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The development of cracks in reinforced concrete structures can accelerate structural deterioration and reduce service life. A numerical model was established to analyse steel bar corrosion in chloride-contaminated concrete with transverse cracks. In the model, the dynamic distinction between anode and cathode regions on the steel surface is considered by introducing an empirical formula for the anodic Tafel slope related to chloride concentration. The time-dependent characteristics of the corroded region were examined using the proposed corrosion prediction model and the corrosion process of steel bars in cracked concrete was revealed. The effects of crack width and crack spacing on steel corrosion were analysed in detail in terms of the corrosion area and corrosion rate. The results showed a variation in the corrosion area adjacent to cracks over time and a positive correlation between corrosion area and the square root of time. According to the micro-cell and macro-cell contributions to the corrosion rate, the process of steel bar corrosion was determined to occur in three stages. The effects of transverse cracks on the corrosion rate were found to vary with exposure time and to depend on the control steps of the micro- or macro-cells.

Introduction/objectivesTo seek significant features of systemic lupus erythematosus (SLE) by utilizing bioinformatics analysis.MethodLiquid chromatography-tandem mass spectrometry (LC–MS/MS) was used to quantify lysine crotonylation (Kcr) and lysine 2-hydroxyisobutyrylation (Khib) in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients and normal controls.ResultsSeventy-six differentially modified proteins (DMPs) dually modified by Kcr and Khib were identified between SLE patients and healthy people. GO enrichment analysis prompted significant enrichment of seventy-six DMPs in MHC class II protein complex binding and leukocyte migration. KEGG pathways were enriched in antigen processing and presentation pathway and leukocyte transendothelial migration pathway. Six DMPs (CLTC, HSPA1B, HSPA8, HSP90AB1, HSPD1, and PDIA3) were identified in antigen processing and presentation pathway, of which HSPA8 was the core protein. Significant changes of Kcr and Khib in HSPA8 may increase ATP hydrolysis and promote antigen binding to MHC II molecule. In leukocyte transendothelial migration pathway, 7 DMPs (ACTN1, ACTN4, EZR, MSN, RAC1, RHOA, and VCL) were identified. MSN was the protein with the most modification sites in this pathway. In amino terminal ferm region of MSN, Kcr and Khib expression change may lead to the adhesion between leukocytes and endothelial cells, which was an important step of leukocyte migration.ConclusionKcr and Khib may promote the antigen presentation and jointly regulate the tissue damage mediated by leukocyte migration in SLE patients, which may play key roles in the pathogenesis of SLE probably.Key Points• Antigen processing and presentation and leukocyte transendothelial migration may play key roles in the pathogenesis of SLE.

The construction of advanced metering infrastructure and the rapid evolution of artificial intelligence bring opportunities to quickly search for the optimal dispatching strategy for reactive power optimization by mining existing prior knowledge and massive data without explicitly constructing physical models. Therefore, a novel data-driven-based approach is proposed for reactive power optimization of distribution networks using capsule networks (CapsNet). The convolutional layers with strong feature extraction ability are used to project the power loads to the feature space to realize the automatic extraction of key features. Furthermore, the complex relationship between input features and dispatching strategies is captured accurately by capsule layers. The back propagation algorithm is utilized to complete the training process of the CapsNet. Case studies show that the accuracy and robustness of the CapsNet are better than those of popular baselines (e.g., convolutional neural network, multi-layer perceptron and case-based reasoning). Besides, the computing time is much lower than the traditional heuristic methods, such as genetic algorithm, which can meet the real-time demand of reactive power optimization in distribution networks.

Cisplatin is an effective chemotherapeutic agent in facilitating the inhibition of proliferation, migration, and invasion in cancerous cells. However, the detailed mechanism of the regulation by cisplatin of human breast cancer cells is still unclear. This study aimed to investigate the mechanism of kruppel-like factor 2 (KLF2) transcription factor in cisplatin therapy for breast cancer. RT-qPCR was performed to quantify the expression of KLF2 and WEE1 in clinical tissue samples from breast cancer patients and in MDA-MB-231 cells. ChIP assay and dual-luciferase reporter assay were used to analyze the potential-binding sites of KLF2 and WEE1 promoter. Gain- or loss-of-function approaches were used to manipulate KLF2 and WEE1 in cisplatin-treated MDA-MB-231 cells, and the mechanism of KLF2 in breast cancer was evaluated both via CCK-8 assay, flow cytometry, Transwell assay, and Western blot. Further validation of the KLF2 was performed on nude mouse models. Breast cancer tissues and cells showed a relative decline of KLF2 expression and abundant WEE1 expression. Cisplatin inhibited the proliferation, migration, and invasion of MDA-MB-231 cells. Overexpression of KLF2 enhanced the inhibitory effect of cisplatin on the malignant characteristics of MDA-MB-231 cells in vitro. KLF2 targeted WEE1 and negatively regulated its expression, thus enhancing the sensitivity to cisplatin of breast cancer cells as well as tumor-bearing mice. Overall, these results suggest that KLF2 can potentially inhibit WEE1 expression and sensitize breast cancer cells to cisplatin, thus presenting a promising adjunct treatment.

