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Anisotropic nanomaterials, such as gold nanorods (AuNRs), could be employed as an orientation platform due to their polarization-dependent surface plasmon resonance. However, a variety of factors would affect the dark-field light scattering imaging of anisotropic nanomaterials, resulting in an unstable signal, which is not advantageous to its further application. In this work, the localized surface plasmon resonance properties of a few AuNRs at different angles were excited by polarization with a conventional dark-field microscope, in which it was found that the ratio of AuNRs' light scattering intensity at different polarization angles (

Objective To investigate if inhibitory effects of propofol on proliferation, invasion and migration of non-small cell lung carcinoma (NSCLC) cells was associated with the regulation of miR-199a/PAK4 axis. Methods Human NSCLC A549 and H1299 cells were treated with propofol of different concentrations at different time points. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to evaluate miR-199a expression. A549 and H1299 cells were divided into Control, Propofol, Propofol + miR-NC and Propofol + miR-199a inhibitor groups. The proliferation, apoptosis, migration, and invasion were examined by CCK-8, flow cytometry, wound healing, and Transwell, respectively. Western blotting was used to measure the protein expression of PAK4. Xenograft model was established in nude mice to observe if propofol can mediate miR-199a expression to regulate the growth of subcutaneous xenograft tumor. Results Propofol can effectively enhance the expression of miR-199a in NSCLC. Compared with Control group, H1299 and A549 cells in Propofol group decreased in viability, invasion and migration, and increased in apoptosis. The inhibitory effect of propofol on NSCLC growth was reversed by miR-199a. In comparison with Propofol group, Propofol + miR-199a inhibitor group was declined in miR-199a expression and increased in PAK4 protein expression. According to dual-luciferase reporter assay, PAK4 was a target gene of miR-199a. Experiment in vivo revealed propofol can inhibit the growth and reduce the weight of xenograft tumor, which can be reversed by miR-199a inhibitor. Conclusion Propofol can suppress PAK4 expression by inducing miR-199a up-regulation, thereby inhibiting the proliferative, invasive and migrating abilities of NSCLC.

A range of circular (Circ) RNAs have been demonstrated to be of therapeutic significance for the treatment of acute lymphoblastic leukemia (ALL). Here, we investigated the mechanisms underlying the action of Circ-PRKDC and the microRNA-653-5p/Reelin (miR-653-5p/RELN) axis in T-cell ALL (T-ALL).Clinical specimens were obtained from patients with T-ALL (n = 39) and healthy controls (n = 30). In each specimen, we determined the expression levels of Circ-PRKDC, miR-653-5p, and RELN. Human T-ALL cells (Jurkat) were transfected with Circ-PRKDC- or miR-653-5p-related sequences to investigate cell proliferation, apoptosis, and autophagy. We also determined the levels of Circ-PRKDC, miR-653-5p, RELN, and signaling proteins related to phosphoinositide 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). Finally, we decoded the interactions between Circ-PRKDC, miR-653-5p, and RELN. The expression levels of Circ-PRKDC and RELN were upregulated in T-ALL tissues and cells while the levels of miR-653-5p were downregulated. Thereafter, then silencing of Circ-PRKDC, or the enforced expression of miR-653-5p, repressed the expression of RELN and the activation of the PI3K/AKT/mTOR signaling pathway, thus enhancing cell autophagy and apoptosis, and disrupting cell proliferation. Circ-PRKDC acted a sponge for miR-653-5p while miR-653-5p targeted RELN. The knockdown of miR-653-5p abrogated the silencing of Circ-PRKDC-induced effects in T-ALL cells. The depletion of Circ-PRKDC elevated miR-653-5p to silence RELN-mediated PI3K/AKT/mTOR signaling activation, thereby enhancing autophagy and apoptosis in T-ALL cells.

This study aims to clarify the function of transient receptor potential melastatin 8 (TRPM8) in colon cancer liver metastasis. First, TRPM8 expression was determined by Western blotting in colon cancer patients with/without liver metastasis. Second, colon cancer cells were grouped into Mock, siCON, and siTRPM8 groups. Then, a series of in vitro experiments were conducted. Last, CT26 cells were used to construct colon cancer liver metastasis models on mice in vivo, followed by comparison of liver metastasis and determination of AKT/glycogen synthase kinase-3β (GSK-3β) pathway. Consequently, TRPM8 was upregulated in both colon cancer patients with/without liver metastasis, especially in those with metastasis. Compared with Mock and siCON groups, cells in siTRPM8 group demonstrated significant decreases in clone numbers, cell invasion, and migration; and obvious downregulations of p-AKT/AKT, p-GSK3β/GSK3β, Snail, and Vimentin, with an upregulation of E-cadherin. For in vivo experiments, a sharp decrease was observed in metastatic liver of mice in siTRPM8 group, with significant downregulations of p-AKT/AKT, p-GSK3β/GSK3β, Snail, and Vimentin and an upregulation of E-cadherin, as compared with Mock and siCON groups. Thus, TRPM8 was upregulated in colon cancer patients with liver metastasis, and silencing TRPM8 may suppress the progression and epithelial-mesenchymal transition of colon cancer cells to block its liver metastasis possibly by inhibiting AKT/GSK-3β pathway.

