Serum miR-195-5p Exhibits Clinical Significance in the Diagnosis of Essential Hypertension with Type 2 Diabetes Mellitus by Targeting DRD1

OBJECTIVES: Diagnosis and management of essential hypertension (EH) or type 2 diabetes mellitus (T2DM) by combining comprehensive treatment and classificatory diagnosis have been continuously improved. However, understanding the pathogenesis of EH patients with concomitant T2DM and subsequent treatment remain the major challenges owing to the lack of non-invasive biomarkers and information regarding the underlying mechanisms. METHODS: Herein, we collected 200 serum samples from EH and/or T2DM patients and healthy donors (N). Gene-expression profiling was conducted to identify candidate microRNAs with clinical significance. Then, a larger cohort of the aforementioned patients and 50 N were used to identify the correlation between the tumor suppressor miR-195-5p and EH and/or T2DM. The dual-luciferase reporter assay was used to explore the target genes of miR-195-5p. The suppressive effects of miR-195-5p on the 3′-UTR of the dopamine receptor D1 (DRD1) transcript in EH patients with concomitant T2DM were verified as well. RESULTS: Compared with that in other groups, serum miR-195-5p was highly downregulated in EH patients with concomitant T2DM. miR-195-5p overexpression efficiently suppressed DRD1 expression by binding to the two 3′-UTRs. Additionally, two single nucleotide polymorphisms, including 231T-A and 233C-G, in the miR-195-5p binding sites of the DRD1 3′-UTR were further identified. Collectively, we identified the potential clinical significance of DRD1 regulation by miR-195-5p in EH patients with concomitant T2DM. CONCLUSIONS: Our data suggested that miR-195-5p circulating in the peripheral blood served as a novel biomarker and therapeutic target for EH and T2DM, which could eventually help address major challenges during the diagnosis and treatment of EH and T2DM

Multiple organ infection and the pathogenesis of SARS

After >8,000 infections and >700 deaths worldwide, the pathogenesis of the new infectious disease, severe acute respiratory syndrome (SARS), remains poorly understood. We investigated 18 autopsies of patients who had suspected SARS; 8 cases were confirmed as SARS. We evaluated white blood cells from 22 confirmed SARS patients at various stages of the disease. T lymphocyte counts in 65 confirmed and 35 misdiagnosed SARS cases also were analyzed retrospectively. SARS viral particles and genomic sequence were detected in a large number of circulating lymphocytes, monocytes, and lymphoid tissues, as well as in the epithelial cells of the respiratory tract, the mucosa of the intestine, the epithelium of the renal distal tubules, the neurons of the brain, and macrophages in different organs. SARS virus seemed to be capable of infecting multiple cell types in several organs; immune cells and pulmonary epithelium were identified as the main sites of injury. A comprehensive theory of pathogenesis is proposed for SARS with immune and lung damage as key features

Searching for Black Hole Candidates by LAMOST and ASAS-SN

Most dynamically confirmed stellar-mass black holes (BHs) and their candidates were originally selected from X-ray outbursts. In the present work, we search for BH candidates in the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) survey using the spectra along with photometry from the All Sky Automated Survey for SuperNovae (ASAS-SN), where the orbital period of the binary may be revealed by the periodic light curve, such as the ellipsoidal modulation type. Our sample consists of nine binaries, where each source contains a giant star with large radial velocity variation (ΔV_R ≳ 70 km s^(-1)) and periods known from light curves. We focus on the nine sources with long periods (T_(ph) > 5 days) and evaluate the mass M_2 of the optically invisible companion. Since the observed ΔV_R from only a few repeating spectroscopic observations is a lower limit of the real amplitude, the real mass M_2 can be significantly higher than the current evaluation. It is likely an efficient method to place constraints on M 2 by combining ΔV_R from LAMOST and T_(ph) from ASAS-SN, particularly by the ongoing LAMOST Medium Resolution Survey

FGF18 Enhances Migration and the Epithelial-Mesenchymal Transition in Breast Cancer by Regulating Akt/GSK3β/Β-Catenin Signaling

Background/Aims: Fibroblast growth factors (FGFs) and their high-affinity receptors contribute to autocrine and paracrine growth stimulation in several human malignant tumors, including breast cancer. However, the mechanisms underlying the carcinogenic actions of FGF18 remain unclear. Methods: The transcription level of FGF18 under the hypoxic condition was detected with quantitative PCR (qPCR). A wound-healing assay was performed to assess the role of FGF18 in cell migration. A clonogenicity assay was used to determine whether FGF18 silencing affected cell clonogenicity. Western blotting was performed to investigate Akt/GSK3β/β-catenin pathway protein expression. Binding of β-catenin to the target gene promoter was determined by chromatin immunoprecipitation (ChIP) assays. Results: FGF18 promoted the epithelial-mesenchymal transition (EMT) and migration in breast cancer cells through activation of the Akt/GSK3β/β-catenin pathway. FGF18 increased Akt-Ser473 and -Thr308 phosphorylation, as well as that of GSK3β-Ser9. FGF18 also enhanced the transcription of proliferation-related genes (CDK2, CCND2, Ki67), metastasis-related genes (TGF-β, MMP-2, MMP-9), and EMT markers (Snail-1, Snail-2, N-cadherin, vimentin, TIMP1). β-catenin bound to the target gene promoter on the ChIP assay. Conclusion: FGF18 contributes to the migration and EMT of breast cancer cells following activation of the Akt/GSK3β/β-catenin pathway. FGF18 expression may be a potential prognostic therapeutic marker for breast cancer

