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Chronic kidney disease (CKD) is a common condition in worldwide with underlying causes. The role of trace elements such as copper and zinc in CKD is uncertain. We aimed to examine the relationship of serum copper and zinc with kidney function status and explore its possible effect modifiers in the general population.Data from 5353 National Health and Nutrition Examination Survey (NHANES) participants from 2011 to 2016 were analyzed for the role of trace elements in the age range 18 to 80 years. The kidney outcomes were reduced estimated glomerular filtration rate (eGFR)60 mL/min/1.73 mFindings showed a significant positive association between serum copper and urinary ACR (OR = 1.04, 95% CI = 1.00-1.07). Serum copper levels of 18.0 μmol/L (median) or higher (reference level18.0 μmol/L) were significantly associated with increased urinary ACR (OR = 1.67, 95% CI = 1.21-2.31) after adjusting for confounding factors. In contrast, there was a significant inverse association between serum zinc and reduced eGFR (OR = 0.89,95% CI = 0.81-0.99). Where serum zinc level was greater than 12.3 μmol/L (median), the prevalence of reduced eGFR was lower (OR = 0.65, 95% CI = 0.16-0.60). In addition, a stratified analysis based on various risk factors found that in those individuals with serum albumin greater than 43 g/L or systolic blood pressure greater than 120 mmHg, positive correlations between serum copper and risk of increased urinary ACR was more significant.Our findings suggest that the reference levels of serum copper and zinc levels in healthy individuals may be different from current understanding. If further studies substantiate the same, the results will be a useful guide for designing future clinical trials and nutritional guidelines.

Chiral cyclic tetraphenylethylenes (TPEs) were synthesized by cyclization with chiral binaphthols. The helical conformation can be immobilized and multi-isomers can be separated resulting from (

The distal end of grape berries preferentially cracks during the soaking process in vitro, which may be related to preferential water uptake and cell anatomy. Thus, the relationship between water uptake and cell anatomical structure was assessed using 49 grape varieties. In vitro immersion experiments were performed on mature berries to measure the differences in berry-cracking properties. A whole-berry in vitro staining method was used to trace the water uptake of the vascular bundles, and paraffin sections were used to observe and analyze the structural parameters of the different tissues. The results showed that the berry-cracking rate and water uptake of the distal end of berries prone to cracking were significantly higher than that of the resistant berries. Compared with the berries that were resistant to cracking, the berries that were prone to cracking possessed a thin cuticle, epidermis and sub-epidermis. Dye accumulated in the distal end of the cracking-prone berries, which even exhibited cracking during the dyeing process. However, less dye accumulated on the surface of the cracking-resistant varieties and was only sporadically distributed on the surface. In addition, cracking of the distal end of the berry may also be related to other shape and size parameters of the cells in cell layer. Analysis of vascular bundle water transport and the differences in the cell structure characteristics of the different varieties, offered a preliminary explanation for why the distal end of the berry is prone to cracking, providing theoretical support for further research on the mechanisms of berry cracking.

Salinity and drought stress are major abiotic stresses negatively affecting the growth and productivity of alfalfa (Medicago sativa L.). Exploration of genes exhibiting superior tolerance to salinity and drought stress in alfalfa will help aid target molecular breeding and developing tolerant forages. In this study, we adopted a high-efficient yeast FOX hunting system for the identification of salinity and drought tolerant genes in alfalfa. Based on the Gateway-compatible vector system, a high-quality expression library was constructed, containing 1.3 × 107 clones with an average size of 1.44 kb. Through heterologous transformation of mixed library plasmid into salt or drought sensitive yeast mutants, monoclonal resistant strains were screened and tolerant genes were captured. Eighteen salinity-tolerance genes were obtained which were involved in several pathways, containing GRAS and zinc finger transcriptional factors, PP2A interaction module, ERVT vesicle transporter and LETM transmembrane protein. Twelve drought tolerance genes were separated, including ERF and SCL transcriptional factors, CIPK and BSK protein kinases, TGL-type ligase, cPGM and cPDL protease. The mRNA transcription levels of these tolerant genes were inducible or suppressible for response to salt or drought stress conditions following quantitative PCR detection, respectively. Furthermore, heterologous transformation of ERVT and CIPK11 can improve the salt and drought stress tolerance in Arabidopsis, which indicates the conservative function of the screening gene in yeast and Arabidopsis. Obtaining these candidate genes can provide new insights for future research with respect to plant salt and drought tolerance.

