Polymorphisms of the bovine chemokine receptor-like 1 gene and their associations with meat quality traits in Qinchuan cattle ( Bos taurus )

Background: We investigated the polymorphisms of the bovine chemokine receptor-like 1(CMKLR1) gene. The coding region of CMKLR1 was screened in Qinchuan cattle by PCR-RFLP technology. Results: In this study, we discovered two single nucleotide polymorphisms (SNPs) (264G > C and 762C > T) in the coding region of the CMKLR1 gene. Hence, we described the BmgT120l and Pdm1 PCR-RFLP methods for detecting the 64G > C and 762C > T mutations, respectively. PCR-RFLP and sequencing were used to analyze the two loci of CMKLR1 gene in 324 individuals, which were randomly selected from breeding populations. Furthermore, meat quality traits in another 80 Qinchuan individuals were analyzed by the comparison between the genotypes and their phenotypic data. Conclusions: The results showed that the G264C SNP and C762T SNP of bovine CMKLR1 were significantly associated with backfat thickness (BFT) and water holding capacity (WHC), respectively

EZH2 Regulates Protein Stability via Recruiting USP7 to Mediate Neuronal Gene Expression in Cancer Cells

Misexpression of chromatin modification factors and changed epigenetic modifications play crucial roles for tumorigenesis. Our previous studies demonstrated that inhibition of epigenetic modification enzymes EZH2, LSD1, DNMTs, and HDACs caused post-mitotic neuron-like differentiation in different cancer cells. However, how they regulate neuronal differentiation in cancer cells was unknown. Here, we show that EZH2, LSD1, DNMT1, and HDAC1 form interactions themselves, meanwhile, they also interact with SMAD proteins and β-CATENIN in cancer cells. Chemical inhibition of these enzymes leads to reduced level of proteins except HDAC1. The change in protein level and/or enzymatic activities further result in changed chromatin modifications on neuronal gene promoters, and activation of neuronal genes. Inhibition of these enzymes in neural progenitor cells (NPCs) also caused neuronal differentiation, similar to cancer cells. Particularly, EZH2 interacts with and required for the stability of LSD1, HDAC1, DNMT1, β-CATENIN, or SMAD2/4, via recruitment of deubiquitinase USP7. Reduced EZH2 leads to enhanced ubiquitination and degradation of these proteins, and decreased binding of LSD1, HDAC1, and DNMT1 to neuronal gene promoters, and lessened Wnt and TGFβ target gene activation. Hence, EZH2 sustains a series of proteins that promote tumorigenesis, in addition to its original function of histone methylation. Considering together with other studies, we conclude that these chromatin modification factors function in the same way in cancer cells as in neural progenitor/stem cells. The similarity between cancer cells and neural progenitor/stem cells provides an insight into the essence and unified framework for cancer initiation and progression, and are suggestive for novel strategies of cancer therapy

Stachydrine Ameliorates Cardiac Fibrosis Through Inhibition of Angiotensin II/Transformation Growth Factor β1 Fibrogenic Axis

Cardiovascular diseases, the leading cause of death worldwide, are tightly associated with the pathological myocardial fibrosis. Stachydrine (Sta), a major active compound in Chinese motherwort Leonurus heterophyllus, was reported to effectively attenuate cardiac fibrosis, but the cellular and molecular mechanism remains unclear. In this study, the anti-fibrotic effect of Sta and mechanism underlying were explored in a mouse model of pressure overload and AngII stimulated cardiac fibroblasts (CFs). Mice were randomly divided into sham, transverse aorta constriction with saline (TAC+Sal), TAC with telmisartan (TAC+Tel), and TAC with Sta (TAC+Sta) groups. Cardiac morphological and functional changes were evaluated by echocardiography and histological methods, and the molecular alterations were detected by western blotting. Primary cultured neonatal mouse CFs were treated with or without angiotensin II (AngII, 10−7 M), transformation growth factor β1 (TGFβ1, 10 ng/mL), and different dosage of Sta (10−6–10−4 M) for up to 96 h, and cell proliferation, cytotoxicity, morphology and related signals were also detected. The in vivo results revealed that TAC prominently induced cardiac dysfunction, left ventricular dilation, myocardial hypertrophy, and elevated myocardial collagen deposition, accompanied with increased fibrotic markers including α-smooth muscle actin (α-SMA) and periostin. However, Sta treatment partially reversed cardiac morphological and functional deteriorations, and significantly blunted cardiac fibrosis as well as Tel. Increments of myocardial angiotensinogen (AGT), angiotensin converting enzyme (ACE), AngII type 1 receptor (AT1R), and TGFβ1 transcripts, together with increased protein levels of ACE and AngII, after TAC were dramatically down-regulated by Sta treatment. Coincidently, in vitro experiments demonstrated that AngII stimulation in CFs led to up-regulation of AT1R and TGFβ1, and therefore promoted CFs trans-differentiating into hyper-activated myocardial fibroblasts (MFs) as evidenced by increased cell proliferation, collagen and fibrotic makers. On the contrary, Sta potently down-regulated but not directly inhibited AT1R, suppressed TGFβ1 production, and the pro-fibrotic effect of AngII in CFs. Moreover, activation of TGFβ1/Smads signal in the fibrotic process were observed both TAC model and in AngII stimulated CFs, which were also notably blunted by Sta. However, Sta failed to abolish the activation of CFs triggered by TGFβ1. Taken together, it was demonstrated in this study that Sta suppressed ACE/AngII/AT1R-TGFβ1 profibrotic axis, especially on the de novo production of AngII via down-regulating AGT/ACE and AT1R, and therefore inactivated CFs and blunted MFs transition, which ultimately prevented cardiac fibrosis

