Transcriptome-wide RNA m6A methylation profiles in an endemic osteoarthropathy, Kashin-Beck disease.

Kashin-Beck disease (KBD) is a chronic degenerative, disabling disease of the bones and joints and its exact aetiology and pathogenesis remain uncertain. This study is to investigate the role of m6A modification in the pathogenesis of KBD. Combined analysis of m6A MeRIP-Seq and RNA-Seq were used to analyse human peripheral blood samples from three KBD patients and three normal controls (NC). Bioinformatic methods were used to analyse m6A-modified differential genes and RT-qPCR was performed to validate the mRNA expression of several KBD-related genes. The results indicated that the total of 16,811 genes were modified by m6A in KBD group, of which 4882 genes were differential genes. A large number of differential genes were associated with regulation of transcription, signal transduction and protein binding. KEGG analysis showed that m6A-enriched genes participated the pathways of Vitamin B6 metabolism, endocytosis and Rap 1 signalling pathway. There was a positive association between m6A abundance and levels of gene expression, that there were 6 hypermethylated and upregulated genes (hyper-up), 23 hypomethylated and downregulated genes (hypo-down) in KBD group compared with NC. In addition, the mRNA expression of levels of MMP8, IL32 and GPX1 were verified and the protein-protein interaction networks of these key factors were constructed. Our study showed that m6A modifications may play a vital role in modulating gene expression, which represents a new clue to reveal the pathogenesis of KBD.

Plasma metabolites and inflammatory proteins profiling predict outcome of Fufang Duzhong Jiangu granules treating Kashin-Beck disease.

To investigate predictive biomarkers that could be used to identify patients' response to treatment, plasma metabolomics and proteomics analyses were performed in Kashin-Beck disease (KBD) patients treated with Fufang Duzhong Jiangu Granules (FDJG). Plasma was collected from 12 KBD patients before treatment and 1 month after FDJG treatment. LC-MS and olink proteomics were employed for obtaining plasma metabolomics profiling and inflammatory protein profiles. Patients were classified into responders and non-responders based on drug efficacy. Enrichment analyses of differential metabolites and proteins of the responders at baseline and after treatment were conducted to study the mechanism of drug action. Differential metabolites and proteins between the two groups were screened as biomarkers to predict the drug efficacy. The receiver operating characteristic curve was used to evaluate the prediction accuracy of biomarkers. The changes in metabolites and inflammatory proteins in responders after treatment reflected the mechanism of FDJG treatment for KBD, which may act on glycerophospholipid metabolism, d-glutamine and d-glutamate metabolism, nitrogen metabolism and NF-kappa B signaling pathway. Three metabolites were identified as potential predictors: N-undecanoylglycine, ß-aminopropionitrile and PC [18:3(6Z,9Z,12Z)/20:4(8Z,11Z,14Z,17Z)]. For inflammatory protein, interleukin-8 was identified as a predictive biomarker to detect responders. Combined use of these four biomarkers had high predictive ability (area under the curve = 0.972).

Evaluating the interactive effects of dietary habits and human gut microbiome on the risks of depression and anxiety.

BACKGROUND: Gut microbiome and dietary patterns have been suggested to be associated with depression/anxiety. However, limited effort has been made to explore the effects of possible interactions between diet and microbiome on the risks of depression and anxiety. METHODS: Using the latest genome-wide association studies findings in gut microbiome and dietary habits, polygenic risk scores (PRSs) analysis of gut microbiome and dietary habits was conducted in the UK Biobank cohort. Logistic/linear regression models were applied for evaluating the associations for gut microbiome-PRS, dietary habits-PRS, and their interactions with depression/anxiety status and Patient Health Questionnaire (PHQ-9)/Generalized Anxiety Disorder-7 (GAD-7) score by R software. RESULTS: We observed 51 common diet-gut microbiome interactions shared by both PHQ score and depression status, such as overall beef intake × genus Sporobacter [hurdle binary (HB)] (PPHQ = 7.88 × 10-4, Pdepression status = 5.86 × 10-4); carbohydrate × genus Lactococcus (HB) (PPHQ = 0.0295, Pdepression status = 0.0150). We detected 41 common diet-gut microbiome interactions shared by GAD score and anxiety status, such as sugar × genus Parasutterella (rank normal transformed) (PGAD = 5.15 × 10-3, Panxiety status = 0.0347); tablespoons of raw vegetables per day × family Coriobacteriaceae (HB) (PGAD = 6.02 × 10-4, Panxiety status = 0.0345). Some common significant interactions shared by depression and anxiety were identified, such as overall beef intake × genus Sporobacter (HB). CONCLUSIONS: Our study results expanded our understanding of how to comprehensively consider the relationships for dietary habits-gut microbiome interactions with depression and anxiety.