With the rapidly increasing healthcare cost and the scarcity of inpatient resources, it is of paramount importance to accurately predict the healthcare resource utilization. Previous research mainl...

There have been rapidly growing applications using machine learning models for predictive analytics in Electronic Health Records (EHR) to improve the quality of hospital services and the efficiency of healthcare resource utilization. A fundamental and crucial step in developing such models is to convert medical codes in EHR to feature vectors. These medical codes are used to represent diagnoses or procedures. Their vector representations have a tremendous impact on the performance of machine learning models. Recently, some researchers have utilized representation learning methods from Natural Language Processing (NLP) to learn vector representations of medical codes. However, most previous approaches are unsupervised, i.e. the generation of medical code vectors is independent from prediction tasks. Thus, the obtained feature vectors may be inappropriate for a specific prediction task. Moreover, unsupervised methods often require a lot of samples to obtain reliable results, but most practical problems have very limited patient samples. In this paper, we develop a new method called Prediction Task Guided Health Record Aggregation (PTGHRA), which aggregates health records guided by prediction tasks, to construct training corpus for various representation learning models. Compared with unsupervised approaches, representation learning models integrated with PTGHRA yield a significant improvement in predictive capability of generated medical code vectors, especially for limited training samples.

Vascular calcification such as arteriosclerosis, which is characterized by a calcification of the tunica media, is a severe complication of chronic kidney disease (CKD), contributing to the high prevalence of cardiovascular morbidity and mortality in patients with CKD. An essential step during the development of arteriosclerosis is the transdifferentiation/calcification of vascular smooth muscle cells (VSMCs), resembling osteogenesis. Metabolic acidosis, a common clinical manifestation in CKD, is known to decrease vascular calcification. To understand the underlying regulatory mechanisms of acidosis, we investigated whether the acidosis-decreased VSMC calcification involves altered signaling of the LTCC/Ca2+/Runx2 pathway. Vascular calcifications, calcium content, runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), L-type calcium channel (LTCC) β3 subunits, and calcium influx were measured in vivo or in vitro. Calcified nodules and calcium content increased either in aorta sections of vascular calcified rats or in VSMCs induced by β-GP. The expression of Runx2 and ALP activity markedly rose, accompanied by the increasing expression of LTCC β3 subunits and calcium influx. However, acidosis supplementation successfully attenuated VC and VSMC calcification and inhibited Runx2, ALP, LTCC β3 subunits, and calcium influx. In conclusion, acidosis significantly attenuated vascular calcification in association with downregulation of the LTCC/Ca2+/Runx2 pathway.

Genetic variants may affect the interactions between microRNAs (miRNAs/miRs) and their target genes by modulating their binding affinity or by creating, or destroying a miRNA-binding site. SET domain containing (lysine methyltransferase) 8 (SET8) is the sole lysine methyltransferase that catalyzes the monomethylation of histone H4 lysine 20, and is associated with tumor growth, invasion and metastasis. In the present study, the rs16917496 polymorphism within the miR-502 binding site of the SET8 mRNA 3' untranslated region (3'UTR) in patients with clear cell renal cell carcinoma (ccRCC) and healthy controls was genotyped. The SET8 CC genotype was associated with a decreased ccRCC risk compared with the CT [P=0.003; odds ratio (OR)=0.318; 95% confidence interval (CI), 0.146-0.691], TT (P=0.011; OR=0.402; 95% CI, 0.197-0.819) and CT+TT (P=0.004; OR=0.370; 95% CI, 0.186-0.736) genotypes. The SET8 CC genotype was associated with reduced SET8 expression based on immunostaining of ccRCC tissue. Low SET8 protein levels were negatively associated with tumor-node-metastasis staging in patients with ccRCC according to the size of tumor and lymph node metastases. SET8-knockdown inhibited renal carcinoma 786-O cell proliferation, migration and invasion. c-Myc and matrix metalloproteinase-7 mRNA expression were downregulated upon SET8-knockdown in renal carcinoma 786-O cells. These data indicated that SET8 may be a functional tumor promoter and that its activation, which is partially regulated by changing the miR-502 and SET8 3'UTR binding affinity, may serve an important role in ccRCC development.

