Low alpha-defensin gene copy number increases the risk for IgA nephropathy and renal dysfunction

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Although a major source of genetic variation, copy number variations (CNVs) and their involvement in disease development have not been well studied. Here, we performed association analysis of the DEFA1A3 CNV locus in two independent IgAN cohorts of Southern Chinese Han (total1189 cases and 1187 controls). We discovered three independent copy number associations within the locus: DEFA1A3 (P=3.99×10-9, OR=0.88), DEFA3 (P=6.55×10-5, OR=0.82) and a noncoding deletion variant (211bp) (P=3.50×10-16, OR=0.75) (OR per copy, fixed-effects meta-analysis). While showing strong association with increased risk for IgAN (P=9.56×10-20), low total copy numbers of the three variants also showed significant association with renal dysfunction in patients with IgAN (P=0.03, HR=3.69, after controlling for the effects of known prognostic factors) as well as high serum IgA1 (P=0.02) and a high proportion of galactose-deficient IgA1 (P=0.03). For replication, we confirmed the associations of DEFA1A3 (P=4.42×10-4, OR=0.82) and DEFA3 copy numbers (P=4.30×10-3, OR=0.74) with IgAN in a Caucasian cohort (531 cases and 198 controls) and found the 211bp variant to be much rarer in Caucasians. Interestingly, we also observed an association of the 211bp copy number with membranous nephropathy (P=1.11×10-7, OR=0.74 in 493 Chinese cases and 500 matched controls), but not with diabetic kidney disease (in 806 Chinese cases and 786 matched controls). By explaining 4.96% of disease risk and influencing the renal dysfunction in IgAN, the DEFA1A3 CNV locus is a potential candidate for therapeutic target and prognostic marker development

Insight-HXMT observations of Swift J0243.6+6124 during its 2017-2018 outburst

The recently discovered neutron star transient Swift J0243.6+6124 has been monitored by {\it the Hard X-ray Modulation Telescope} ({\it Insight-\rm HXMT). Based on the obtained data, we investigate the broadband spectrum of the source throughout the outburst. We estimate the broadband flux of the source and search for possible cyclotron line in the broadband spectrum. No evidence of line-like features is, however, found up to $\rm 150~keV$. In the absence of any cyclotron line in its energy spectrum, we estimate the magnetic field of the source based on the observed spin evolution of the neutron star by applying two accretion torque models. In both cases, we get consistent results with $B\rm \sim 10^{13}~G$, $D\rm \sim 6~kpc$ and peak luminosity of $\rm >10^{39}~erg~s^{-1}$ which makes the source the first Galactic ultraluminous X-ray source hosting a neutron star.Comment: publishe

Overview to the Hard X-ray Modulation Telescope (Insight-HXMT) Satellite

As China's first X-ray astronomical satellite, the Hard X-ray Modulation Telescope (HXMT), which was dubbed as Insight-HXMT after the launch on June 15, 2017, is a wide-band (1-250 keV) slat-collimator-based X-ray astronomy satellite with the capability of all-sky monitoring in 0.2-3 MeV. It was designed to perform pointing, scanning and gamma-ray burst (GRB) observations and, based on the Direct Demodulation Method (DDM), the image of the scanned sky region can be reconstructed. Here we give an overview of the mission and its progresses, including payload, core sciences, ground calibration/facility, ground segment, data archive, software, in-orbit performance, calibration, background model, observations and some preliminary results.Comment: 29 pages, 40 figures, 6 tables, to appear in Sci. China-Phys. Mech. Astron. arXiv admin note: text overlap with arXiv:1910.0443

Cooling Effect of Water Injection on a High-Temperature Supersonic Jet

The high temperature and high pressure supersonic jet is one of the key problems in the design of solid rocket motors. To reduce the jet temperature and noise, cooling water is typically injected into the exhaust plume. Numerical simulations for the gas-liquid multiphase flow field with mixture multiphase model were developed and a series of experiments were carried out. By introducing the energy source terms caused by the vaporization of liquid water into the energy equation, a coupling solution was developed to calculate the multiphase flow field. The temperature data predictions agreed well with the experimental results. When water was injected into the plume, the high temperature core region area was reduced, and the temperature on the head face was much lower than that without water. The relationship between the reduction of temperature on the bottom plate and the momentum ratio is developed, which can be used to predict the cooling effect of water injection in many cases

Upregulated Expression of Intestinal Antimicrobial Peptide HD5 Associated with Renal Function in IgA Nephropathy

Purpose. It was reported that gut-kidney axis may play an important role in IgA nephropathy (IgAN). Previous five GWASs of different populations for IgAN have discovered several genes related to intestinal immunity, including DEFA gene. However, the roles of the encoded proteins of DEFA5/6 which were called intestinal antimicrobial peptides HD5 and HD6 were not clear in kidney disease, such as IgAN. The purpose of this study was to clarify the association of HD5 and HD6 with IgAN. Methods. We measured HD5 and HD6 in serum, urine, and kidney of IgAN patients and normal controls by ELISA, Western blot, and immunofluorescence. The association of HD5 or HD6 levels with clinical and pathologic phenotypes was analyzed. Results. Serum levels of HD5 and HD6 were significantly higher in IgAN patients than those in normal controls. Baseline serum HD5 levels were significantly associated with eGFR (P=0.002) and tubular atrophy/interstitial fibrosis (P=0.004) by stepwise multivariate regression analysis. Compared to the patients with serum HD5 below the median level, patients with elevated serum HD5 above the median level had a significantly worse renal outcome (log-rank test, P=0.009) by Kaplan-Meier analysis. A Cox regression model showed that serum HD5 was an independent prognostic factor (HR=1.239, P=0.029) after adjusting for the well-known predictors of outcome in IgAN patients. In renal biopsies of IgAN patients, HD5 was significantly expressed in the damaged proximal tubules, while no immunoreactive HD6 was found. Interestingly, the serum HD6 level of IgAN patients was significantly associated with gender. Conclusions. In IgAN patients, an elevated serum HD5 level at the time of renal biopsy was associated with poor renal outcomes. HD5 rather than HD6 was probably associated with renal function of IgAN patients

Additional file 2 of Identification of novel cell-free RNAs in maternal plasma as preterm biomarkers in combination with placental RNA profiles

Additional file 2: Functional annotation of hub genes in plasma and placental group

Additional file 1 of Identification of novel cell-free RNAs in maternal plasma as preterm biomarkers in combination with placental RNA profiles

Additional file 1: Table S1. Maternal characteristics of participants in this study involved in RT-qPCR. Table S2. Gene primer sequences used in RT-qPCR. Figure S1. Principal component analysis (PCA) for sample clustering using RNA-seq data. Figure S2. Comparison of plasma and placental transcriptome analysis. Figure S3. Complexity of RNA regulatory molecules biotype. Figure S4. Construction of the PPI network. Figure S5. The key genes in plasma and placental PPI network. Figure S6. Comparison of the relative expression levels of ARHGEF28. Figure S7. Predictive models for preterm birth combined with clinical factors. Figure S8. The exploration of relatedness between clinical factors for preterm birth and the expression level of ARHGEF28. Figure S9. The exploration of relatedness between clinical factors for preterm birth and gestational age