Introduction. The modification of lysine crotonylation (Kcr) is another biological function of histone in addition to modification of lysine acetylation (Kac), which may play a specific regulatory role in diseases. Objectives. This study compared the expression levels of Kcr and proteome between patients with chronic obstructive pulmonary disease (COPD) combined with type II respiratory failure (RF) to study the relationship between Kcr, proteome, and COPD. Methods. We tested the Kcr and proteome of COPD combined with type II RF and normal control (NC) using croton acylation enrichment technology and liquid chromatography tandem mass spectrometry (LC-MS/MS) with high resolution. Results. We found that 32 sites of 23 proteins were upregulated and 914 sites of 295 proteins were downregulated. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG), protein domain, and Gene Ontology (GO) analysis on crotonylated protein. In proteomics research, we found that 190 proteins were upregulated and 151 proteins were downregulated. Among them, 90 proteins were both modified by differentially expressed crotonylation sites and differentially expressed in COPD combined with type II RF and NC. Conclusion. Differentially expressed crotonylation sites may be involved in the development of COPD combined with type II RF. 90 proteins modified by crotonylation and differentially expressed in COPD combined with type II RF can be used as markers for the study of the molecular pathogenesis of COPD combined with type II RF.

Background Trisomy 18 syndrome (Edwards syndrome, ES) is a type of aneuploidy caused by the presence of an extra chromosome 18. Aneuploidy is the leading cause of early pregnancy loss, intellectual disability, and multiple congenital anomalies. The research of trisomy 18 is progressing slowly, and the molecular characteristics of the disease mechanism and phenotype are still largely unclear. Results In this study, we used the commercial Chromium platform (10× Genomics) to perform sc-ATAC-seq to measure chromatin accessibility in 11,611 single umbilical cord blood cells derived from one trisomy 18 syndrome patient and one healthy donor. We obtained 13 distinct major clusters of cells and identified them as 6 human umbilical cord blood mononuclear cell types using analysis tool. Compared with the NC group, the ES group had a lower ratio of T cells to NK cells, the ratio of monocytes/DC cell population did not change significantly, and the ratio of B cell nuclear progenitor and megakaryocyte erythroid cells was higher. The differential genes of ME-0 are enriched in Human T cell leukemia virus 1 infection pathway, and the differential peak genes of ME-1 are enriched in apopotosis pathway. We found that CCNB2 and MCM3 may be vital to the development of trisomy 18. CCNB2 and MCM3, which have been reported to be essential components of the cell cycle and chromatin. Conclusions We have identified 6 cell populations in cord blood. Disorder in megakaryocyte erythroid cells implicates trisomy 18 in perturbing fetal hematopoiesis. We identified a pathway in which the master differential regulatory pathway in the ME-0 cell population involves human T cell leukemia virus 1 infection, a pathway that is dysregulated in patients with trisomy 18 and which may increase the risk of leukemia in patients with trisomy 18. CCNB2 and MCM3 in progenitor may be vital to the development of trisomy 18. CCNB2 and MCM3, which have been reported to be essential components of the cell cycle and chromatin, may be related to chromosomal abnormalities in trisomy 18.

