Serum uromodulin and progression of kidney disease in patients with chronic kidney disease

Abstract Background Uromodulin is specifically synthesized and secreted by kidney tubular epithelial cells. Studies on the association of serum uromodulin and outcomes of chronic kidney disease (CKD) are lacking. This study aimed to evaluate whether serum uromodulin was associated with outcomes of patients with CKD. Methods We measured serum uromodulin concentrations by ELISA in 2652 CKD patients from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) and investigated the association of serum uromodulin with outcomes of CKD patients, including end-stage kidney disease (ESKD) receiving kidney replacement therapy, cardiovascular events and mortality by Cox proportional hazards regression model. Results A total of 2652 CKD patients were enrolled in this study, with an age of 48.7 ± 13.8 years and the baseline eGFR of 49.6 ± 29.4 mL/min/1.73 m2, of whom 58.4% were male. The median level of urinary albumin/creatinine ratio and serum uromodulin was 473.7 mg/g (IQR 134.1–1046.6 mg/g) and 77.2 ng/mL (IQR 48.3–125.9 ng/mL), respectively. Altogether, 404 ESKD, 189 cardiovascular events, and 69 deaths occurred during the median follow-up of 53.6 (IQR 44.0–64.0) months. Lower levels of serum uromodulin were independently associated with higher risk of incident ESKD after adjusting for traditional cardiovascular risk factors, with the hazard ratios (HRs) of 3.23 (95% confidence intervals [CIs] 2.15–4.85) for the middle tertile and 7.47 (95% CI 5.06–11.03) for the bottom tertile, compared with top tertile and 0.31 (95% CI 0.25–0.38) per every standard deviation increase. After further adjustment for the baseline eGFR, the association was greatly attenuated, but still significant, with HRs of 1.92 (95% CI 1.26–2.90) for the bottom tertile compared with top tertile and 0.69 (95% CI 0.55–0.86) per every standard deviation increase. Conclusions Serum uromodulin is independently associated with an increased risk of incident ESKD in CKD patients.https://deepblue.lib.umich.edu/bitstream/2027.42/146520/1/12967_2018_Article_1693.pd

Electrotunable liquid sulfur microdroplets.

Manipulating liquids with tunable shape and optical functionalities in real time is important for electroactive flow devices and optoelectronic devices, but remains a great challenge. Here, we demonstrate electrotunable liquid sulfur microdroplets in an electrochemical cell. We observe electrowetting and merging of sulfur droplets under different potentiostatic conditions, and successfully control these processes via selective design of sulfiphilic/sulfiphobic substrates. Moreover, we employ the electrowetting phenomena to create a microlens based on the liquid sulfur microdroplets and tune its characteristics in real time through changing the shape of the liquid microdroplets in a fast, repeatable, and controlled manner. These studies demonstrate a powerful in situ optical battery platform for unraveling the complex reaction mechanism of sulfur chemistries and for exploring the rich material properties of the liquid sulfur, which shed light on the applications of liquid sulfur droplets in devices such as microlenses, and potentially other electrotunable and optoelectronic devices

Mapping forests in monsoon Asia with ALOS PALSAR 50-m mosaic images and MODIS imagery in 2010.

Extensive forest changes have occurred in monsoon Asia, substantially affecting climate, carbon cycle and biodiversity. Accurate forest cover maps at fine spatial resolutions are required to qualify and quantify these effects. In this study, an algorithm was developed to map forests in 2010, with the use of structure and biomass information from the Advanced Land Observation System (ALOS) Phased Array L-band Synthetic Aperture Radar (PALSAR) mosaic dataset and the phenological information from MODerate Resolution Imaging Spectroradiometer (MOD13Q1 and MOD09A1) products. Our forest map (PALSARMOD50 m F/NF) was assessed through randomly selected ground truth samples from high spatial resolution images and had an overall accuracy of 95%. Total area of forests in monsoon Asia in 2010 was estimated to be ~6.3 × 10(6 )km(2). The distribution of evergreen and deciduous forests agreed reasonably well with the median Normalized Difference Vegetation Index (NDVI) in winter. PALSARMOD50 m F/NF map showed good spatial and areal agreements with selected forest maps generated by the Japan Aerospace Exploration Agency (JAXA F/NF), European Space Agency (ESA F/NF), Boston University (MCD12Q1 F/NF), Food and Agricultural Organization (FAO FRA), and University of Maryland (Landsat forests), but relatively large differences and uncertainties in tropical forests and evergreen and deciduous forests