A large Stokes shift NIR fluorescent probe for visual monitoring of mitochondrial peroxynitrite during inflammation and ferroptosis and in an Alzheimer's disease model.

The excessive formation of peroxynitrite (ONOO-) in mitochondria has been implicated in various pathophysiological processes and diseases. However, owing to short emission wavelengths and small Stokes shifts, previously reported fluorescent probes pose significant challenges for mitochondrial ONOO- imaging in biological systems. In this study, a near-infrared (NIR) fluorescent probe, denoted as DCO-POT, is designed for the visual monitoring of mitochondrial ONOO-, displaying a remarkable Stokes shift of 170 nm. The NIR fluorophore of DCO-CHO is released by DCO-POT upon the addition of ONOO-, resulting in off-on NIR fluorescence at 670 nm. This phenomenon facilitates the high-resolution confocal laser scanning imaging of ONOO- generated in biological systems. The practical applications of DCO-POT as an efficient fluorescence imaging tool are verified in this study. DCO-POT enables the fluorometric visualization of ONOO- in organelles, cells, and organisms. In particular, ONOO- generation is analyzed during cellular and organism-level (zebrafish) inflammation during ferroptosis and in an Alzheimer's disease mouse model. The excellent visual monitoring performance of DCO-POT in vivo makes it a promising tool for exploring the pathophysiological effects of ONOO-.

Self-Cascade Nanoenzyme of Cupric Oxide Nanoparticles (CuO NPs) Induced in Situ Catalysis Formation of Polyelectrolyte as Template for the Synthesis of Near-Infrared Fluorescent Silver Nanoclusters and the Application in Glutathione Detection and Bioimaging.

In this work, near-infrared fluorescent silver nanoclusters (Ag NCs) were prepared based on the in situ formed poly methacrylic acid (PMAA) as the template and stabilizer, which is synthesized by methacrylic acid (MAA) and hydroxyl radical (·OH) that is generated by the cascade nanoenzyme reaction of cupric oxide nanoparticles (CuO NPs). CuO NPs possess the intrinsic glutathione-like (GPx-like) and peroxidase-like (POD-like) activities, which can catalyze glutathione (GSH) and O2 to produce hydrogen peroxide (H2O2), and then transform into ·OH. The fluorescence intensity of Ag NCs decreases with the addition of GSH, because the -SH can easily anchor on the surface, resulting in the PMAA leaving the Ag NCs, and the coeffect of GSH and PMAA results in the aggregation to form larger Ag NPs. A good linear relationship between the fluorescence quenching rate and the GSH concentration was found in the range 0.01-40 µM with the detection limit 8.0 nM. The Ag NCs can be applied in the detection of GSH in the serum, as well as bioimaging of endogenous and exogenous GSH in cells with high sensitivity. Moreover, the normal and cancer cells can be distinguished through bioimaging because of the different GSH levels. The new method for the preparation of biocompatible nanoprobe based on the nanozyme tandem catalysis and the in situ formed template can avoid the direct usage of polymers or protein templates that hinder preparation and separation, providing a reliable approach for the synthesis, biosensing, and bioimaging of nanoclusters.

Associations between electronic devices use and common mental traits: A gene-environment interaction model using the UK Biobank data.

