Chiral TPE Foldamers in Macrocycles: Aggregation Enhanced Emission and Circularly Polarized Luminescence.

Chiral macrocycles with circularly polarized luminescence (CPL) have attracted increasing attention due to the rigid structure, symmetrical chiral geometry and large luminescence dissymmetry factors (glum ). However, most chiral macrocycles are more emissive in solutions but have weakened fluorescence quantum yields (ΦF ) in aggregates, limiting their further application. In this paper, chiral macrocycle R/S-PhTPE was synthesized by combining chiral macrocycle architectonics with Z-o-phenyltetraphenylethylene (PhTPE) foldamer. Enhanced solution state emission and characteristic aggregation enhanced emission (AEE) effect can be observed for R/S-PhTPE due to the folded PhTPE conformation. Macrocycle immobilization and folded conformation endow PhTPE moiety with stable helical conformation. Most importantly, R/S-PhTPE exhibits opposite CPL signals compared with common chiral TPEs, demonstrating the evident impact of folded conformation. This work reports the first and deep insights into the chiroptical properties of chiral PhTPE foldamers, and will provide a new strategy to tune ΦF and CPL signals of AIE active chiral macrocycles.

Genome-wide association study of the candidate genes for grape berry shape-related traits.

BACKGROUND: In the breeding of new horticultural crops, fruit shape is an important selection characteristic. A variety of fruit shapes appeared during the gradual process of selection and domestication. However, few studies have been conducted on grape berry shape, especially studies related to mining candidate genes. To discover candidate genes related to grape berry shape, the present study first took the berry shape parameters analyzed by Tomato Analyzer as the target traits and used a genome-wide association analysis to analyze candidate genes. RESULTS: In total, 122 single-nucleotide polymorphism (SNP) loci had significant correlations with multiple berry shape traits in both years, and some candidate genes were further mined. These genes were mainly related to LRR receptor-like serine/threonine-protein kinase (At1g05700 and At1g07650), transcription factors (GATA transcription factor 23-like, transcription factor VIP1, transcription initiation factor TFIID, and MADS-box transcription factor 6), ubiquitin ligases (F-box protein SKIP19 and RING finger protein 44), and plant hormones (indole-3-acetic acid-amido synthetase GH3.6 and ethylene-responsive transcription factor ERF061). In addition, some important SNP loci were associated with multiple berry-shape traits. The study further revealed some genes that control multiple traits simultaneously, indicating that these berry shape traits are subject to the coordinated regulation of some genes in controlling berry shape. CONCLUSIONS: In the present work, we identified interesting genetic determinants of grape berry shape-related traits. The identification of molecular markers that are closely related to these berry-shape traits is of great significance for breeding specific berry-shaped grape varieties.

Genome-wide analysis of autophagy-related genes (ARGs) in grapevine and plant tolerance to copper stress.

MAIN CONCLUSION: 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.

Prediction task guided representation learning of medical codes in EHR.

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.

Extracellular acidosis suppresses calcification of vascular smooth muscle cells by inhibiting calcium influx via L-type calcium channels.

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) ß3 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 ß-GP. The expression of Runx2 and ALP activity markedly rose, accompanied by the increasing expression of LTCC ß3 subunits and calcium influx. However, acidosis supplementation successfully attenuated VC and VSMC calcification and inhibited Runx2, ALP, LTCC ß3 subunits, and calcium influx. In conclusion, acidosis significantly attenuated vascular calcification in association with downregulation of the LTCC/Ca2+/Runx2 pathway.

Characterization of miR061 and its target genes in grapevine responding to exogenous gibberellic acid.

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.

Abscisic acid and sucrose regulate tomato and strawberry fruit ripening through the abscisic acid-stress-ripening transcription factor.

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.

Effects of extracellular acid stimulation on rat vascular smooth muscle cell in Gas6/Axl or PI3K/Akt signaling pathway.

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.

Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA is associated with the kidney survival time in chronic kidney disease patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[Risk factors for coronary artery calcification in patients with end-stage renal disease].

OBJECTIVE: To explore risk factors for coronary artery calcification (CAC) inpatients with end-stage renal disease (ESRD). METHODS: 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 (ß2-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. RESULTS: 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 P<0.05. Logistic regression analysis revealed that age, HD duration, serum phosphorus level and ΔpH were independent risk factors for CAC in ESRD patients (P<0.05). In CAC positive groups, CAC was predominantly involved in the left anterior descending artery (P<0.05, P<0.01 and P<0.01 in mild, moderate and severe calcification group, respectively). CONCLUSIONS: 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.

Association of sequence polymorphism in the mitochondrial D-loop with chronic kidney disease.

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.

Positive response of a hemodialysis patient with pure red cell aplasia on recombinant human erythropoietin therapy to cyclosporine and Roxadustat.

Recombinant human erythropoietin (rHuEPO) is commonly used to treat anemia associated with chronic kidney disease (CKD). EPO-induced Pure Red Cell Aplasia (PRCA) is a rare condition of profound anemia with EPO treatment. Upon finding the development of EPO-induced PRCA, the treatment requires immediate withdrawal of EPO therapy and initiate new treatments with immunosuppression or renal transplantation. Anti-EPO antibody assay is not always positive in EPO-induced PRCA. Here, we report a case on the sudden development of PRCA in a hemodialysis patient receiving EPO and how we treated the condition successfully with cyclosporine and subsequently maintained the hemoglobin with Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). Even though the anti-EPO antibody was negative by Enzyme Linked Immunosorbent Assay (ELISA) in our case, the clinical course, the markedly reduced reticulocyte count < 10,000/µL, the bone marrow (BM) biopsy revealing reduced erythroblasts, and its subsequent response to cyclosporine, were similar to EPO-induced PRCA. The clinical picture of EPO-induced PRCA, the limitation of the EPO-neutralizing antibody (Ab) assay, and treatment strategies were discussed.