A water freeze-thaw cycle and sulfate freeze-thaw coupling cycle were explored experimentally to evaluate the durability of recycled concrete with lithium slag (LS). The damage-deterioration law was studied from the aspects of mass-change rate, relative dynamic modulus of elasticity, and cube’s compressive strength. Based on the relative dynamic modulus of elasticity, the damage-degree equation of the concrete was fitted, and a mechanical-attenuation model related to this parameter and the cube’s compressive strength was established and verified. The damage mechanism under the action of the sulfate freeze-thaw cycle was revealed through scanning electron microscopy (SEM). The combination of recycled coarse aggregate (RCA) and LS was beneficial to the anti-deterioration ability of the concrete. During the cycle experiments, the mass and relative dynamic modulus of elasticity increased initially and then decreased, while the cube’s compressive strength declined continually. The concrete with a 30 % RCA substitution rate and 20 % LS exhibited the optimal comprehensive durability, and specimens with excessive LS showed more susceptibility to sulfate erosion. The residual compressive strength of concrete structures can be evaluated by measuring the relative dynamic modulus of elasticity as the two parameters are ideally correlated.

In this study, a new electrochemical aptasensor with specific identification and quantitative analysis of glypican-3 (GPC3) was constructed using reduced graphene oxide-chitosan-ferrocene deposition of Pt–Pd bimetallic nanoparticles (RGO-CS-Fc/Pt–Pd BNPs) as biosensing platform and GPC3 aptamer (GPC3apt) as recognition molecule. The GPC3apt could react specifically with GPC3 present in the experimental samples, resulting in the formation of GPC3-aptamer complexes on the biosensing platform, which would increase the electron transfer impedance and reduce the redox current of ferrocene. The electrochemical aptasensor was characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV), electrochemical impedance spectrometry (EIS), and Raman spectroscopy. Under the optimal experimental conditions, the response redox current was linearly related to the concentration of GPC3 in the range from 0.001 to 10 µg mL−1 with good linear correlation coefficient (R2 of 0.9929), and had a low detection limit of 3.67 ng mL−1 (S/N = 3), high sensitivity of 0.149 µA µM−1 cm−2. In addition, the aptasensor showed long stability, good specificity, acceptable reproducibility and satisfactory recoveries (101.1–105.6%) in the detection of clinical serum samples, which developed a new research method for early clinical diagnosis.

Glypican-3 (GPC3) is a potential hepatocellular carcinoma (HCC) serum marker with good sensitivity and specificity. Herein, a label-free electrochemical aptasensor for the detection of GPC3 was developed using a reduced graphene oxide–hemin–chitosan (RGO–H–CS) nanocomposite-modified screen-printed electrode (SPE) as a biosensing platform and GPC3 aptamer as the recognition element. When GPC3 was present, the aptamer could specifically bind with the target GPC3 by specific recognition reaction and form GPC3–aptamer conjugations on the sensing surface, which could alter the electrochemical redox signal of hemin (Fe(III)/hemin(Fe(II))) in the RGO–H–CS nanocomposite recorded by differential pulse voltammetry (DPV). The electrochemical GPC3 aptasensor was characterized via scanning electron microscopy (SEM), Raman spectroscopy, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Under optimal conditions, currents originating from the oxidation of hemin had a linear relationship with the concentration of GPC3 in the range of 0.01 µg mL−1 to 10.0 µg mL−1 with a detection limit of 7.9 ng mL−1 (S/N = 3). The developed aptasensor was applied to detect the GPC3 level in the human serum samples with the recovery rate of 101.04–104.9%. Moreover, the label-free aptasensor exhibited considerable anti-interfering ability, acceptable stability and good reproducibility. Therefore, this study provides a reliable and objective analysis method to achieve high screening for the early diagnosis of HCC.

The under-deposit corrosion behavior and mechanism of aluminum brass (HAl77-2) were investigated in artificial seawater with a custom double electrolytic cell. The experiments included linear polarization, electrochemical impedance spectroscopy, and multielectrode arrays analysis. The electrochemical results revealed a pronounced effect of temperature on the under-deposit corrosion behavior of HAl77-2. The corrosion of HAl77-2 inside the CaCO3 scale is aggravated with increasing temperature. However, the increasing frequency of the corrosion rate of HAl77-2 gradually decreased after 333 K. Moreover, in the desalination of artificial seawater, the corrosion rate of HAl77-2 in the occulated area initially increased and subsequently decreased with increasing Cl− concentration. The scanning electron microscopy and energy dispersive spectrometry analysis showed a remarkable appearance of selective localized corrosion on the surface of HAl77-2.

