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Aims The plasticity of vascular smooth muscle cells (VSMCs) enables them to alter phenotypes under various physiological and pathological stimuli. The alteration of VSMC phenotype is a key step in vascular diseases, including atherosclerosis. Although the transcriptome shift during VSMC phenotype alteration has been intensively investigated, uncovering multiple key regulatory signalling pathways, the translatome dynamics in this cellular process, remain largely unknown. Here, we explored the genome-wide regulation at the translational level of human VSMCs during phenotype alteration. Methods and results We generated nucleotide-resolution translatome and transcriptome data from human VSMCs undergoing phenotype alteration. Deep sequencing of ribosome-protected fragments (Ribo-seq) revealed alterations in protein synthesis independent of changes in messenger ribonucleicacid levels. Increased translational efficiency of many translational machinery components, including ribosomal proteins, eukaryotic translation elongation factors and initiation factors were observed during the phenotype alteration of VSMCs. In addition, hundreds of candidates for short open reading frame-encoded polypeptides (SEPs), a class of peptides containing 200 amino acids or less, were identified in a combined analysis of translatome and transcriptome data with a high positive rate in validating their coding capability. Three evolutionarily conserved SEPs were further detected endogenously by customized antibodies and suggested to participate in the pathogenesis of atherosclerosis by analysing the transcriptome and single cell RNA-seq data from patient atherosclerotic artery samples. Gain- and loss-of-function studies in human VSMCs and genetically engineered mice showed that these SEPs modulate the alteration of VSMC phenotype through different signalling pathways, including the mitogen-activated protein kinase pathway and p53 pathway. Conclusion Our study indicates that an increase in the capacity of translation, which is attributable to an increased quantity of translational machinery components, mainly controls alterations of VSMC phenotype at the level of translational regulation. In addition, SEPs could function as important regulators in the phenotype alteration of human VSMCs.

Escherichia coli ( E. coli) is the main cause of Gram-negative bacterial peritonitis among peritoneal dialysis patients. According to the 2016 update of the International Society for Peritoneal Dialysis Peritonitis Recommendations, drug susceptibilities of specific organisms should be regularly monitored. The aim of this study was to examine the evolution of antimicrobial resistance of E. coli peritonitis from 2006 to 2018. Two hundred and fifty-three episodes of E. coli peritonitis were enrolled in our study, corresponding to a rate of 0.024 episodes per patient-year. According to drug sensitivity test results, isolates were most sensitive to carbapenems, followed by cefmetazole, piperacillin/tazobactam, cefotetan and amikacin, with an overall rate of more than 90% in both cohorts. Cefazolin and ciprofloxacin resistance increased significantly from 2006–2011 to 2012–2018. Conversely, cefepime and ceftazidime resistance decreased significantly. The extended-spectrum β-lactamase (ESBL) rate fluctuated from 34.7% in 2006–2011 to 46.8% in 2012–2018. Compared with the ESBL-negative strains, ESBL-producing E. coli were more likely be resistant to ampicillin, ampicillin/sulbactam, cephalosporins, quinolones, aminoglycosides, furadantin and sulfamethoxazole and accounted for over 50% of the drug resistance. In the correlation analysis, E. coli displayed significantly increased resistance to cefazolin and ciprofloxacin, a finding correlated with ESBL production ( r = 0.883 and 0.276 respectively, p < 0.001 and p = 0.003). In conclusion, the rate of E. coli peritonitis declined stably in recent years, but the resistance to antimicrobial was high.

Enhancement of protein synthesis from mRNA translation is one of the key steps supporting cardiomyocyte hypertrophy during cardiac remodeling. The methyltransferase-like5 (METTL5), which catalyzes m

Nowadays, the development of electronic technology is changing every day. Computer technology has been widely used in various fields; therefore piano tuning teaching needs to keep pace with the social pace, and the tuning industry needs to be updated and explored to make it step on a new stage. In this study, the Fast Fourier Transform, Auto-correlation and Cepstrum feature extraction algorithms for audio visualization software were used to extract and visualize the audio features of seven piano tones from G4 to A4, and according to the characteristics the frequency was calculated and contrasted with the standard audio. Through the sound visualization analysis, it was found that the Auto-correlation algorithm was more consistent with the standard frequency. The use of sound visual tuning detection can plays an auxiliary role in piano tuning teaching.

