16, p21, and p53, markers of cellular senescence, during 6 to 10 passages. Interestingly, homocysteine-stimulated but not angiotensin II-stimulated ECs senescence could be reversed by hypermethylation induced by folic acid or s-adenosylmethionine supplementation. Meanwhile, homocysteine promoted the shortening of telomere length specifically related to restoration of hTERT transcriptional expression and CCCTC-binding factor binding sites with hTERT promoter hypomethylation, as detected by quantitative real-time polymerase chain reaction, Western blot, methylation-specific polymerase chain reaction, and bisulfite sequencing assay. Electrophoretic mobility shift assay and chromatin immunoprecipitation results showed that homocysteine-reduced telomere activity and homocysteine-induced EC senescence might contribute to hTERT promoter demethylation by increasing CCCTC-binding factor repression and interfering in the SP1 binding to the demethylated hTERT promoter, which might relate with reduced of DNA methyltransferase 1. Furthermore, the CCCTC-binding factor-dependent mechanism of homocysteine-reduced hTERT expression via DNA demethylation was confirmed in aortic endothelia of mice with hyperhomocysteine levels.
CCCTC-binding factor and SP1 cross talk may contribute to homocysteine-reduced hTERT DNA methylation and expression in endothelial senescence.
Oxidized phospholipids (OxPLs), which arise due to oxidative stress, are proinflammatory and proatherogenic, but their roles in non-alcoholic steatohepatitis (NASH) are unknown. Here, we show that ...OxPLs accumulate in human and mouse NASH. Using a transgenic mouse that expresses a functional single-chain variable fragment of E06, a natural antibody that neutralizes OxPLs, we demonstrate the causal role of OxPLs in NASH. Targeting OxPLs in hyperlipidemic Ldlr−/− mice improved multiple aspects of NASH, including steatosis, inflammation, fibrosis, hepatocyte death, and progression to hepatocellular carcinoma. Mechanistically, we found that OxPLs promote ROS accumulation to induce mitochondrial dysfunction in hepatocytes. Neutralizing OxPLs in AMLN-diet-fed Ldlr−/− mice reduced oxidative stress, improved hepatic and adipose-tissue mitochondrial function, and fatty-acid oxidation. These results suggest targeting OxPLs may be an effective therapeutic strategy for NASH.
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•Oxidized phospholipids (OxPLs) accumulate in non-alcoholic steatohepatitis (NASH)•OxPLs induce oxidative stress and mitochondrial damage, in part by modifying MnSOD•Neutralizing OxPLs improved mitochondrial function and biogenesis in NASH•Neutralizing OxPLs ameliorates NASH
Oxidized phospholipids (OxPLs) accumulate in murine and human NASH, promoting oxidative stress, mitochondrial damage, and fibrosis. Antibody-mediated neutralization of OxPLs ameliorates murine NASH and the progression to hepatocellular carcinoma (HCC), suggesting this avenue as a potential therapeutic target for NASH.
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