BACKGROUND: Electronic devices use has been reported to be associated with depression. However, limited effort has been provided to elucidate the associations between electronic devices use and mental traits in interaction with genetic factors. METHODS: We first conducted an observational study consisting of 138 976-383 742 participants for TV watching, 29 636-38 599 participants for computer using and 118 61-330 985 participants for computer playing in the UK Biobank cohort. A linear regression model was used to evaluate the associations between common mental traits and electronic devices use. Subsequently, a genome-wide gene-environment interaction study (GWEIS) was performed by PLINK2.0 to estimate the interaction effects of genes and electronic devices use on the risks of the four mental traits. RESULTS: In the UK Biobank cohort, significant associations were observed between electronic devices use and mental traits (all P < 1.0 × 10-9 ), including depression score (B = 0.094 for TV watching), anxiety score (B = 0.051 for TV watching), cigarette smoking (B = 0.046 for computer using) and alcohol drinking (B = 0.010 for computer playing). GWEIS identified multiple mental traits associated loci, interacting with electronic devices use, such as DCDC2 (rs115986722, P = 4.10 × 10-10 ) for anxiety score and TV watching, PRKCE (rs56181965, P = 9.64 × 10-10 ) for smoking and computer using and FRMD4A (rs56227933, P = 7.42 × 10-11 ) for depression score and computer playing. CONCLUSIONS: Our findings suggested that electronic devices use was associated with common mental traits and provided new clues for understanding genetic architecture of mental traits.

A fluorescence nanoplatform for the determination of hydrogen peroxide and adenosine triphosphate via tuning of the peroxidase-like activity of CuO nanoparticle decorated UiO-66.

A novel nanocomposite of CuO nanoparticle-modified Zr-MOF (CuO/UiO-66) was synthesized and developed as a fluorescence nanoplatform for H2O2 and adenosine triphosphate (ATP) via the "turn-on-off" mode in the presence of terephthalic acid (TA). The structure of CuO/UiO-66 was thoroughly characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), and other techniques. The CuO/UiO-66 with enhanced peroxidase-like (POD) activity obtained due to the Zr4+ in UiO-66 is beneficial to the aggregation of CuO NPs on its surface. As a result, the strengthened fluorescence at 425 nm with the excitation of 300 nm was found due to the highly fluorescent species of TAOH. This is produced by the oxidation of TA by ·OH that came from the catalysis of H2O2 via the peroxidase mimic of CuO/UiO-66. Hence the modification of CuO NPs on porous UiO-66 can provide a friendly and sensitive physiological condition for H2O2 detection. However, upon addition of ATP, the fluorescence intensity of TAOH at 425 nm effectively declined owing to the formation of complexation of Zr4+-ATP and the interaction of CuO to ATP which hampers the catalytic reaction of CuO/UiO-66 to H2O2. The specific interaction induced "inhibition of the peroxide-like activity" endows the sensitive and selective recognition of ATP. The detection limits were 16.87 ± 0.2 nM and 0.82 ± 0.1 nM, and linear analytical ranges were 0.02-100 µM and 0.002-30 µM for H2O2 and ATP, respectively. The novel strategy was successfully applied to H2O2 and ATP determination in serum samples with recoveries of 97.2-103.8% for H2O2 and 97.6-101.7% for ATP, enriching the avenue to design functional MOFs and providing new avenue of multicomponent bioanalysis.

A turn-on near-infrared fluorescent probe for visualization of endogenous alkaline phosphatase activity in living cells and zebrafish.

Alkaline phosphatase (ALP) is an essential hydrolase and widely distributed in living organisms. It plays important roles in various physiological and pathological processes. Herein, a turn-on near-infrared (NIR) fluorescent probe (DXMP) was developed for sensitive detection of ALP activity both in vitro and in vivo based on the intramolecular charge transfer (ICT) mechanism. Upon incubation with ALP, DXMP exhibited a strong fluorescence increment at 640 nm, which was attributed to the fact that ALP-catalyzed cleavage of the phosphate group in DXMP induced the transformation of DXMP into DXM-OH. The probe exhibited prominent features including outstanding selectivity, high sensitivity, and excellent biocompatibility. More importantly, it has been successfully used to detect and image endogenous ALP in living cells and zebrafish.