Plants have developed a complex regulatory networks to appropriately regulate copper homeostasis in response to the frequently-changing availability of copper (Cu). However, little is known about miRNA-mediated Cu-regulatory networks in grapevine. To depict the regulatory mechanism of Cu-responsive microRNAs (miRNAs) in grapevine, three conserved Cu-responsive miRNAs (miR397, miR398 and miR408) that had the most copies of the Cu-response element (CuRE) were investigated in response to copper availability. It was found that the suppression of Cu-associated miRNAs followed by the up-regulation of their target genes encoding Cu-containing proteins. Four target genes such as vvi-LAC4 and vvi-LAC17 for miR397, vvi-PC and vvi-LAC12 for miR408 were experimentally verified by RLM-RACE. The results showed that these vvi-miRNAs negatively regulated expression of their target mRNAs through guiding corresponding target mRNA cleavage. Analysis of cis-elements showed that three miRNAs were not only in response to Cu stress but also involved in a complicated regulation network to respond to environmental stress. Our results are of good help for better understanding miRNA-guided Cu stress regulatory networks in grapevine.

Grape (Vitis vinifera L.) is one of the most widely cultivated fruit crops globally. Fruit cracking during fruit growth and development severely affects yield and quality, resulting in significant economic losses. Currently, calcium fertilizer application is used to prevent berry cracking. However, the mechanisms by which calcium fertilizer treatment reduces berry cracking are poorly understood. To explore this, transcriptomics and metabolomics were used to identify the differentially expressed genes (DEGs) and differentially abundant metabolites in V. vinifera ‘90-1’. We found that secondary metabolic pathways were enriched during the veraison and maturity stages, including the flavonoid biosynthesis pathway. Enrichment analysis indicated that most of the DEGs were enriched in the functional category of flavonoid biosynthesis. As secondary metabolites are largely antioxidants, the spraying of calcium fertilizers may improve the antioxidant capacity of the berries by regulating genes related to the flavonoid metabolism pathway, thus reducing the occurrence of berry cracking.

Although great progress has been made towards understanding the role of abscisic acid (ABA) and sucrose in fruit ripening, the mechanisms underlying the ABA and sucrose signalling pathways remain elusive. In this study, transcription factor ABA-stress-ripening (ASR), which is involved in the transduction of ABA and sucrose signalling pathways, was isolated and analysed in the nonclimacteric fruit, strawberry and the climacteric fruit, tomato. We have identified four ASR isoforms in tomato and one in strawberry. All ASR sequences contained the ABA stress- and ripening-induced proteins and water-deficit stress-induced proteins (ABA/WDS) domain and all ASR transcripts showed increased expression during fruit development. The expression of the ASR gene was influenced not only by sucrose and ABA, but also by jasmonic acid (JA) and indole-3-acetic acid (IAA), and these four factors were correlated with each other during fruit development. ASR bound the hexose transporter (HT) promoter, which contained a sugar box that activated downstream gene expression. Overexpression of the ASR gene promoted fruit softening and ripening, whereas RNA interference delayed fruit ripening, as well as affected fruit physiological changes. Change in ASR gene expression influenced the expression of several ripening-related genes such as CHS, CHI, F3H, DFR, ANS, UFGT, PG, PL, EXP1/2, XET16, Cel1/2 and PME. Taken together, this study may provide new evidence on the important role of ASR in cross-signalling between ABA and sucrose to regulate tomato and strawberry fruit ripening. The findings of this study also provide new insights into the regulatory mechanism underlying fruit development.

Uromodulin (UMOD) is the most abundant protein secreted in urine and the mutated form of the UMOD gene is associated with UMOD-associated kidney disease (UAKD). Although UMOD accumulates in the kidney of UAKD patients, it is unclear whether this also occurred in the chronic kidney disease (CKD) patients. Therefore, the association of single-nucleotide polymorphisms (SNPs) in the promoter region of UMOD gene with the kidney survival time of CKD was investigated. The promoter region of the UMOD gene was sequenced for 111 CKD patients. The Kaplan-Meier method was used to identify the disease outcome associated with SNPs in the promoter region of the UMOD gene in CKD patients. The Cox proportional hazard model was used to identify risk factors for the kidney survival time of CKD. SNPs in reference to GenBank accession NG-000016 were detected at 23 sites of the 481-bp in the UMOD promoter region from the CKD patients and the healthy controls. The 6 SNPs with minor allele frequency >5% in the CKD patients or controls were used for disease risk and outcome analysis. The frequent allele rs13333226AA was associated with a shorter period of kidney survival time in CKD patients (P=0.005). The length of kidney survival time in CKD patients with the rs13333226AA genotype was significantly shorter than that of patients with the frequent allele rs13333226AG+GG (relative risk, 0.361; 95% confidence interval, 0.171-0.761; P=0.007). In conclusion, analysis of genetic polymorphisms in UMOD may help to identify the CKD patient subgroups at a high risk for a disease outcome, thereby helping to refine therapeutic decisions in CKD patients.