Transplantation is currently the best treatment for patients with end-stage renal disease. However, acute rejection (AR) is the major source of failure in renal transplantation. The current best practice for the diagnosis of AR involves renal biopsy, but it is invasive, time-consuming, costly and inconvenient. Sensitive and less invasive detection of AR episodes in renal transplant patients is essential to preserve allograft function. The present study applied isobaric tags for relative and absolute quantitation (iTRAQ) mass spectrometry to analyze serum protein expression in patients with AR and healthy controls. Overall, 1,399 proteins were identified. Using a cut-off of Q1.2 for the variation in expression, 109 proteins were identified to be differentially expressed between the AR and control groups, 72 of which were upregulated and 37 were downregulated. Several proteins, including properdin, keratin 1, lipoprotein(a) and vitamin D-binding protein, may have roles in the pathogenesis of AR. The present study focused on iTRAQ-based proteomic profiling of serum samples in AR. Insight from the present study may help advance the understanding of the molecular mechanisms of AR and identify potential novel biomarkers of AR for further characterization.

Posttranslational modifications (PTMs) to histones such as lysine crotonylation are classified as epigenetic changes. Lysine crotonylation participates in various cellular processes and occurs in active promoters, directly accelerating transcription. The present study performed a proteomics analysis of crotonylation between healthy controls and patients with immunoglobulin A (IgA) nephropathy using tandem mass spectrometry and high‑resolution liquid chromatography. The present results identified 353 crotonylated proteins and 770 modification sites, including 155 upregulated and 198 downregulated crotonylated proteins. In total, seven conserved motifs were identified in the present study. The present bioinformatics analysis results suggested a number of the crotonylated proteins exhibited various subcellular localization patterns, such as in the cytoplasm. Protein domains, including thioredoxin, moesin tail and myosin like IQ motif domains were markedly enriched in crotonylated proteins. Kyoto Encyclopedia of Genes and Genomes and functional enrichment analyses suggested significant enrichment of crotonylated proteins in complement and coagulation cascades, and antigen processing and presentation pathways displaying important relationships with IgA nephropathy. The present results suggested that crotonylation occurred in numerous proteins and may play key regulatory roles in IgA nephropathy.

TOX high mobility group box family member 3 (TOX3) can function as tumor suppressor or oncogene in different tumors, while ras homolog family member B (RhoB) is a well-known tumor suppressor. The expression and role of TOX3 in colorectal cancer (CRC) are unknown. This study aimed to investigate the expression of TOX3 in CRC and the role of TOX3/mitogen-activated protein kinase (MAPK)/RhoB signaling in the proliferation and apoptosis of CRC cells. We showed that TOX3 messenger RNA (mRNA) and protein expression levels were significantly upregulated in CRC tissues and cell lines. High TOX3 expression was associated with high T stage, nodal invasion, and advanced tumor stage. Disease-free survival (DFS) was shortened for CRC patients with high expression of TOX3, while overall survival showed no significant difference. TOX3 promoted proliferation, inhibited apoptosis, and decreased the sensitivity to oxaliplatin of CRC cells. In addition, the inhibition of TOX3 led to the upregulation of RhoB, and RhoB overexpression suppressed the proliferation and promoted apoptosis of CRC cells. Moreover, TOX3 overexpression upregulated MAPK signaling, while MAPK signaling inhibitor U0126 induced CRC cell proliferation arrest or apoptosis, and attenuated the inhibition of RhoB in TOX3 overexpression cells. In addition, the overexpression of TOX3 increased tumor volume in nude mice. In conclusion, TOX3 may be an oncogene in CRC and can predict DFS in CRC patients. TOX3/MAPK/RhoB signaling plays an important role in the modulation of proliferation and apoptosis of CRC cells.

Ultra-high performance geopolymer concrete (UHPGC) has been favored due to its excellent sustainability and outstanding mechanical properties. This study was conducted to explore the mechanical and durability properties of slag/metakaolin-based UHPGC with steel fibers reinforcement. The uniaxial compression test and rapid chloride migration test were conducted to measure the compressive strength and chloride penetration resistance of UHPGC. A total of nine groups of mixture proportions were designed and tested to investigate the influences of steel fiber dosage and sodium hydroxide (NaOH) solution concentration. The results showed that an increased steel fiber dosage and alkali concentration can improve compressive strength, and the maximum compressive strength can reach more than 140 MPa. In addition, the rapid chloride migration test showed that the chloride penetration resistance of the slag/metakaolin-based concrete was moderate, with a non-steady chloride migration coefficient ranging from 6.5 × 10−12 m2/s to 14.1 × 10−12 m2/s. The increase in steel fiber volume content slightly enlarged chloride penetration depth, while the higher concentration of sodium hydroxide solution was beneficial as it improved chloride penetration resistance. The results suggest that although ultra-high compressive strength can be achieved, the durability issues of steel fiber reinforced slag/metakaolin-based geopolymer concrete still need considerable attention.