Genome-wide CRISPR/Cas9 screening for drug resistance in tumors

Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated nuclease 9 (Cas9) screening is a simple screening method for locating loci under specific conditions, and it has been utilized in tumor drug resistance research for finding potential drug resistance-associated genes. This screening strategy has significant implications for further treatment of malignancies with acquired drug resistance. In recent years, studies involving genome-wide CRISPR/Cas9 screening have gradually increased. Here we review the recent application of genome-wide CRISPR/Cas9 screening for drug resistance, involving mitogen-activated protein kinase (MAPK) pathway inhibitors, poly (ADP-ribose) polymerase inhibitors (PARPi), alkylating agents, mitotic inhibitors, antimetabolites, immune checkpoint inhibitors (ICIs), and cyclin-dependent kinase inhibitors (CDKI). We summarize drug resistance pathways such as the KEAP1/Nrf2 pathway MAPK pathway, and NF-κB pathway. Also, we analyze the limitations and conditions for the application of genome-wide CRISPR/Cas9 screening techniques

Fast Green FCF Attenuates Lipopolysaccharide-Induced Depressive-Like Behavior and Downregulates TLR4/Myd88/NF-κB Signal Pathway in the Mouse Hippocampus

Depression is a common neuropsychiatric disorder and new anti-depressive treatments are still in urgent demand. Fast Green FCF, a safe biocompatible color additive, has been suggested to mitigate chronic pain. However, Fast green FCF’s effect on depression is unknown. We aimed to investigate Fast green FCF’s effect on lipopolysaccharide (LPS)-induced depressive-like behavior and the underlying mechanisms. Pretreatment of Fast green FCF (100 mg/kg, i.p. daily for 7 days) alleviated depressive-like behavior in LPS-treated mice. Fast green FCF suppressed the LPS-induced microglial and astrocyte activation in the hippocampus. Fast green FCF decreased the mRNA and protein levels of Toll-like receptor 4 (TLR4) and Myeloid differentiation primary response 88 (Myd88) and suppressed the phosphorylation of nuclear factor-κB (NF-κB) in the hippocampus of LPS-treated mice. Fast green FCF also downregulated hippocampal tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, but did not alter the level of the brain-derived neurotrophic factor (BDNF) in the hippocampus of LPS-treated mice. The molecular docking simulation predicts that Fast green FCF may interact with TLR4 and interrupt the formation of the TLR4-MD2 complex. In conclusion, the anti-depressive action of Fast green FCF in LPS-treated mice may involve the suppression of neuroinflammation and the downregulation of TLR4/Myd88/NF-κB signal pathway in mouse hippocampus. Our findings indicate the potential of Fast green FCF for controlling depressive symptoms

Protocol for a Single-Center Randomized Controlled Trial of Percutaneous Coronary Intervention Via Distal Transradial Access Versus Transradial Access

Background: Although transradial access (TRA) has become the main vascular access for coronary intervention, its high radial artery occlusion rate limits its application in some patients. Studies have shown that compared with TRA, distal transradial access (dTRA) with the snuffbox area or the Hegu acupoint area as the puncture point significantly decreases the incidence of radial artery occlusion. However, no randomized controlled study has confirmed the safety and efficacy of coronary artery intervention via dTRA in China. Methods and analyses: This single-center, prospective, randomized controlled, superiority open-label study will enroll 428 consecutive patients with coronary heart disease undergoing percutaneous coronary intervention as the study population. After preoperative evaluation, the participants will be randomly divided into a study group (dTRA) and control group (TRA) in a 1:1 ratio. The primary endpoint (radial artery occlusion at 24 hours after operation) and secondary endpoint events will be evaluated and recorded. Study registration: This study has been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2300073902)

High Prevalence of Extended-Spectrum Beta Lactamases among Salmonella enterica Typhimurium Isolates from Pediatric Patients with Diarrhea in China

We investigated the extended-spectrum beta lactamases among 62 Salmonella enterica Typhimurium isolates recovered from children with diarrhea in a Chinese pediatric hospital. A large proportion of S. enterica Typhimurium isolates were resistant to multiple antimicrobial agents, including ampicillin (90.3%), tetracycline (80.6%), trimethoprim/sulfamethoxazole (74.2%), chloramphenicol (66.1%), cefotaxime (27.4%). Forty-nine (79.0%) of S. enterica Typhimurium isolates were positive for blaTEM-1b and resistant to ampicillin. Thirteen S. enterica Typhimurium isolates (21.0%) were positive for blaCTX-M-1-group and blaCTX-M-9-group, and all isolates harboring blaCTX-M genes were positive for ISEcp1. Two main clones (PFGE type A and D) accounted for nearly 70% of S. enterica Typhimurium isolates, and 7 CTX-M-producing isolates belonged to PFGE type D. Collectively, our data reveal multi-drug resistance and a high prevalence of extended spectrum beta lactamases among S. enterica Typhimurium isolates from children in China. In addition, we report the first identification of blaCTX-M-55 within Salmonella spp. Our data also suggest that clonal spread is responsible for the dissemination of S. enterica Typhimurium isolates

Infertile human endometrial organoid apical protein secretions are dysregulated and impair trophoblast progenitor cell adhesion