Cardiovascular disease is the leading cause of death in chronic kidney disease. Extracellular matrix remodeling is implicated in atherosclerosis development. This study investigated the effects and possible mechanism of type I collagen expression on radial artery elasticity in patients with end-stage renal disease (ESRD).Sixty-five patients receiving forearm arteriovenous fistula in the Fourth Hospital of Hebei Medical University from January 2010 to December 2012 were enrolled in the study. The echo-tracking technique was used to measure radial artery 1-point pulse wave velocity (PWVβ), and immunohistochemical staining was used to detect the expression of type I collagen and transcription factor CBFA1, a marker for calcification, in the radial artery. Uremic serum and serum from healthy volunteers of different concentrations were then used to treat the rat aortic vascular smooth muscle cells (VSMCs), reverse transcription polymerase chain reaction (PCR) was used to measure COL1A1 and CBFA1 transcription and a Western blot was performed to detect type I collagen expression in the rat aortic VSMCs.In patients with ESRD, increased COL1A1 expression was an independent risk factor for radial artery PWVβ (P0.05) and was positively associated with that of CBFA1 (r = 0.573, P0.001). In the rat aortic VSMCs, serum from patients with ESRD upregulated COL1A1 and CBFA1 transcription as well as type I collagen expression in a concentration-dependent manner (P0.05).Type I collagen expression is an essential factor for radial artery elasticity dysfunction in patients with ESRD. Uremic toxins apparently induced a phenotypic transition of the rat aortic VSMCs, leading to increased type I collagen secretion and subsequent extracellular matrix remodeling.

Vascular calcification, a common complication in patients with chronic kidney disease, involves a variety of mechanisms associated with the regulation of calcification-associated factors. Previous clinical studies have indicated that magnesium is involved in the reduction of vascular calcification; however, the mechanism underlying this process remains unknown. The aim of the present study was to investigate the effects of magnesium on β-glycerophosphate (β-GP)-induced calcification and the underlying mechanisms. Primary rat vascular smooth muscle cells (VSMCs) were exposed to 10 mM β-GP in medium with or without the addition of 3 mM magnesium or 2-aminoethoxy-diphenylborate (2-APB; an inhibitor of magnesium transport), for a 14-day period. Calcium deposition and alkaline phosphatase (ALP) activity were measured by Alizarin red staining, quantification of calcium and enzyme-linked immunosorbent assay. The expression levels of core-binding factor α-1 (Cbfα1), matrix Gla protein (MGP) and osteopontin (OPN) were determined by reverse transcription-polymerase chain reaction or western blot analysis, following incubation for 0, 3, 6, 10 and 14 days with the different media. VSMC calcification and ALP activity was reduced significantly in the high-magnesium medium compared with the calcification medium, during the 14-day incubation. The magnesium-induced changes in the VSMCs included a β-GP-induced downregulation of Cbfα1 by day 3 of incubation, an effect that was gradually enhanced over the 14-day period. By contrast, magnesium produced notable increases in MGP and OPN expression levels, with an opposite pattern to that observed in the Cbfα1 expression levels. However, the addition of 2-APB appeared to inhibit the protective effect of magnesium on the VSMCs. Therefore, magnesium was able to effectively reduce β-GP-induced calcification in rat VSMCs by regulating the expression levels of calcification-associated factors in a time-dependent manner.

Grapevine autophagy-related genes (ARGs) include 35 members that have unique evolutionary backgrounds and expression patterns, with some of them responding to abiotic stresses, including copper stress. Autophagy is one of the most crucial self-regulating phenomena in livings organisms, including animals, plants, yeasts, etc. In the genomes of plants, like Arabidopsis, rice, tobacco, and barley, more than 30 autophagy-related genes (ARGs) have been found. These ARGs are involved in plant development, programed cell death, and the stress response process. In plants, and particularly in grapevine, high copper stress results from the application of the Bordeaux mixture, a widely used fungicide. However, the function of autophagy in plant tolerance to copper stress is unknown. Accordingly, in this study, a genome-wide analysis was performed to identify Vitis vinifera ARGs (VvARGs), and 35 VvARGs were detected. A gene family analysis revealed that the tandem and segmental duplication events played significant roles in the VvARG gene family expansion. Moreover, there was more intense signature of purifying selection for the comparison between grape and rice than between grape and Arabidopsis. In response to copper treatment, both the autophagosome number and malondialdehyde concentration increased during the initial 4 h post-treatment, and reached maximal values at 24 h. An expression analysis indicated that most VvARGs responded to copper stress at 4 h post-treatment, and some VvARGs (e.g., VvATG6, VvATG8i, and VvATG18h) exhibited responses to most abiotic stresses. These results provide a detailed overview of the ARGs in grapevine and indicate multiple functions of autophagy in fruit development and abiotic stresses in grapevine. The key ARG (e.g., ATG8i) should be investigated in more detail in grapevine and other plant species.