A Large-Scale Genetic Correlation Scan Between Intelligence and Brain Imaging Phenotypes.

Limited efforts have been paid to evaluate the potential relationships between structural and functional brain imaging and intelligence until now. We performed a two-stage analysis to systematically explore the relationships between 3144 brain image-derived phenotypes (IDPs) and intelligence. First, by integrating genome-wide association studies (GWAS) summaries data of brain IDPs and two GWAS summary datasets of intelligence, we systematically scanned the relationship between each of the 3144 brain IDPs and intelligence through linkage disequilibrium score regression (LDSC) analysis. Second, using the individual-level genotype and intelligence data of 160 124 subjects derived from UK Biobank datasets, polygenetic risk scoring (PRS) analysis was performed to replicate the common significant associations of the first stage. In the first stage, LDSC identified 6 and 2 significant brain IDPs significantly associated with intelligence dataset1 and dataset2, respectively. It is interesting that NET100_0624 showed genetic correlations with intelligence in the two datasets of intelligence. After adjusted for age and sex as the covariates, NET100_0624 (P = 5.26 × 10-20, Pearson correlation coefficients = -0.02) appeared to be associated with intelligence by PRS analysis of UK Biobank samples. Our findings may help to understand the genetic mechanisms of the effects of brain structure and function on the development of intelligence.

Integrative analysis of genome-wide association study and expression quantitative trait loci datasets identified various immune cell-related pathways for rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune chronic disorder manifesting as warm, swollen, and painful joints. Multiple immune cells are implicated in the development of RA. Previous studies demonstrated that integrating the genetic information of genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) is capable of identifying new disease-risk loci and providing novel insights into the etiology of complex human disease. In this study, we conducted an integrative pathway association analysis of RA by using GWAS summary data and five immune cell types related to eQTL datasets of RA. After combining the cell-specific eQTLs and GWAS summary of RA and performing a pathway-enrichment analysis, we detected a group of RA-associated pathways with common or cell-specific enriched in the five immune cell types. 41 pathways for B cells, 33 pathways for CD4+ T cells, 27 pathways for CD8+ T cells, 39 pathways for monocyte, and 25 pathways for natural killer cells are significant in RA, among which 48% are common pathways and 32% are cell-specific pathways. We detected a group of RA-associated eQTL pathways related to five different immune cell types. Our findings may provide novel insights into the pathogenesis of RA.

GWAS summary-based pathway analysis correcting for the genetic confounding impact of environmental exposures.

Genome-wide association study (GWAS)-based pathway association analysis is a powerful approach for the genetic studies of human complex diseases. However, the genetic confounding effects of environment exposure-related genes can decrease the accuracy of GWAS-based pathway association analysis of target diseases. In this study, we developed a pathway association analysis approach, named Mendelian randomization-based pathway enrichment analysis (MRPEA), which was capable of correcting the genetic confounding effects of environmental exposures, using the GWAS summary data of environmental exposures. After analyzing the real GWAS summary data of cardiovascular disease and cigarette smoking, we observed significantly improved performance of MRPEA compared with traditional pathway association analysis (TPAA) without adjusting for environmental exposures. Further, simulation studies found that MRPEA generally outperformed TPAA under various scenarios. We hope that MRPEA could help to fill the gap of TPAA and identify novel causal pathways for complex diseases.

Insight into the Effect of Ligands on the Optical Properties of Germanium Quantum Dots and Their Applications in Persistent Cell Imaging.