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Flexible electrochemical biosensors based on interfacially assembled metal nanocrystals and graphene paper

This study focuses on the fabrication of hybrid flexible electrodes to detect molecules related to human health. The hybrid electrodes were built upon flexible graphene paper and novel noble metal nanostructures. The size, morphology and surface chemistry of noble metal nanoparticles were well tailored using wet chemical method. Moreover, functionalized noble nanostructures were assembled at the interface between water and organic solvents and transferred on the flexible graphene paper via dip-coating. The fabricated free-standing flexible hybrid electrodes were further applied to detect biomolecules (such as dopamine and nitric oxide) released from living cells under external stimuli and heavy metals released from degraded quantum dots uptake inside living cells. Owing to the high loading density of 2D-assembled nanocrystals, remarkable electrocatalytic activity of nanocrystals and good conductivity of flexible graphene paper, the constructed sensors exhibited excellent performances toward detection a range of targets. Thus, this work illustrated a simple and novel approach to the further development of point-of-care electrochemical devices.DOCTOR OF PHILOSOPHY (SCBE

Coating graphene paper with 2D-assembly of electrocatalytic nanoparticles : a modular approach toward high-performance flexible electrodes

The development of flexible electrodes is of considerable current interest because of the increasing demand for modern electronics, portable medical products, and compact energy devices. We report a modular approach to fabricating high-performance flexible electrodes by structurally integrating 2D-assemblies of nanoparticles with freestanding graphene paper. We have shown that the 2D array of gold nanoparticles at oil–water interfaces can be transferred on freestanding graphene oxide paper, leading to a monolayer of densely packed gold nanoparticles of uniform sizes loaded on graphene oxide paper. One major finding is that the postassembly electrochemical reduction of graphene oxide paper restores the ordered structure and electron-transport properties of graphene, and gives rise to robust and biocompatible freestanding electrodes with outstanding electrocatalytic activities, which have been manifested by the sensitive and selective detection of two model analytes: glucose and hydrogen peroxide (H2O2) secreted by live cells. The modular nature of this approach coupled with recent progress in nanocrystal synthesis and surface engineering opens new possibilities to systematically study the dependence of catalytic performance on the structural parameters and chemical compositions of the nanocrystals

N-(2-hydroxypropyl)-3-trimethylammonium chitosan-poly(epsilon-caprolactone) copolymers and their antibacterial activity

National Key Universities of China [M2009032]Chitosan-poly(epsilon-caprolactone) (CPC) copolymers were synthesized via an amino-group-protection method Selected CPCs with poly(epsilon-caprolactone) content less than 50 wt% were further modified by introducing quaternary ammonium groups It was found that the maximum degree of quaternization for some quaternized CPCs (q-CPCs) could reach around 38% under present synthesis conditions The optimized q-CPCs showed various antibacterial activities in vitro and they were able to completely prevent growth of Staphylococcus aureus and Escherichia coli at different concentrations of about 0 2% and 0 25% respectively At lower concentrations these optimal q-CPCs had higher antibacterial activities against both bacteria as compared to chitosan The optimized q-CPCs were also processed Into membranes for tensile mechanical investigations and the resulting membranes exhibited notably higher strength and modulus in wet state but much lower strength and modulus in dry state when they were compared with chitosan membranes Results suggested that the optimal q-CPCs with proper compositional proportions could have the potential for certain kinds of antibacterial applications where desirable tensile strength in wet state is required (C) 2010 Elsevier Ltd All rights reserve