Background: The mitochondrial displacement loop (D-loop) is known to accumulate mutations and single nucleotide polymorphisms (SNPs) at a higher frequency than other regions of mitochondrial DNA (mtDNA). Methods: This is a case–control study. We sequenced SNPs in the D-loop of mtDNA and investigated their association with the risk of chronic kidney disease (CKD). Results: A total of 144 SNPs referring to the positions of the Revised Cambridge Reference Sequence (rCRS) for mitochondrial genome were identified in a case–control study. The minor alleles of nucleotides 73G, 146C, 150T, 194T, 195C and 310C were associated with an increased risk for CKD patients. Conclusion: Analysis of genetic polymorphisms in the mitochondrial D-loop can help identify the people who are at a high risk of developing chronic kidney disease. These SNPs can be considered as potential predictors for CKD.

Chronic kidney disease related mineral and bone disease (CKD-MBD) is a worldwide challenge in hemodialysis patients. In china, the number of dialysis patients is growing but few data are available about their bone disorders. In the current study, we aimed to evaluate the effect of clinical factors on the serum phosphorus clearance in the 80 maintenance hemodialysis (MHD) patients. Six clinical factors were identified for their association with the serum phosphorus clearance using the analysis of Spearman’s single linear correlation, including predialysis serum phosphate level, CRR, membrane surface area of the dialyzer, effective blood flow rate, the blood chamber volume, and hematocrit. In an overall multivariate analysis, pre-P, CRR, membrane SA, and Qb were identified as independent risk factors associated with the serum phosphorus clearance. In conclusion, HD could effectively clear serum phosphorus. The analysis of CRR might help to estimate serum phosphorus reduction ratio.

MicroRNAs (miRNAs), as an important growth regulator, are also involved in gibberellic acid (GA) signaling, revealing much relationship between miRNAs and GA in various plant responses. Grape is highly sensitive to GA3, which plays a significant regulatory role in regulation of flower development, berry expansion, berry set, berry ripening, and seedlessness induction; further, it was found that grapevine miR061 (VvmiR061) is a GA3 responsive miRNA. In this study, grapevine REV (VvREV) and HOX32 (VvHOX32), two target genes of VvmiR061, were predicted, verified, and cloned; homologous conservation was analyzed in various plants. The expression profiles of both VvmiR061 and its target genes (VvREV and VvHOX32) under GA3 treatment were detected by qRT-PCR during grapevine flower and berry development. Results revealed that GA3 treatment has upregulated the transcription of VvREV and VvHOX32, while it downregulated the expression of VvmiR061. The function of VvmiR061 in cleaving target genes VvREV and VvHOX32 was diminished by GA3 treatment during flower developmental process. The results of this study exhibited the importance of VvmiR061 in regulating flower development and GA3 signaling pathway and also contributed some to the knowledge of small RNA-mediated regulation in grape.

Recent studies have indicated that extracellular acid stimulation inhibited the calcification of vascular smooth muscle cells (VSMCs). Cell apoptosis played an important role in the occurrence and development of vascular calcification. We further explored the effects of Gas6/Axl or PI3K/Akt signaling pathway on the inhibition of rat VSMCs calcification in response to extracellular acid stimulation. Our study demonstrated that a high concentration of phosphorus induced apoptosis and calcification of VSMCs, decreased expression of Axl, and reduced phosphorylation of Akt. Stimulation of extracellular acid counteracted the effects as above by increasing the expression of Axl and Akt phosphorylation and decreasing the expression of activated Caspase3, which thereby decreased cell apoptosis and calcification. Moreover, the effects can be attenuated by PI3K inhibitor. Our study proved that extracellular acid stimulation played a vital role in the inhibition of rat VSMCs calcification and apoptosis in Gas6/Axl or PI3K/Akt signaling pathway.