Background Autosomal dominant osteopetrosis type II (ADO2) is a rare human genetic disease that has been broadly studied as an important osteopetrosis model; however, there are no disease-specific induced pluripotent stem cells (ADO2-iPSCs) that may be valuable for understanding the pathogenesis and may be a potential source of cells for autologous cell-based therapies. Methods To generate the first human ADO2-iPSCs from a Chinese family with ADO2 and to identify their characteristics, blood samples were collected from the proband and his parents and were used for genotyping by whole-exome sequencing (WES); the urine-derived cells of the proband were reprogrammed with episomal plasmids that contained transcription factors, such as KLF4, OCT4, c-MYC, and SOX2. The proteome-wide protein quantification and lysine 2-hydroxyisobutyrylation detection of the ADO2-iPSCs and normal control iPSCs (NC-iPSCs) were performed by high-resolution LC-MS/MS and bioinformatics analysis. Results WES with filtering strategies identified a mutation in CLCN7 (R286W) in the proband and his father, which was absent in the proband’s mother and the healthy controls; this was confirmed by Sanger sequencing. The ADO2-iPSCs were successfully generated, which carried a normal male karyotype (46, XY) and the mutation of CLCN7 (R286W); the ADO2-iPSCs positively expressed alkaline phosphatase and other surface markers; and no vector and transgene were detected. The ADO2-iPSCs could differentiate into all three germ cell layers, both in vitro and in vivo. The proteomic profiling revealed similar expression of pluripotency markers in the two cell lines and identified 7405 proteins and 3664 2-hydroxyisobutyrylated peptides in 1036 proteins in the ADO2-iPSCs. Conclusions Our data indicated that the mutation CLCN7 (R286W) may be a cause of the osteopetrosis family. The generated vector-free and transgene-free ADO2-iPSCs with known proteomic characteristics may be valuable for personalized and cell-based regenerative medicine in the future. Electronic supplementary material The online version of this article (10.1186/s13287-019-1369-8) contains supplementary material, which is available to authorized users.

The morbidity and mortality associated with acute kidney injury (AKI) remain obstinately high. Early diagnosis is urgently required and should be pursued in at-risk populations. Recently, a newly validated biomarker, matrix metalloproteinase-7 (MMP-7), was reported as a novel indicator for early AKI prediction and a noninvasive surrogate biomarker of kidney function. Monitoring urinary MMP-7 (uMMP-7) levels fills the gaps in early diagnosis of AKI at early onset. However, the lack of available reagents for its rapid detection limits its use. Herein, we established an ultrasensitive and rapid immunomagnetic microparticles-based time-resolved fluoroimmunoassay to measure urinary MMP-7 in AKI patients. The assay time is 30 min. The calibration curve showed high linear correlation (r = 0.9998) with a linearity of detection of 0.063–150 ng mL−1 and lower limit of detection of 0.039 ng mL−1. The coefficient variation of the intra- and inter-assay lower than 5.17%, and the analytical recovery was 99.06%–105.60%. Testing of clinical samples using the proposed assay and a DUOSET@ ELISA kit showed good correlations in the comparison of uMMP-7 levels (r = 0.9541) and uMMP-7/uCreatinine (r = 0.9595). The proposed assay has satisfactory analytical performance and may serve as a promising tool for early diagnosis of AKI.

Background: Chromosome 22q11.2 deletion (CH22qD) syndrome is the most common human deletion syndrome. Competing endogenous RNAs (ceRNAs) have miRNA binding sites that are capable of competitively binding miRNAs and inhibiting miRNA regulation of target genes. Results: We identified differently expressed miRNAs, circRNAs, lncRNAs and mRNAs of CH22qD, and we analysed the results by using GO analysis, KEGG pathway analysis and network regulation analysis. Conclusions: These analyses may predict the effects of chromosomal microdeletions.