The Hedgehog (Hh) signaling pathway plays a critical role in controlling patterning, growth and cell migration during embryonic development. Aberrant activation of Hh signaling has been linked to tumorigenesis in various cancers, such as basal cell carcinoma (BCC) and medulloblastoma. As a key member of the Hh pathway, the Smoothened (Smo) receptor, a member of the G protein-coupled receptor (GPCR) family, has emerged as an attractive therapeutic target for the treatment and prevention of human cancers. The recent determination of several crystal structures of Smo in complex with different antagonists offers the possibility to perform structure-based virtual screening for discovering potent Smo antagonists with distinct chemical scaffolds. In this study, based on the two Smo crystal complexes with the best capacity to distinguish the known Smo antagonists from decoys, the molecular docking-based virtual screening was conducted to identify promising Smo antagonists from ChemDiv library. A total of 21 structurally novel and diverse compounds were selected for experimental testing, and six of them exhibited significant inhibitory activity against the Hh pathway activation (IC50

Noncoding RNAs (ncRNAs) regulate gene expression in essential cellular processes and play key roles in many human diseases. Small nucleolar RNAs (snoRNAs) are a relatively large group of ncRNAs. Many studies have identified significant alterations of different snoRNAs in prostate, breast, and lung malignancies and that many of these snoRNAs have been shown to be processed into microRNA-like molecules known as snoRNA-derived RNAs (sdRNAs). Similarly, several small RNAs have also recently been found to be excised from well characterized tRNAs to function in both normal cellular metabolism and disease. In this paper, we present a new computational methodology for the identification, analysis, and visualization of ncRNA-derived RNAs (ndRNAs) with linear time and space complexity (named SURFr for Short Uncharacterized R NA Finder). We provide the results of our algorithm's running time by analyzing several publicly available datasets and finally discuss future research directions to our work.

Background Urgent-start peritoneal dialysis (PD) can help patients with end-stage renal diseases (ESRD) that are referred late to dialysis. However, catheter patency and related complications of urgent-start PD have not been thoroughly clarified. We investigated the clinical outcomes of urgent-start PD in a Chinese cohort. Methods We enrolled ESRD patients who received urgent-start PD (starting PD within 14 days after catheter insertion) in our center from January 1, 2006 to December 31, 2014, and followed them up for 10 years. The primary outcome was catheter failure. Secondary outcomes included short-term and long-term complications related to urgent-start PD. Results Totally 2059 patients (58.9% male, mean age 47.6 ± 15.9 years) were enrolled. Few perioperative complications were observed, including significant hemorrhage (n = 3, 0.1%) and bowel perforation (n = 0). Early peritonitis occurred in 24 (1.2%) patients (0.28 episodes per patient-year). Within the first month after catheter insertion, functional catheter malfunction occurred in 85 (4.1%) patients, and abdominal wall complications (including hernia, hydrothorax, hydrocele, and leakage) in 36 (1.7%) patients. During a median 36.5 (17.7–61.4) months of follow-up, 75 (3.6%) patients experienced catheter failure, and 291 (14.1%) had death-censoring technique failure. At the end of 1-month, 1 -year, 3-year, and 5-year, catheter patency rate was 97.6, 96.4, 96.2, 96.2%; and technique survival rate was 99.5, 97.0, 90.3, 82.7%, respectively. After adjusting for confounders, every 5-year increase in age was associated with 19% decrease of risk for catheter failure (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.73–0.89). Male sex (HR: 1.43, 95% CI: 1.00–2.04), diabetic nephropathy (HR: 1.56, 95% CI: 1.08–2.25) and low hemoglobin levels (HR: 0.89, 95% CI: 0.81–0.98) were independent risk factors for abdominal wall complications. Conclusions Urgent-start PD is a safe and efficacious option for unplanned ESRD patients. A well-trained PD team, a standardized catheter insertion procedure by experienced nephrologists, and a carefully designed initial PD prescription as well as comprehensive follow-up care, might be essential for the successful urgent-start PD program.