Vascular calcification (VC) caused by chronic kidney disease (CKD)-mineral and bone disorder is a common complication of CKD. Recent studies have demonstrated that menaquinone-4 (MK-4) is negativly associated with VC in patients with CKD. Furthermore, we have previously shown that runt-related transcription factor 2 (Runx2) is important in the phenotypic transformation process of rat vascular smooth muscle cells (VSMCs), which is the key step for the development of VC. The present study investigated the influence of MK-4 on the phenotypic transformation process of rat VSMCs in order to illustrate its role in the process of VC. Calcification assays were perfomed to access the calcified degree of rat VSMCs. Additionally, the genes and proteins related to phenotypic transformation were measured by reverse transcription-polymerase chain reaction and western blotting methods. It was revealed that calcium deposition in the cells was evidently increased with an addition of β-glycerophosphate (β-GP) and could be completely prevented by co-incubation with MK-4 in a dose-dependent manner. Furthermore, the expression of Runx2 in the β-GP-induced VSMCs was inhibited by MK-4. It was also revealed that the expression of SMAD1 and bone morphogenetic protein (BMP)-2 were decreased in the β-GP-induced VSMCs treated with MK-4 in a dose-dependent manner; however, the expression of SMAD7 was increased in the β-GP-induced VSMCs treated with MK-4 in a dose-dependent manner. These observations suggest that MK-4 reduces mineralization by regulating the BMP-2 signaling pathway in order to attenuate the expression of Runx2.

Phosphorus removal from wastewater is of great importance. In the present study, ferric chloride was selected as the coagulant, and tannic acid (TA), a natural polymer, as the coagulant aid to develop an effective coagulation process with the emphasis of phosphorus recovery from different types of wastewater. The results showed that TA can accelerate the settling speed by forming flocs with large size, reduce the residual Fe(III) to eliminate the yellow color caused by Fe(III), and slightly increase the phosphorus removal efficiency. The precipitate formed by TA-aided coagulation showed the advantage of releasing phosphorus faster than ferric phosphate, indicating the possibility of phosphorus recovery from wastewater as slow release fertilizer. To further understand the structural characteristics of the precipitate, analytical techniques such as Raman spectroscopy, X-ray photoelectron spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry were employed. The analytical results indicated that TA-Fe-P complex was formed during the coagulation/flocculation processes. Solid phase in the precipitate consisted of TA-Fe-P complex, Fe-TA complex and/or ferric hydroxyphosphate.

To explore risk factors for coronary artery calcification (CAC) inpatients with end-stage renal disease (ESRD).A total of 53 ESRD patients undergoing regular hemodialysis (3 times a week) from August 2014 to March 2015 in the Fourth Hospital of Hebei Medical University were enrolled in the study. The patients were divided into the negative control group (13 cases) and three positive groups (11 mild calcification cases, 12 moderate calcification cases and 17 severe calcification cases) based on coronary artery calcification score (CACs). Clinical data of all patients at study entry were collected. Arterial blood samples were also collected at the start of the first hemodialysis (HD) session of the week to measure the levels of serum albumin, uric acid, calcium (Ca), phosphorus (P), magnesium, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), C reactive protein (CRP), beta-2 microglobulin (β2-MG), free parathyroid hormone (iPTH), alkaline phosphatase, fibrinogen, hemoglobin (HGB) and ferritin. Meanwhile, levels of blood pH were detected after collecting pre- and post-HD blood samples to calculate ΔpH (post-HD pH subtracted pre-HD pH). Logistic regression analysis was performed to analyze the correlation of CACs with clinical data and previously-reported blood biochemical indicators, followed by analysis of the incidence of CAC and influential factors in ESRD patients.Severity of CAC was positively correlated with age (r=0.269), HD duration (r=0.341), serum calcium (r=0.358), serum phosphorus (r=0.186) and pre-HD pH (r=0.275), but negatively correlated with serum albumin (r=-0.192) and ΔpH (r=-0.302), all P0.05. Logistic regression analysis revealed that age, HD duration, serum phosphorus level and ΔpH were independent risk factors for CAC in ESRD patients (P0.05). In CAC positive groups, CAC was predominantly involved in the left anterior descending artery (P0.05, P0.01 and P0.01 in mild, moderate and severe calcification group, respectively).CAC in ESRD patients seems to be affected by multiple factors, such as age, HD duration, serum phosphorus level and ΔpH. Moreover, ΔpH affects CAC mainly by pre-HD pH. Furthermore, left anterior descending artery is predominantly affected by CAC in ESRD patients.