Background: IgA nephropathy (IgAN) is one of the most common forms of primary glomerulonephritis. Recent studies have indicated that small noncoding RNAs, such as tRNA-derived small RNAs (tsRNAs), might be novel biomarkers for glomerulonephritis. We therefore investigated the potential roles and possible functions of the tsRNAs in IgAN. Method: Peripheral blood mononuclear cells (PBMCs) were extracted from blood samples of the patients with IgAN and healthy control groups. The expression profiles of tsRNAs were assessed by small RNA sequencing (RNA-Seq) in PBMCs of the IgAN and control groups. Dysregulated tsRNAs were selected for validation by quantitative real-time polymerase chain reaction (qRT-PCR). Target gene prediction and enrichment were performed by bioinformatics analysis. Results: The results revealed that 143 significantly upregulated and 202 significantly downregulated tsRNAs were differentially altered in the IgAN group compared with the control group. Five upregulated tsRNAs (tRF-Val-AAC-007, tRF-Ala-AGC-063, tRF-Gln-CTG-010, tRF-Tyr-GTA-011 and tRF-Thr-AGT-007) and 3 downregulated tsRNAs (tiRNA-Val-TAC-004, tRF-Gly-CCC-005 and tRF-His-GTG-006) were selected for validation by qRT-PCR; the results were consistent with the sequencing data. Gene Ontology (GO) analysis revealed that the target genes predicted by upregulated tsRNAs were mostly enriched in “nucleic acid metabolic process," “intracellular part," and “ion binding," whereas the target genes predicted by downregulated tsRNAs were mostly enriched in “regulation of cellular component organization," “membrane-bound organelle," and “ion binding." Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes predicted by upregulated tsRNAs were mostly enriched in “herpes simplex virus 1 infection," whereas the target genes predicted by downregulated tsRNAs were mostly enriched in “circadian rhythm Conclusions: The present study confirmed the differential expression of tsRNAs in patients with IgAN, and these dysregulated tsRNAs might be novel potential targets for the diagnosis and treatment of IgAN.

Objective: LncRNAs are a class of competing for endogenous RNAs (ceRNAs) with no coding ability and have miRNA binding sites that competitively bind to miRNAs and inhibit miRNA-mediated regulation of target genes. In recent years, an increasing number of studies have recognized the biological functions of lncRNAs.Methods: Illumina RNA-Seq technology was used to analyze the cord blood with Patau syndrome (PS) fetal and the peripheral blood of pregnant women to obtain differential expression profiles of lncRNAs, miRNAs, and mRNAs. Further, Combined with bioinformatics analysis of the biological functions of differentially expressed lncRNAs (DElncRNAs). Results: The results showed that 467 DElncRNAs, 8512 differentially expressed mRNAs (DEmRNAs), and 18 differentially expressed miRNAs (DEmiRNAs) were found to be co-expressed in cord blood and peripheral blood. The hsa-miR-15a-5p is located on chromosome 13. We constructed the ceRNA network with hsa-miR-15a-5p, lncRNAs as the bait, and mRNAs as the targe. Conclusion: We consider that the DElncRNAs may indirectly regulate the target gene CLASRP or KARS by binding hsa-miR-15a-5p to participate in the occurrence of PS.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organs, the pathogenic mechanism is related to many factors, but the specific pathogenic mechanism has not been clarified yet. Protein lysine modifications play important roles in gene regulation, transcription, metabolism and other biological processes. The lysine 2-hydroxyisobutyrylation(K hib ) histone mark has recently been discovered as a novel protein modification. In this study, patients in the active SLE group were examined (N=8), while the control group was healthy (N=20).Utilizing antibody-based affinity enrichment and nano-HPLC/MS/MS analyses of K hib peptides, we identified 156 upregulated proteins(fold change>1.5),124 downregulated proteins(fold change

The aim of this study was to identify novel genetic variants affecting tacrolimus trough blood concentrations. We analyzed the association between 58 single nucleotide polymorphisms (SNPs) across the CYP3A gene cluster and the log-transformed tacrolimus concentration/dose ratio (log (C0/D)) in 819 renal transplant recipients (Discovery cohort). Multivariate linear regression was used to test for associations between tacrolimus log (C0/D) and clinical factors. Luciferase reporter gene assays were used to evaluate the functions of select SNPs. Associations of putative functional SNPs with log (C0/D) were further tested in 631 renal transplant recipients (Replication cohort). Nine SNPs were significantly associated with tacrolimus log (C0/D) after adjustment for CYP3A5*3 and clinical factors. Dual luciferase reporter assays indicated that the rs4646450 G allele and rs3823812 T allele were significantly associated with increased normalized luciferase activity ratios (p

