A Mendelian randomization study to assess the genetic liability of type 1 diabetes mellitus for IgA nephropathy

BackgroundThe prevalence of immunoglobulin A nephropathy (IgAN) seems to be higher in patients with type 1 diabetes mellitus (T1DM) than that in the general population. However, whether there exists a causal relationship between T1DM and IgAN remains unknown.MethodsThis study conducted a standard two-sample Mendelian randomization (MR) analysis to assess the causal inference by four MR methods, and the inverse variance-weighted (IVW) approach was selected as the primary method. To further test the independent causal effect of T1DM on IgAN, multivariable MR (MVMR) analysis was undertaken. Sensitivity analyses incorporating multiple complementary MR methods were applied to evaluate how strong the association was and identify potential pleiotropy.ResultsMR analyses utilized 81 single-nucleotide polymorphisms (SNPs) for T1DM. The evidence supports a significant causal relationship between T1DM and increased risk of IgAN [odds ratio (OR): 1.39, 95% confidence interval (CI): 1.10–1.74 for IVW, p < 0.05]. The association still exists after adjusting for triglyceride (TG), fasting insulin (FI), fasting blood glucose (FBG), homeostasis model assessment of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR), and glycated hemoglobin (HbA1c). MVMR analysis indicated that the effect of T1DM on IgAN vanished upon accounting for low-density lipoprotein cholesterol (LDL-c; OR: 0.97, 95% CI: 0.90–1.05, p > 0.05).ConclusionsThis MR study provided evidence that T1DM may be a risk factor for the onset of IgAN, which might be driven by LDL-c. Lipid-lowering strategies targeting LDL-c should be enhanced in patients with T1DM to prevent IgAN

An N-terminal splice variant of human Stat5a that interacts with different transcription factors is the dominant form expressed in invasive ductal carcinoma

AbstractWe have identified a new variant of human Stat5a, found at higher ratios to full-length Stat5a in invasive ductal carcinoma versus contiguous normal tissue. The variant, missing exon 5, inhibits p21 and Bax production and increases cell number. After prolactin stimulation, only full-length Stat5a interacts with the vitamin D and retinoid X receptors, whereas only Δ5 Stat5a interacts with activating protein 1–2 and specificity protein 1. Prolactin also oppositely regulates interaction of the two Stat5a forms with β-catenin. We propose that a change in splicing leading to upregulation of this new isoform is a pathogenic aspect of invasive ductal carcinoma

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

DataSheet_1_A Mendelian randomization study to assess the genetic liability of type 1 diabetes mellitus for IgA nephropathy.docx

BackgroundThe prevalence of immunoglobulin A nephropathy (IgAN) seems to be higher in patients with type 1 diabetes mellitus (T1DM) than that in the general population. However, whether there exists a causal relationship between T1DM and IgAN remains unknown.MethodsThis study conducted a standard two-sample Mendelian randomization (MR) analysis to assess the causal inference by four MR methods, and the inverse variance-weighted (IVW) approach was selected as the primary method. To further test the independent causal effect of T1DM on IgAN, multivariable MR (MVMR) analysis was undertaken. Sensitivity analyses incorporating multiple complementary MR methods were applied to evaluate how strong the association was and identify potential pleiotropy.ResultsMR analyses utilized 81 single-nucleotide polymorphisms (SNPs) for T1DM. The evidence supports a significant causal relationship between T1DM and increased risk of IgAN [odds ratio (OR): 1.39, 95% confidence interval (CI): 1.10–1.74 for IVW, p 0.05).ConclusionsThis MR study provided evidence that T1DM may be a risk factor for the onset of IgAN, which might be driven by LDL-c. Lipid-lowering strategies targeting LDL-c should be enhanced in patients with T1DM to prevent IgAN.</p

A Traceable Online Will System Based on Blockchain and Smart Contract Technology

In recent years, with the rapid levels of economic development, there have been more and more problems in property inheritance and distribution. In today’s society, people still have many taboos when writing a will. Writing a will not only involves various laws and regulations but also costs a lot of money and time, which can be daunting. However, with the development of the Internet, blockchain technology has gradually been applied to many applications. Blockchain technology uses consensus algorithms to ensure consistency and records transaction information in blocks to ensure the effectiveness of transactions. In this paper, we use the cryptography mechanism to propose an online will system based on blockchain and smart contract technology. The architecture considers effectiveness and cost reduction. By combining this with blockchain technology, will assets are saved in blocks, which provides comprehensive will security and non-tamperable security protection. In addition, combined with a smart contract, it realizes the method of automatic property distribution. At the same time, this mechanism also proposes an arbitration solution when there are disputes over wills, and ensures the integrity of data, public verifiability, unforgeability, nonrepudiation, irreversibility of information, and the ability to resist counterfeiting attacks