Proceeding to illumina sequencing, determining RNA integrity numbers for poly RNA were separated from each of the four developmental stages of cv. Summer Black leaves by using Illumina HiSeq™ 2000. The sums of 272,941,656 reads were generated from vitis vinifera leaf at four different developmental stages, with more than 27 billion nucleotides of the sequence data. At each growth stage, RNA samples were indexed through unique nucleic acid identifiers and sequenced. KEGG annotation results depicted that the highest number of transcripts in 2,963 (2Avs4A) followed by 1Avs4A (2,920), and 3Avs4A (2,294) out of 15,614 (71%) transcripts were recorded. In comparison, a total of 1,532 transcripts were annotated in GOs, including Cellular component, with the highest number in "Cell part" 251 out of 353 transcripts (71.1%), followed by intracellular organelle 163 out of 353 transcripts (46.2%), while in molecular function and metabolic process 375 out of 525 (71.4%) transcripts, multicellular organism process 40 out of 525 (7.6%) transcripts in biological process were most common in 1Avs2A. While in case of 1Avs3A, cell part 476 out of 662 transcripts (71.9%), and membrane-bounded organelle 263 out of 662 transcripts (39.7%) were recorded in Cellular component. In the grapevine transcriptome, during the initial stages of leaf development 1Avs2A showed single transcript was down-regulated and none of them were up-regulated. While in comparison of 1A to 3A showed one up-regulated (photosystem II reaction center protein C) and one down regulated (conserved gene of unknown function) transcripts, during the hormone regulating pathway namely SAUR-like auxin-responsive protein family having 2 up-regulated and 7 down-regulated transcripts, phytochrome-associated protein showed 1 up-regulated and 9 down-regulated transcripts, whereas genes associated with the Leucine-rich repeat protein kinase family protein showed 7 up-regulated and 1 down-regulated transcript, meanwhile Auxin Resistant 2 has single up-regulated transcript in second developmental stage, although 3 were down-regulated at lateral growth stages (3A and 4A). In the present study, 489 secondary metabolic pathways related genes were identified during leaf growth, which mainly includes alkaloid (40), anthocyanins (21), Diterpenoid (144), Monoterpenoid (90) and Flavonoids (93). Quantitative real-time PCR was applied to validate 10 differentially expressed transcripts patterns from flower, leaf and fruit metabolic pathways at different growth stages.

Uromodulin (UMOD) is the most abundant protein secreted in urine and the mutated form of the UMOD gene is associated with UMOD-associated kidney disease (UAKD). Although UMOD accumulates in the kidney of UAKD patients, it is unclear whether this also occurred in the chronic kidney disease (CKD) patients. Therefore, the association of single-nucleotide polymorphisms (SNPs) in the promoter region of UMOD gene with the kidney survival time of CKD was investigated. The promoter region of the UMOD gene was sequenced for 111 CKD patients. The Kaplan-Meier method was used to identify the disease outcome associated with SNPs in the promoter region of the UMOD gene in CKD patients. The Cox proportional hazard model was used to identify risk factors for the kidney survival time of CKD. SNPs in reference to GenBank accession NG-000016 were detected at 23 sites of the 481-bp in the UMOD promoter region from the CKD patients and the healthy controls. The 6 SNPs with minor allele frequency >5% in the CKD patients or controls were used for disease risk and outcome analysis. The frequent allele rs13333226AA was associated with a shorter period of kidney survival time in CKD patients (P=0.005). The length of kidney survival time in CKD patients with the rs13333226AA genotype was significantly shorter than that of patients with the frequent allele rs13333226AG+GG (relative risk, 0.361; 95% confidence interval, 0.171–0.761; P=0.007). In conclusion, analysis of genetic polymorphisms in UMOD may help to identify the CKD patient subgroups at a high risk for a disease outcome, thereby helping to refine therapeutic decisions in CKD patients.

Vascular calcification (VC), in which high serum phosphate plays a critical role, is one major problem in patients with chronic kidney disease. Clinical studies report that magnesium has a protective effect on VC. However, the studies regarding the impact of high serum magnesium on VC at a cellular level are few and require further investigation. Therefore, the present study explored the effect of magnesium on calcification induced by β-glycerophosphate (BGP) in rat aortic vascular smooth muscle cells (RAVSMCs). In the present study, the addition of magnesium decreased calcium deposition, which was increased by BGP. Higher magnesium levels inhibited BGP-induced alkaline phosphatase (ALP) activity and decreased the expression of core-binding factor α-1 (Cbfα1). In conclusion, higher magnesium levels prevented BGP-induced calcification in RAVSMCs and inhibited the expression of Cbfα1 and ALP. Thus, magnesium is influencing the expression of Cbfα1 and ALP associated with VC and may have the potential to serve as a role for VC in clinical situations.

Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been described in various types of cancers and might be associated with cancer risk and disease outcome. We identified 14 SNPs with a frequency higher than 5% and 5 SNPs associated with the risk of renal cell carcinoma (RCC) in a case–control study previously. In the present study, we assessed the relationship of these SNPs and the outcome of RCC patients, a SNP of 262C/T was identified by the log-rank test for statistically significant prediction of RCC survival. In an overall multivariate analysis, allele 262 was identified as an independent predictor of RCC outcome. The length of survival of patients with 262T was significantly shorter than that of patients with allele 262C (relative risk, 2.136, 95%CI, 1.863–2.449; p = 0.000). The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify patients subgroup at high risk of a poor disease outcome.

The mitochondrial displacement loop (D-loop) is known to accumulate mutations and SNPs at a higher frequency than other regions of mitochondrial DNA (mtDNA). We had identified chronic kidney disease (CKD) risk-associated SNPs in the D-loop of CKD patients previously. In this study, we investigated the association of SNPs in the D-loop of mtDNA with the kidney survival of CKD.The D-loop region of mtDNA was sequenced for 119 CKD patients from the inpatient of the Fourth Hospital of Hebei Medical University. The Kaplan-Meier method was used to identify disease outcome-associated SNPs in the D-loop of CKD patients. The Cox proportional hazards model was used to identify risk factors for the kidney survival of CKD.In the present study, we identified 20 SNPs with a frequency higher than 5% and assessed the relationship of these SNPs with kidney survival time in CKD patients, a SNP of 146 was identified by log-rank test for statistically significant prediction of the kidney survival time. In an overall multivariate analysis, allele 146 was identified as an independent predictor of kidney survival time in CKD patients. The survival time of kidney in the CKD patients with 146C was significantly shorter than that of kidney in CKD patients with 146T (relative risk, 2.336; 95% CI, 1.319-3.923; p = 0.001).SNPs in the D-loop can predict the kidney survival of CKD patients. Analysis of genetic polymorphisms in the mitochondrial D-loop can help to identify CKD patient subgroup at high risk of a poor disease outcome.

The receptor tyrosine kinase, ephrin type-A receptor 2 (EphA2), is normally expressed at sites of cell-to-cell contact in adult epithelial tissues, however, recent studies have shown that it is also overexpressed in various types of epithelial carcinomas, with the greatest level of EphA2 expression observed in metastatic lesions. In the present study, the association between the expression of EphA2 and the outcome of RCC patients was assessed. The high expression level of EphA2 was identified by log-rank test for a statistically significant prediction of the RCC outcome. In an overall multivariate analysis, the high expression level of EphA2 was identified as an independent predictor of RCC outcome. The length of survival of the patients with high EphA2 expression was shorter than that of the patients with a low level of expression (relative risk, 2.304; 95% CI, 1.102–4.818; P=0.027). The analysis of the expression levels of EphA2 in tumor tissues may aid in the identification of the patient subgroup that are at a high risk of a poor disease outcome.

The accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been described in various types of cancers, and their association with cancer risk and disease outcome has been extensively identified. In the present study, we investigated the association between age-at-onset and SNPs in the mitochondrial D-loop using a population-based series of renal cell carcinoma(RCC). The SNP sites of nucleotides 16293A/G were identified for their association with age-at-onset using the log-rank test. The age-at-onset of patients with the minor allele G genotype was significantly lower than that of patients with the A genotype at the 16293 site (p < 0.001). Genetic polymorphisms in the D-loop are predictive markers of age-at-onset in RCC patients. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop may help identify RCC patient subgroups at high risk of early onset.

The accumulation of single-nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) may be associated with an increased cancer risk. In this case-control study, the SNPs in the mitochondrial D-loop of renal cell carcinoma (RCC) patients were identified and their association with cancer risk was evaluated. The minor alleles of nucleotides 16293A/G, 262A/G and 488T/C were associated with an increased risk, whereas the minor alleles of nucleotides 16298T/C and 16319G/A were associated with a decreased risk for RCC. Moreover, the nucleotides 16293, 262, 16298 and 16319 were identified as specifically associated with the risk of clear cell RCC (ccRCC), whereas 262 and 488 were specifically associated with papillary RCC and renal oncocytoma. In conclusion, SNPs in mtDNA are potential modifiers of RCC. The analysis of genetic polymorphisms in the mitochondrial D-loop may help identify the patient subgroups at a high risk of developing RCC.