Germanium quantum dots (GeQDs) show unique advantages in fluorescence applications due to their large quantum confinement effect and excellent biocompatibility. However, GeQDs are confronted with difficulty in accurately controlling the fluorescence emission. This defect brings challenges to understanding the fluorescence mechanism and limits the potential applications of GeQDs. In this paper, a series of GeQDs with the average diameter of about 2.6 nm modified with different ligands were synthesized by the chemical reduction method. The fluorescence emission of GeQDs can be changed from blue to yellow-green through adjusting the surface ligands. The influence of surface ligands on the fluorescence emission of GeQDs was thoroughly investigated by experimental and theoretical calculations. Furthermore, the synthesized GeQDs exhibit good biocompatibility and photostability and can act as high-performance fluorescence probes for long-term fluorescent bioimaging. This work provides a good and deep understanding of the fluorescence mechanism of GeQDs and will facilitate diverse promising applications of GeQDs in the near future.

A near-infrared excitation/emission fluorescent probe for imaging of endogenous cysteine in living cells and zebrafish.

The fluorescence imaging technique provides an essential tool for studying biological systems. However, due to the interference of autofluorescence of biological tissues, the application of short-wavelength fluorescent probes in biological imaging was limited. The near-infrared (NIR) excitation/emission fluorescent probe possesses unique advantages in optical imaging in vivo, including less light scattering, minimal photo-damage to biological samples, deep tissue penetration, and weak autofluorescence interference from complicated biological systems. In this work, a convenient fluorophore (E)-2-[2-(6-hydroxy-2,3-dihydro-1H-xanthen-4-yl)vinyl]-3- methylbenzo[d]thiazol-3-ium iodide (DXM-OH) with NIR excitation and emission was rationally designed and developed. What's more, DXM-OH was applied to construct an "OFF-ON" fluorescent probe (E)-2-{2-[6-(acryloyloxy)-2,3-dihydro-1H- xanthen-4-yl]vinyl}-3-methylbenzo[d]thiazol-3-ium iodide (DXM) for sensitive and selective detection of cysteine (Cys). The experimental results showed that DXM had the advantages of good cell permeability, low toxicity, and excellent optical properties (NIR excitation/emission) and it was successfully applied to image Cys of living cells and zebrafish.

Roles of glycoprotein glycosylation in the pathogenesis of an endemic osteoarthritis, Kashin­Beck disease, and effectiveness evaluation of sodium hyaluronate treatment

Background/aim: We aimed to explore the roles of glycoprotein glycosylation in the pathogenesis of Kashin­Beck disease (KBD), and evaluated the effectiveness of sodium hyaluronate treatment. Materials and methods: Blood and saliva were collected from KBD patients before and after the injection of sodium hyaluronate. Normal healthy subjects were included as controls. Saliva and serum lectin microarrays and saliva and serum microarray verifications were used to screen and confirm the differences in lectin levels among the three groups. Results: In saliva lectin microarray, bindings to Sophora japonica agglutinin (SJA), Griffonia (Bandeiraea) simplicifolia lectin I (GSL-I), Euonymus europaeus lectin (EEL), Maackia amurensis lectin II (MAL-II), Sambucus nigra lectin (SNA), Hippeastrum hybrid lectin (HHL), and Aleuria aurantia lectin (AAL) were higher in the untreated KBD patients than in the control group. Increased levels of HHL, MAL-II, and GSL-I in the untreated KBD patients discriminated them in particular from the treated ones. Jacalin was lower in the untreated KBD patients compared to the treated KBD and control groups. In serum lectin microarray, HHL and peanut agglutinin (PNA) were increased in the untreated KBD group in comparison to the control one. AAL, Phaseolus vulgaris agglutinin (E+L) (PHA-E+L), and Psophocarpus tetragonolobus lectin I (PTL-I) were lower in the untreated KBD patients compared to the treated KBD and control groups. Hyaluronate treatment appeared to normalize SNA, AAL, and MAL-II levels in saliva, and HHL, PNA, AAL, PTL-I, and PHA-E+L levels in serum. Saliva reversed microarray verification confirmed significant differences between the groups in SNA and Jacalin, in particular for GSL-I levels, while serum reversed microarray verification indicated that HHL, PNA, and AAL levels returned to normal levels after the hyaluronate treatment. Lectin blot confirmed significant differences in HHL, AAL, and Jacalin in saliva, and HHL, PNA, PHA-E+L, and AAL in serum. Conclusion: HHL in saliva and serum may be a valuable diagnostic biomarker of KBD, and it may be used as follow-up for the hyaluronate treatment.