Meticulous catheter care and aseptic approach reduce catheter-related bloodstream infections significantly in hemodialysis patients: A 5-year single center study.

AIM: The use of central venous catheters as hemodialysis vascular access is a major contributor to high bloodstream infection rate. In our dialysis unit in Shenzhen Guangdong Province China, we have developed and used our own dialysis catheter care protocol since May 2013 with good results. In this study, we would like to share our experience with the other units. METHODS: We have undertaken a 5-year retrospective analysis to determine our tunneled dialysis catheter-related blood stream infection rate by adding the number of infections divided by total number of catheter days × 1000. The results were compared with another study carried out in Henan Province China. Demographic data were summarized using descriptive statistics. Continuous and categorical variables were compared using t-test and χ2 test respectively. RESULTS: Between 2017 and 2021, a total of 216 tunneled dialysis catheters were managed by following our own dialysis access pathway and catheter care protocol. The tunneled dialysis catheter-related bloodstream infection rate was 0.0229 per 1000 catheter days in the 5-year period. CONCLUSION: Comparing with other published studies in China, our unit has achieved a very low rate of tunneled dialysis catheter-related bloodstream infection which has been sustained over time. This paper explores how our protocol and implementation might have contributed to the results.

Spraying Zinc Sulfate to Reveal the Mechanism through the Glutathione Metabolic Pathway Regulates the Cadmium Tolerance of Seashore Paspalum (Paspalum vaginatum Swartz).

Cadmium (Cd) is considered to be one of the most toxic metals, causing serious harm to plants' growth and humans' health. Therefore, it is necessary to study simple, practical, and environmentally friendly methods to reduce its toxicity. Until now, people have applied zinc sulfate to improve the Cd tolerance of plants. However, related studies have mainly focused on physiological and biochemical aspects, with a lack of in-depth molecular mechanism research. In this study, we sprayed high (40 mM) and low (2.5 mM) concentrations of zinc sulfate on seashore paspalum (Paspalum vaginatum Swartz) plants under 0.5 mM Cd stress. Transcriptome sequencing and physiological indicators were used to reveal the mechanism of Cd tolerance. Compared with the control treatment, we found that zinc sulfate decreased the content of Cd2+ by 57.03-73.39%, and that the transfer coefficient of Cd decreased by 58.91-75.25% in different parts of plants. In addition, our results indicate that the antioxidant capacity of plants was improved, with marked increases in the glutathione content and the activity levels of glutathione reductase (GR), glutathione S-transferase (GST), and other enzymes. Transcriptome sequencing showed that the differentially expressed genes in both the 0.5 Zn and 40 Zn treatments were mainly genes encoding GST. This study suggests that genes encoding GST in the glutathione pathway may play an important role in regulating the Cd tolerance of seashore paspalum. Furthermore, the present study provides a theoretical reference for the regulation mechanism caused by zinc sulfate spraying to improve plants' Cd tolerance.

Chiral cyclic architectonics with tetraphenylethylenes: conformation immobilization, optical resolution and circularly polarized luminescence.

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 (Z/E)-isomerism and helical chirality of TPE. The chiral cyclic TPEs can emit deep blue circularly polarized luminescence (CPL) in both solution and film states.

Relationship of serum copper and zinc with kidney function and urinary albumin to creatinine ratio: Cross-sectional data from the NHANES 2011-2016.

BACKGROUND & OBJECTIVE: 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. METHODS: 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 m2 and increased urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g. RESULTS: Findings 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 level <18.0 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. CONCLUSIONS: 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.

Transcriptome and metabolite profiling reveal that spraying calcium fertilizer reduces grape berry cracking by modulating the flavonoid biosynthetic metabolic pathway.

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.

The diagnostic effect of α-defensin, D-dimer, and IL-6 in periprosthetic joint infection: A systematic review and diagnostic meta-analysis.

BACKGROUND: Periprosthetic joint infection (PJI) is the most common complication after artificial joint replacement as previously reported. However, the main problem at present is its difficulty in diagnosis. This systematic review and meta-analysis aimed to compare the diagnostic accuracy of α-defensin, D-dimer, and interleukin-6 (IL-6) in clinical practice. METHOD: Online databases were systematically searched until June 18th, 2020 with keywords and medical sub-headings terms. Studies mentioned the sensitivity and specificity of biological markers in detecting PJI were included in our study. The sensitivity, specificity, and diagnostic odds ratios (DORs) were obtained after integration. RESULTS: A total of 34 studies with 1036 patients diagnosing as PJI were included for comparing α-defensin, D-dimer, and IL-6. The sensitivity and specificity of α-defensin for PJI were 0.88 and 0.96, and the DOR was 189 (95% CI 72-496), respectively. The sensitivity and specificity of D-dimer (0.82 and 0.72) and IL-6 (0.80 and 0.89) were lower than α-defensin. CONCLUSION: The detection of α-defensin is a promising biomarker for diagnosing PJI. The optional cut-off needs to be curtained when using other biomarkers.

Enhanced coagulation of ferric chloride aided by tannic acid for phosphorus removal from wastewater.

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.

Menaquinone-4 modulates the expression levels of calcification-associated factors to inhibit calcification of rat aortic vascular smooth muscle cells in a dose-dependent manner.

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 ß-glycerophosphate (ß-GP) and could be completely prevented by co-incubation with MK-4 in a dose-dependent manner. Furthermore, the expression of Runx2 in the ß-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 ß-GP-induced VSMCs treated with MK-4 in a dose-dependent manner; however, the expression of SMAD7 was increased in the ß-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.