Effects of freeze-thaw cycles on the size distribution and stability of soil aggregate in the permafrost regions of the Qinghai-Tibetan Plateau

As the basic units of soil structure, soil aggregate is essential for maintaining soil stability. Intensified freeze–thaw cycles have deeply affected the size distribution and stability of aggregate under global warming. To date, it is still lacking about the effects of freeze–thaw cycles on aggregate in the permafrost regions of the Qinghai-Tibetan Plateau (QTP). Therefore, we investigated the effects of diurnal and seasonal freeze–thaw processes on soil aggregate. Our results showed that the durations of thawing and freezing periods in the 0–10 cm layer were longer than in the 10–20 cm layer, while the opposite results were observed during completely thawed and frozen periods. Freeze–thaw strength was greater in the 0–10 cm layer than that in the 10–20 cm layer. The diurnal freeze–thaw cycles have no significant effect on the size distribution and stability of aggregate. However, 0.25 mm) and reduced aggregate stability. Our study has scientific guidance for evaluating the effects of freeze–thaw cycles on soil steucture and provides a theoretical basis for further exploration on soil and water conservation in the permafrost regions of the QTP

Preparation, structural diversity and characterization of a family of Cd(ii)–organic frameworks

Two Cd(ii)-organic frameworks based on 5-iodoisophthalate (IIP 2-), {[Cd(IIP)(bte)(H2O)]·H2O} n (1) and [Cd(IIP)(bpp)(H2O)]n (2), were obtained either at an ambient temperature or under solvothermal conditions at 120°C in the presence of 1,4-bis(1,2,4-triazol-1-yl)ethane (bte) and 1,3-bis(4-pyridyl)propane (bpp) as auxiliary ligands, respectively. 1 is a novel discrete single-walled Cd(ii)-organic tube (SWCOT) which further extends into a 3D supramolecular interdigitated microporous columnar architecture supported by C-I⋯I halogen bonds and hydrogen bonds, while 2 exhibits an interesting two-fold interpenetrated 3D diamond network architecture. When the auxiliary ligands bte or bpp were replaced by a longer spacer ligand with more flexibility, 1,4-bis(triazol-1-ylmethyl)benzene (bbtz), the unique discrete single-walled Cd(ii)-organic nanotube (SWCONT), {[Cd(IIP)(bbtz)(H 2O)]·H2O}n (3), which further extends into a 3D supramolecular microporous framework supported by face-to-face π⋯π stacking interactions and hydrogen bonds, was generated at room temperature. Under solvothermal conditions at 120°C, an interesting two-fold 2D "embracing" (4,4) topological network, [Cd(IIP)(bbtz)(H2O)] (4), which further extends into a two-fold 3D "embracing" supramolecular framework through O-H⋯O hydrogen bonds, is obtained. 4 loses crystallinity in air, leading to the formation of [Cd(IIP)(bbtz)]·0.5H2O (4A) evidenced by elemental analysis, thermogravimetric analysis (TGA) and powder X-ray diffraction (PXRD). Remarkably, in situ rapid and reversible dehydration-rehydration in static air occurs in 1-3, indicating their potential applications as water absorbent and sensing materials. Dehydrated 1 and 3 show selective gas adsorption of CO 2 over N2 and dehydrated 3 can adsorb methanol and ethanol vapors strongly. These compounds exhibit blue fluorescence in the solid state

Table_1_Sepsis as an independent risk factor in atrial fibrillation and cardioembolic stroke.docx

BackgroundElectrolyte balance is an important factor to sustain the homeostasis of human body environment and in sepsis pathogenesis. Many current cohort-based studies have already revealed that electrolyte disorder may intensify sepsis and induce stroke. However, the corresponding randomized controlled trials did not show that electrolyte disorder in sepsis has a harmful effect on stroke.ObjectivesThe aim of this study was to examine the association of genetically sepsis-derived electrolyte disorder with stroke risk using meta-analysis and Mendelian randomization.ResultsIn four studies (182,980 patients), electrolyte disorders were compared with stroke incidence in patients with sepsis. The pooled odds ratio (OR) of stroke is 1.79 [95% confidence interval (CI): 1.23–3.06; p ConclusionOur study revealed the association between electrolyte disorder and stroke in sepsis patients, and the correlation between genetic susceptibility to sepsis and increased risk of cardioembolic stroke, hinting that cardiogenic diseases and accompanying electrolyte disorder interference in due course could help sepsis patients get more benefits in stroke prevention.</p