Proton-Boron Fusion Yield Increased by Orders of Magnitude with Foam Targets

A novel intense beam-driven scheme for high yield of the tri-alpha reaction 11B(p,{\alpha})2{\alpha} was investigated. We used a foam target made of cellulose triacetate (TAC, C_9H_{16}O_8) doped with boron. It was then heated volumetrically by soft X-ray radiation from a laser heated hohlraum and turned into a homogenous, and long living plasma. We employed a picosecond laser pulse to generate a high-intensity energetic proton beam via the well-known Target Normal Sheath Acceleration (TNSA) mechanism. We observed up to 10^{10}/sr {\alpha} particles per laser shot. This constitutes presently the highest yield value normalized to the laser energy on target. The measured fusion yield per proton exceeds the classical expectation of beam-target reactions by up to four orders of magnitude under high proton intensities. This enhancement is attributed to the strong electric fields and nonequilibrium thermonuclear fusion reactions as a result of the new method. Our approach shows opportunities to pursue ignition of aneutronic fusion

Mapping a Partial Andromonoecy Locus in Citrullus lanatus Using BSA-Seq and GWAS Approaches

[EN] The sexual expression of watermelon plants is the result of the distribution and occurrence of male, female, bisexual and hermaphrodite flowers on the main and secondary stems. Plants can be monoecious (producing male and female flowers), andromonoecious (producing male and hermaphrodite flowers), or partially andromonoecious (producing male, female, bisexual, and hermaphrodite flowers) within the same plant. Sex determination of individual floral buds and the distribution of the different flower types on the plant, are both controlled by ethylene. A single missense mutation in the ethylene biosynthesis geneCitACS4, is able to promote the conversion of female into hermaphrodite flowers, and therefore of monoecy (genotypeMM) into partial andromonoecy (genotypeMm) or andromonoecy (genotypemm). We phenotyped and genotyped, for theM/mlocus, a panel of 207 C. lanatusaccessions, including five inbreds and hybrids, and found several accessions that were repeatedly phenotyped as PA (partially andromonoecious) in several locations and different years, despite beingMM. A cosegregation analysis between a SNV inCitACS4and the PA phenotype, demonstrated that the occurrence of bisexual and hermaphrodite flowers in a PA line is not dependent onCitACS4, but conferred by an unlinked recessive gene which we calledpa. Two different approaches were performed to map thepagene in the genome ofC. lanatus: bulk segregant analysis sequencing (BSA-seq) and genome wide association analysis studies (GWAS). The BSA-seq study was performed using two contrasting bulks, the monoecious M-bulk and the partially andromonoecious PA-bulk, each one generated by pooling DNA from 20 F2 plants. For GWAS, 122 accessions from USDA gene bank, already re-sequenced by genotyping by sequencing (GBS), were used. The combination of the two approaches indicates thatpamaps onto a genomic region expanding across 32.24-36.44 Mb in chromosome 1 of watermelon. Fine mapping narrowed down thepalocus to a 867 Kb genomic region containing 101 genes. A number of candidate genes were selected, not only for their function in ethylene biosynthesis and signalling as well as their role in flower development and sex determination, but also by the impact of the SNPs and indels differentially detected in the two sequenced bulks.This work has been funded by grant UAL18-BIO-B017-B, awarded by the call "Proyectos UAL-FEDER " within the framework of the 2014-2020 FEDER-Andalusia Operational Program, as well as by the research group BIO293 of the University of Almeria.Aguado, E.; García, A.; Iglesias-Moya, J.; Romero, J.; Wehner, TC.; Gómez-Guillamón, ML.; Picó Sirvent, MB.... (2020). Mapping a Partial Andromonoecy Locus in Citrullus lanatus Using BSA-Seq and GWAS Approaches. 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Searching for Black Hole Candidates by LAMOST and ASAS-SN

Most dynamically confirmed stellar-mass black holes (BHs) and their candidates were originally selected from X-ray outbursts. In the present work, we search for BH candidates in the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) survey using the spectra along with photometry from the All Sky Automated Survey for SuperNovae (ASAS-SN), where the orbital period of the binary may be revealed by the periodic light curve, such as the ellipsoidal modulation type. Our sample consists of nine binaries, where each source contains a giant star with large radial velocity variation (ΔV_R ≳ 70 km s^(-1)) and periods known from light curves. We focus on the nine sources with long periods (T_(ph) > 5 days) and evaluate the mass M_2 of the optically invisible companion. Since the observed ΔV_R from only a few repeating spectroscopic observations is a lower limit of the real amplitude, the real mass M_2 can be significantly higher than the current evaluation. It is likely an efficient method to place constraints on M 2 by combining ΔV_R from LAMOST and T_(ph) from ASAS-SN, particularly by the ongoing LAMOST Medium Resolution Survey