A dual-signal colorimetric and ratiometric fluorescent nanoprobe for enzymatic determination of uric acid by using silicon nanoparticles.

The authors describe a dual-signal colorimetric and ratiometric fluorescent probe for uric acid (UA). It is based on cascade catalysis and an inner filter effect. The method involves uricase-catalyzed oxidation of UA and iodide-catalyzed oxidation of the colorless peroxidase substrate o-phenylenediamine (OPD) to form yellow 2,3-diaminophenazine (oxOPD). This can be visually observed or monitored by measuring absorbance at 417 nm. Furthermore, oxOPD quenches the fluorescence of silicon nanoparticles (SiNPs) (with peaks at 450 and 565 nm) via an inner filter effect. The change in the ratio of emissions peaking 565 and 450 (at excitation wavelength of 380 nm) increases linearly in the 0.01-0.8 mM UA concentration range). The lower detection limits are 8.4 and 0.75 µM when using the colorimetric and ratiometric fluorometric method, respectively. The assay was successfully applied to the quantitation of UA in spiked serum samples. Graphical abstractA dual-signal colorimetric and ratiometric fluor ometric assay was developed for uric acid (UA). The fluorometric assay is based on the inner filter effect between fluorescent silicon nanoparticles and 2,3-diaminophenazine. It involves uricase-catalyzed oxidation of UA, and iodide-catalyzed oxidation of o-phenylenediamine.

A turn-on fluorescent probe for vitamin C based on the use of a silicon/CoOOH nanoparticle system.

The authors describe a fluorometric method for the turn-on determination of vitamin C (ascorbic acid). The blue fluorescence of silicon nanoparticles (SiNPs; with excitation/emission maxima at 350/450 nm) is found to be quenched by CoOOH nanoparticles (NPs). In the presence of vitamin C, the CoOOH NPs are decomposed by a redox reaction between the diol group of vitamin C and CoOOH NPs. As a result, fluorescence recovers. On the basis of this finding, a fluorometric method was designed for the turn-on detection of vitamin C. Under optimal conditions, the method has a low detection limit (0.47 µM) and a linear response in the 0.5 µM to 20 µM a concentration range. It was successfully applied to the determination of vitamin C in spiked red grape and orange juice, and in vitamin C tablets. Graphical abstract A target-triggered dissociation of quencher-based strategy for the fluorescence "turn-on" detection of vitamin C was developed. It is based on surface energy transfer (SET) and an inner filter effect (IFE) between silicon nanoparticles and CoOOH nanoparticles as well as the redox reaction between vitamin C and CoOOH nanoparticles.

Tissue-specific pathway association analysis using genome-wide association study summaries.

MOTIVATION: Pathway association analysis has made great achievements in elucidating the genetic basis of human complex diseases. However, current pathway association analysis approaches fail to consider tissue-specificity. RESULTS: We developed a tissue-specific pathway interaction enrichment analysis algorithm (TPIEA). TPIEA was applied to two large Caucasian and Chinese genome-wide association study summary datasets of bone mineral density (BMD). TPIEA identified several significant pathways for BMD [false discovery rate (FDR) < 0.05], such as KEGG FOCAL ADHESION and KEGG AXON GUIDANCE, which had been demonstrated to be involved in the development of osteoporosis. We also compared the performance of TPIEA and classical pathway enrichment analysis, and TPIEA presented improved performance in recognizing disease relevant pathways. TPIEA may help to fill the gap of classic pathway association analysis approaches by considering tissue specificity. AVAILABILITY AND IMPLEMENTATION: The online web tool of TPIEA is available at https://sourceforge.net/projects/tpieav1/files CONTACT: fzhxjtu@mail.xjtu.edu.cnSupplementary information: Supplementary data are available at Bioinformatics online.