Liver cirrhosis of hepatitis B is an immune-related disease in which liver cells die during the body’s immune system activation to clear the virus, and the progress is closely related to T lymphocytes. T lymphocyte cells recognise antigens, specifically by major histocompatibility complex (MHC), through a membrane protein T cell receptor (TCR). Here, we used high throughput immune repertoire sequencing technique to study the characteristics and diversity of the TCR repertoire between patients who underwent liver transplantation and healthy controls (NC). We sequenced the TCR β-chain complementary-determining region 3 (CDR3) repertoire in peripheral blood mononuclear cells (PBMCs) from 6 liver transplantation patients before transplantation (Pre) and on the first (Post1) and seventh days (Post7) after transplantation along with 6 NC. We observed that the distributions of CDR3, VD indel, and DJ indel lengths were similar among the Pre, Post1, Post7 and NC groups. We found that the TCR repertoire diversity of transplantation groups was relatively lower compared to NC group. The Pre-group had more highly expanded T cell clones compared to Post1, Post7 and NC groups, and the diversity of the T cell repertoire of the Post7 group was significantly decreased compared to the Pre, Post1 and NC groups. In addition, we found our results also show that various TRBV expression increased and some public sequences at different time points after liver transplantation, and the expression levels of 3 TRBV segments and 2 TRBJ segments were also significantly different in Pre, Post1, Post7 and NC groups. Moreover, 1 aa sequence shared by all liver transplantation patients and 2 aa sequences shared by at least two groups, which may serve as biomarkers to monitor the immune status of liver transplant patients.

Recent studies have shown that circular RNAs (circRNAs) exhibit differential expression in certain diseases. However, to the best of our knowledge, maternal fetal-derived circRNAs and mRNAs associated with Down's syndrome (DS) have not yet been investigated. A total of 12 umbilical cord blood samples were collected from pregnant women, including six women carrying fetuses with DS (diagnosed by G-banding karyotype analysis), and six women carrying fetuses without DS. In addition, 12 peripheral blood samples were obtained from children, including six children with DS and six children without DS. Gene chip technology was used to screen for differentially expressed circRNAs and mRNAs in the cord blood samples, and were subsequently verified by reverse transcription-quantitative polymerase chain reaction in peripheral blood from the children to identify potential biomarkers. Furthermore, circRNA/microRNA (miRNA) interactions were predicted using Arraystar miRNA target prediction software. There was a significant difference in the expression of hsa_circRNA_103127, hsa_circRNA_103112 and hsa_circRNA_104907 between cord blood obtained from the women carrying fetuses with and without DS, and between peripheral blood obtained from children with and without DS (P

Early diagnosis of diabetes yields significant clinical benefits. The serum level of 1,5‑anhydroglucitol (1,5‑AG) has been a new biochemical marker for postprandial hyperglycemia. In this study, a simple colorimetric method for 1,5‑AG detection has been designed based on highly efficient peroxidase mimetic activity of GQDs and enzyme-catalyzed reaction. By the catalytic action of pyranose oxidase (PROD), the 1,5‑AG was oxidized to 1,5‑anhydrofuctose and H2O2. The GQDs in the presence of H2O2 exhibited highly efficient catalytic activity toward the oxidation of 3, 3', 5, 5'‑tetramethylbenzidine (TMB) to a blue colored product. The influence of relevant experimental variables was optimized. A linear relationship of optical signal with the concentration of 1,5‑AG in the range of 20.0-100.0μg/mL with the regression correlation coefficient of 0.9985 was obtained which could be monitored by colorimetry detection. The limit of detection (LOD) for 1,5‑AG detection was approximately 0.144μg/mL. All in all, the proposed 1,5‑AG detection system based on GQDs and PROD-catalyzed reaction showed better performances with simple operation, low-cost, higher selectivity.