Table S1. Details of the organisms and the outcomes of the eraly peritonitis. Table S2. Details of the organisms and the outcomes of the early exit-site infections. (DOCX 13 kb)

Background Acute lymphoblastic leukemia is the most prevalent neoplasia among children. Despite the tremendous achievements of state-of-the-art treatment strategies, drug resistance is still a major cause of chemotherapy failure leading to relapse in pediatric acute lymphoblastic leukemia. The underlying mechanisms of such phenomenon are not yet clear and subject to further exploration. Prior research has shown that microRNAs can act as post-transcriptional regulators of many genes related to drug resistance. However, details of microRNA regulation mechanisms in pediatric acute lymphoblastic leukemia are far from completely understood. Methods We utilized a computational approach based upon emerging biomedical and biological ontologies and semantic technologies to investigate the important roles of microRNA: mRNA regulation on glucocorticoid resistance in pediatric acute lymphoblastic leukemia. In particular, various filtering mechanisms were designed based on the user-provided MeSH term to narrow down the most promising microRNAs in an effective manner. Results During our manual search on background literature, we found a total of 18 candidate microRNAs that possibly regulate glucocorticoid resistance in pediatric acute lymphoblastic leukemia. After the first-round filtering using the Broader-Match option where both the user-provided MeSH term and its direct parent term were utilized, the number of targets for 18 microRNAs was reduced from 232 to 74. During the second-round filtering with the Exact-Match option where only the MeSH term itself was utilized, the number of targets was further reduced to 19. Finally, we conducted semantic searches in the OmniSearch software tool on the five likely regulating microRNAs and identified two most likely microRNAs. Conclusions We successfully identified two microRNAs, hsa-miR-142-3p and hsa-miR-17-5p, which are computationally predicted to closely relate to glucocorticoid resistance, thus potentially serving as novel biomarkers and therapeutic targets in pediatric acute lymphoblastic leukemia.

Higher serum uric acid concentrations have been associated with higher bone mineral density in observational studies of older men and peri- or postmenopausal women, prompting speculation of a potential protective effect of uric acid on bone. Whether this relationship is present in the general population has not been examined and there is no data to support causality. We conducted a cross-sectional analysis of a probability sample of the US population. Demographic data, dietary intake, lifestyle risk factors and physical activity assessment data, serum biochemistry including serum uric acid, and bone mineral density were obtained from 6,759 National Health and Nutrition Examination Survey (NHANES; 2005-2010) participants over 30 years of age. In unadjusted analyses, higher serum uric acid levels were associated with higher bone mineral density at the femoral neck, total hip and lumbar spine in men, pre-menopausal women, and post-menopausal women not treated with estrogen. However, these associations were no longer statistically significant after adjustment for potential confounders, including age, body mass index, black race, alcohol consumption, estimated glomerular filtration rate (eGFR), serum alkaline phosphatase, and C-reactive protein (CRP). This is in contradistinction to some prevailing conclusions in the literature. To further examine the causal effect of higher serum uric acid on skeletal health, including biomechanical properties that are not measurable in humans, we used an established rat model of inducible mild hyperuricemia. There were no differences in bone mineral density, volume density, and biomechanical properties between hyperuricemic rats and normouricemic control animals. Taken together, our data do not support the hypothesis that higher serum uric acid has protective effects on bone health. This article is protected by copyright. All rights reserved

Acute lymphoblastic leukemia (ALL) is the most prevalent neoplasia among children, and drug resistance is still a major cause of chemotherapy failure in pediatric ALL. Prior research has shown that microRNAs (miRNAs) can play roles in such phenomenon, but detailed regulation mechanisms are far from completely understood. We utilized a semantic analysis approach and its MeSH term filtering mechanisms to explore the important roles of miRNA::mRNA regulation on glucocorticoid (GC) resistance in pediatric ALL. Hsa-miR-142-3p and hsa-miR-17-5p were predicted in this study to closely relate to GC resistance, thus potentially serving as novel biomarkers in pediatric ALL.