Synthesis of Fluorescent and Water-Dispersed Germanium Nanoparticles and Their Cellular Imaging Applications.

In recent years, Ge nanomaterials have aroused a great deal of attention because of their unique physical and chemical properties. However, the current synthesis methods bear some disadvantages, such as high reaction temperature, dangerous reagents, and inert atmospheres. In this paper, we developed a facile one-step route for preparing fluorescent and water-dispersed germanium nanoparticles (Ge NPs) by utilizing organogermanes as the precursor, operated at mild reactive conditions. The as-synthesized Ge NPs have an average diameter of 2.6 ± 0.5 nm and intense blue-green fluorescence (FL). Furthermore, the as-synthesized Ge NPs show remarkable water dispersibility, favorable biocompatibility, outstanding photostability, excellent storage stability, and low cytotoxicity. More importantly, these Ge NPs can act as a satisfactory FL probe and successfully be applied to cellular imaging of HeLa. The present study offers a simple and moderate strategy for the preparation of Ge NPs and expedites Ge NPs for bioimaging applications.

Highly sensitive and selective determination of copper(II) based on a dual catalytic effect and by using silicon nanoparticles as a fluorescent probe.

The authors describe a silicon nanoparticle-based fluorometric method for sensitive and selective detection of Cu2+. It is based on the catalytic action of Cu2+ on the oxidation of cysteine (Cys) by oxygen to form cystine and the by-product H2O2. The generated H2O2 is catalytically decomposed by Cu2+ to generate hydroxyl radicals which oxidize and destroy the surface of SiNPs. As a result, the blue fluorescence of the SiNPs is quenched. The method has excellent selectivity due to the dual catalytic effects of Cu2+, which is much better than most previously reported nanomaterial-based assays for Cu2+. Under the optimal conditions, the method has low detection limit (29 nM) and a linear response in a concentration range from 0.05 µM to 15 µM. The method has been successfully applied to the determination of Cu2+ in spiked real water samples, and the results agreed well with those obtained by the Chinese National Standard method (GB/T 7475-1987; AAS). Graphical abstract Schematic presentation of a fluorometric method for the determination of Cu2+ based on the dual catalytic effects of Cu2+, and the oxidative effect of hydroxy radicals on the surface of silicon nanoparticles (SiNPs). The method has a 29 nM detection limit and good selectivity.

[The Effect of Disordered Glycometabolism of Kashin-Beck Disease on the Function of Chondrocytes].

OBJECTIVE: To reveal the effect of disordered glycometabolism in Kashin-Beck disease (KBD) chondrocytes,we compared changes in expressions of extracellular matrix components (collagen and aggrecan),apoptosis and oxidative stress under the condition of different concentrations of glucose. METHODS: The damage of KBD chondrocytes and normal chondrocytes under high glucose culture was measured in compared with cells under normal culture,that included the changes of proliferation and morphology; the concentrations of glucose in culture medium during the process of chondrocytes culture; the expressions of type Ⅱ collagen and aggrecan detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Toluidine blue staining; cell apoptosis and reactive oxygen species (ROS) content detected by flow cytometry and fluorescence staining. RESULTS: The growth and proliferation of KBD chondrocytes were inferior to normal chondrocytes. The glucose uptake of KBD chondrocytes and normal chondrocytes under high glucose culture were basically the same (P>0.05). Disordered glycometabolism caused by high glucose decreased the expression of type Ⅱ collagen and aggrecan in KBD chondrocytes (P<0.05),meanwhile,increased apoptosis and cellular ROS generation of cultured chondrocytes (P<0.05). CONCLUSION: The disordered glycometabolism can affect the function of KBD chondrocytes through reducing the expression of type Ⅱ collagen and aggrecan and increasing the apoptosis and the oxidative stress.