The aim of the present study was to screen gastric cancer (GC) tissue and adjacent tissue for differences in mRNA and circular (circRNA) expression, to analyze the differences in circRNA and mRNA expression, and to investigate the circRNA expression in gastric carcinoma and its mechanism. circRNA and mRNA differential expression profiles generated using Agilent microarray technology were analyzed in the GC tissues and adjacent tissues. qRT-PCR was used to verify the differential expression of circRNAs and mRNAs according to the interactions between circRNAs and miRNAs as well as the possible existence of miRNA and mRNA interactions. We found that: i) the circRNA expression profile revealed 1,285 significant differences in circRNA expression, with circRNA expression downregulated in 594 samples and upregulated in 691 samples via interactions with miRNAs. The qRT-PCR validation experiments showed that hsa_circRNA_400071, hsa_circRNA_000543 and hsa_circRNA_001959 expression was consistent with the microarray analysis results. ii) 29,112 genes were found in the GC tissues and adjacent tissues, including 5,460 differentially expressed genes. Among them, 2,390 differentially expressed genes were upregulated and 3,070 genes were downregulated. Gene Ontology (GO) analysis of the differentially expressed genes revealed these genes involved in biological process classification, cellular component classification and molecular function classification. Pathway analysis of the differentially expressed genes identified 83 significantly enriched genes, including 28 upregulated genes and 55 downregulated genes. iii) 69 differentially expressed circRNAs were found that might adsorb specific miRNAs to regulate the expression of their target gene mRNAs. The conclusions are: i) differentially expressed circRNAs had corresponding miRNA binding sites. These circRNAs regulated the expression of target genes through interactions with miRNAs and might become new molecular biomarkers for GC in the future. ii) Differentially expressed genes may be involved in the occurrence of GC via a variety of mechanisms. iii) CD44, CXXC5, MYH9, MALAT1 and other genes may have important implications for the occurrence and development of GC through the regulation, interaction, and mutual influence of circRNA-miRNA-mRNA via different mechanisms.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies that is closely associated with the Hepatitis B virus (HBV). HBV integration into host genomes can induce instability and the aberrant expression of human genomic DNA. To directly assess HBV integration breakpoints at whole genome level, four small sequencing libraries were constructed and the HBV integration profiles of four patients with HCC were characterized. In total, the current study identified 11,800,974, 11,216,998, 11,026,546 and 11,607,842 clean reads for patients 1-3 and 4, respectively, of which 92.82, 95.95, 97.21 and 97.29% were properly aligned to the hybrid reference genome. In addition, 220 HBV integration events were detected from the tumor tissues of four patients with HCC and an average of 55 breakpoints per sample was calculated. The results indicated that HBV integration events may be implicated in HCC physiologies and diseases. The results acquired may also provide insight into the pathogenesis of HCC, which may be valuable for future HCC therapy.

Using recycled coarse aggregate (RCA) to replace natural pebbles and using lithium slag (LS) from industrial waste to replace cement in order to improve the mechanical properties of concrete and solve environmental problems. In this study, the effects of different substitution rates of RCA (0, 30%, 50%, and 70%) and different LS contents (0, 10%, 15%, 20%, and 25%) on the mechanical properties of concrete were investigated. The main results indicate that when the substitution rate of RCA is 30% and the LS content is 20%, optimal cube compressive strength, axial compressive strength, and elastic modulus can be achieved, with an increase of 9.90%, 48.22%, and 9.94% respectively; when the substitution rate of RCA is 70% and the LS content is 20%, the splitting tensile strength and flexural strength can be improved by 9.90% and 48.22%, respectively. The morphology of RCA concrete specimens with LS was observed with a scanning electron microscope (SEM). Moreover, corrections were made to improve the relevant formula according to the differences between the measured intensity index and data converted from current specifications.

Full proteomic analysis methods. (DOCX 21 kb)

Down syndrome (DS) is caused by trisomy of human chromosome 21 and is associated with a number of deleterious phenotypes. To investigate the role of microRNA (miRNA) in the regulation of DS, high-throughput Illumina sequencing technology and isobaric tagging for relative and absolute protein quantification analysis were utilized for simultaneous expression profiling of miRNA and protein in fetuses with DS and normal fetuses. A total of 344 miRNAs were associated with DS. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to investigate the proteins found to be differentially expressed. Functionally important miRNAs were determined by identifying enriched or depleted targets in the transcript and the protein expression levels were consistent with miRNA regulation. The results indicated that GRB2, TMSB10, RUVBL2, the hsa-miR-329 and hsa-miR-27b, hsa-miR-27a targets, and MAPK1, PTPN11, ACTA2 and PTK2 or other differentially expressed proteins were connected with each other directly or indirectly. Integrative analysis of miRNAs and proteins provided an expansive view of the molecular signaling pathways in DS.