IntroductionEmbryo implantation failure leads to infertility. As an important approach to regulate implantation, endometrial epithelial cells produce and secrete factors apically into the uterine cavity in the receptive phase to prepare the initial blastocyst adhesion and implantation. Organoids were recently developed from human endometrial epithelium with similar apical-basal polarity compared to endometrial gland making it an ideal model to study endometrial epithelial secretions.MethodsEndometrial organoids were established using endometrial biopsies from women with primary infertility and normal fertility. Fertile and infertile organoids were treated with hormones to model receptive phase of the endometrial epithelium and intra-organoid fluid (IOF) was collected to compare the apical protein secretion profile and function on trophoblast cell adhesion.ResultsOur data show that infertile organoids were dysregulated in their response to estrogen and progesterone treatment. Proteomic analysis of organoid apical secretions identified 150 dysregulated proteins between fertile and infertile groups (>1.5-fold change). Trophoblast progenitor spheroids (blastocyst surrogates) treated with infertile organoid apical secretions significantly compromised their adhesion to organoid epithelial cell monolayers compared to fertile group (P < 0.0001).DiscussionThis study revealed that endometrial organoid apical secretions alter trophoblast cell adhesiveness relative to fertility status of women. It paves the way to determine the molecular mechanisms by which endometrial epithelial apical released factors regulate blastocyst initial attachment and implantation

Basic Mechanical Properties of Duplex Stainless Steel Bars and Experimental Study of Bonding between Duplex Stainless Steel Bars and Concrete

In recent years, as a result of the large-scale use of stainless steel bars in production and life, people’s demand for stainless steel bars has increased. However, existing research information on stainless steel bars is scant, especially the lack of research on the mechanical properties of duplex stainless steel bars and the bonding properties of duplex stainless steel bars to concrete. Therefore, this paper selects 177 duplex stainless steel bars with different diameters for room temperature tensile test, and then uses mathematical methods to provide suggestions for the values of their mechanical properties. The test results show that the duplex stainless steel bar has a relatively high tensile strength of 739 MPa, no significant yield phase, and a relatively low modulus of elasticity of 1.43 × 105 MPa. In addition, 33 specimens were designed to study the bonding properties of duplex stainless steel bars to concrete. In this paper, the effects of concrete strength, duplex stainless steel reinforcement diameter, the ratio of concrete cover to reinforcing steel diameter, and relative anchorage length on the bond stress were investigated, and a regression model was established based on the experimental results. The results show that, with the concrete strength concrete strength from C25 to C40, the compressive strength of concrete increased by 56.1%, the bond stress increased by 27%; the relative anchorage length has been increased from 3 to 6, the relative anchorage length has doubled, and the bond stress has increased by 13%; and, the ratio of concrete cover to reinforcing steel diameter increased to a certain range on the bond stress has no significant effect and duplex stainless steel reinforcement diameter has little effect on the bond stress. The ratio of concrete cover to reinforcing steel diameter from 3.3 to 4.5 and the bond stress increased by 24.7%. A ratio of concrete cover to reinforcing steel diameter greater than 4.5 has no significant effect on the bond stress, with the average bond stress value of 20.1 MPa. The duplex stainless steel bar diameter has little effect on the bond stress for the diameters of 12 mm, 16 mm, 25 mm duplex stainless steel bar, and their average bond stress is 19.9 MPa

Comparing Different Spatial Resolutions and Indices for Retrieving Land Surface Phenology for Deciduous Broadleaf Forests

Deciduous broadleaf forests (DBF) are an extremely widespread vegetation type in the global ecosystem and an indicator of global environmental change; thus, they require accurate phenological monitoring. However, there is still a lack of systematic understanding of the sensitivity of phenological retrievals for DBF in terms of different spatial resolution data and proxy indices. In this study, 79 globally distributed DBF PhenoCam Network sites (total 314 site-years, 2013–2018) were used as the reference data (based on green chromaticity coordinates, GCC). Different spatial resolutions (30 m Landsat and Sentinel-2 data, and 500 m MCD43A4 data) and satellite remote sensing vegetation indices (normalized difference vegetation index, NDVI; enhanced vegetation index, EVI; and near-infrared reflectance of vegetation, NIRV) were compared to find the most suitable data and indices for DBF phenological retrievals. The results showed that: (1) for different spatial resolutions, both 30 m Landsat–Sentinel-2 data and 500 m MODIS data accurately captured (R2 > 0.8) DBF phenological metrics (i.e., the start of the growing season, SOS, and the end of the growing season, EOS), which are associated with the comparatively homogeneous landscape pattern of DBF; (2) for SOS, the NIRv index was closer to GCC than EVI and NDVI, and it showed a slight advantage over EVI and a significant advantage over NDVI. However, for EOS, NDVI performed best, outperforming EVI and NIRv; and (3) for different phenological metrics, the 30 m data showed a significant advantage for detecting SOS relative to the 500 m data, while the 500 m MCD43A4 outperformed the 30 m data for EOS. This was because of the differences between the wavebands used for GCC and for the satellite remote sensing vegetation indices calculations, as well as the different sensitivity of spatial resolution data to bare soil. This study provides a reference for preferred data and indices for broad scale accurate monitoring of DBF phenology