Elevation of serum phosphorus concentrations has been associated with cardiovascular events in older women and men. Whether age, sex, or estrogen therapy is associated with different phosphorus levels is unknown.Cross-sectional study.7,005 participants in the National Health and Nutrition Examination Survey (NHANES) 2003-2006.Demographic data; body measurement indexes; dietary intake by 24-hour dietary recall and food-frequency questionnaire; data for reproductive health, prescription medication, cardiovascular disease, osteoporosis, and diabetes mellitus obtained by questionnaire; and blood chemistry indexes.Serum phosphorus concentrations.In both males and premenopausal females, serum phosphorus levels decline progressively with age. In males, the decline continues over the entire age range of 21-85 years. In contrast, in females, serum phosphorus levels increase between ages 46-60 years (sex×age interaction; P0.001). The increase in serum phosphorus levels in older women is independent of changes in serum parathyroid hormone levels, daily dietary phosphorus intake, and estimated glomerular filtration rate. In analysis of covariance, we show that postmenopausal women receiving estrogen therapy have significantly lower serum phosphorus levels than non-estrogen users after adjusting for age, race, body mass index, daily dietary phosphorus intake, and serum albumin, serum parathyroid hormone, and 25-hydroxyvitamin D levels (3.83 vs 3.98mg/dL; P0.001).The study was cross-sectional in design and estrogen therapy was not randomly assigned or concealed. Important phosphorus regulatory factors such as serum fibroblast growth factor 23 and klotho were not available in the study.Estrogen status may account for the difference in serum phosphorus levels in postmenopausal women.

Low levels of the adipocyte-secreted protein adiponectin correlate with albuminuria in both mice and humans, but whether adiponectin has a causative role in modulating renal disease is unknown. Here, we first generated a mouse model that allows induction of caspase-8-mediated apoptosis specifically in podocytes upon injection of a construct-specific agent. These POD-ATTAC mice exhibited significant kidney damage, mimicking aspects of human renal disease, such as foot process effacement, mesangial expansion, and glomerulosclerosis. After the initial induction, both podocytes and filtration function recovered. Next, we crossed POD-ATTAC mice with mice lacking or overexpressing adiponectin. POD-ATTAC mice lacking adiponectin developed irreversible albuminuria and renal failure; conversely, POD-ATTAC mice overexpressing adiponectin recovered more rapidly and exhibited less interstitial fibrosis. In conclusion, these results suggest that adiponectin is a renoprotective protein after podocyte injury. Furthermore, the POD-ATTAC mouse provides a platform for further studies, allowing precise timing of podocyte injury and regeneration.

We immobilized carbonic anhydrase (CA) onto the surface of membrane oxygenator of polymethyl pentene (PMP) to enhance the removal of carbon dioxide in blood by two steps. We first introduced hydroxyl groups onto PMP surface by water plasma treatment, and then coupled CA onto PMP surface by using cyanate bromide (CNBr) as a crosslinker. After plasma treatment, the contact angle with water and chemical composition of PMP surface were characterized by analysis system of surface contact angle and XPS. Using p-nitrophenyl acetate (p-NPA) as a substrate, the activity, concentration, storage stability and re-usability of immobilized CA on PMP hollow fibers were studied by ultraviolet spectrophotometer. The preliminary data showed that hydroxyl groups could be introduced on the surface of PMP by water plasma treatment, and CA with catalysis activity could be successfully introduced onto PMP surface in high immobilization efficiency. The activity of covalently immobilized CA increased with the increase of concentration of CNBr, and the maximum was 73% of the theoretical activity of CA spread on PMP surface in monolayer in studied range. Covalently immobilized CA showed higher reusability compared to physically adsorbed CA, and higher storage stability compared to free CA in solution at 37 degrees C. The method would be used potentially in the membrane oxygenator to improve the capacity of removal of carbon dioxide in blood in the future.