Chronic hepatitis B virus (HBV) infection can lead to fibrosis, liver cirrhosis, and primary hepatocellular carcinoma. Investigating host factors that regulate HBV replication helps to identify antiviral targets. In the current study, we identified Nicotinamide N-Methyltransferase gene (NNMT) as a novel factor that regulates HBV transcription. NNMT is up-regulated at both the mRNA and protein levels in HepG2.2.15 cells compared to HepG2 cells. Overexpression of NNMT reduces HBV replication in several cell models, while knockdown of NNMT enhances HBV DNA levels. Mechanistically, NNMT suppresses HBV DNA replication by inhibiting HBV RNA transcription. The region required for the inhibitory effect of NNMT was narrowed to nt 1672-1708 in enhancer II by luciferase assays. On the other hand, ChIP assays and EMSA results showed that NNMT does not bind to this region substantially, either directly or indirectly. Next, a collection of hepatic nuclear receptor transcription factors was screened to determine whether they were affected by NNMT overexpression. NR5A1, a positive regulator of HBV replication, decreased significantly after NNMT overexpression. Collectively, the findings of this study shed light on the regulation of HBV transcription.

One of the most desirable targets for HBV medications is the sodium taurocholate cotransporting polypeptide (NTCP), an entry receptor for the hepatitis B virus (HBV). N-myristoylated preS1 2-48 (Myrcludex B or Hepcludex), an NTCP-binding peptide from the large surface protein of HBV, has been developed as the first-in-class entry inhibitor. However, its relatively large molecular weight contributes to increased immunogenicity and antibody production. As a result, it is preferable to look for an NTCP-binding peptide with a smaller size. To do this, we developed a human cell surface display strategy and screened peptides based on preS1-21. PreS1-21 (genotype D) was extended by 7 random amino acids and fused with mCherry and FasL transmembrane domain. The pooled constructs were transfected into HEK293 cells by using the transposon/transposase system to create a library displaying various peptides on the cell surface with red fluorescence. On the other hand, we expressed NTCP protein fused with EGFP on HEK293 and used the membrane lysate containing NTCP-GFP as the bait protein to select peptides with increased NTCP affinity. After 7 cycles of selection, the deep sequencing results revealed that some polypeptides were more than 1,000 times enriched. Further screening of the mostly enriched 10 peptides yields the peptide preS1-21-pep3. Replacing the preS1-21 sequence of preS1-21-pep3 with those from different genotypes demonstrated that the consensus sequence of genotype A-F had the best performance. The peptide (Myr-preS1-21-pep3) was synthesized and tested on the HepG2-NTCP cell model. The results showed that Myr-preS1-21-pep3 is approximately 10 times more potent than the initial peptide Myr-preS1-21 in preventing HBV infection. In conclusion, we developed a new strategy for screening peptides binding to membrane proteins and identified a new NTCP-binding peptide with a much smaller size than Hepcludex.

We report a feasibility study of pure leptonic decay $D_s^+\to\mu^+\nu_\mu$ by using a fast simulation software package at STCF. With an expected luminosity of $1~\mathrm{ab}^{-1}$ collected at STCF at a center-of-mass energy of 4.009 GeV, the statistical sensitivity of the branching fraction is determined to be 0.3\%. Combining this result with the $c\rightarrow s$ quark mixing matrix element $|V_{cs}|$ determined from the current global Standard Model fit, the statistical sensitivity of $D_s^+$ decay constant, $f_{D_s^+}$, is estimated to be 0.2\%. Alternatively, combining the current results of $f_{D_s^+}$ calculated by lattice QCD, the statistical sensitivity of $|V_{cs}|$ is determined to be 0.2\%, which helps probe possible new physics beyond. The unprecedented precision to be achieved at STCF will provide a precise calibration of QCD and rigorous test of Standard Model., Comment: 8pages, 7 figures

Glioblastoma (GBM) is one of the most common malignant and incurable brain tumors. The identification of a gene signature for GBM may be helpful for its diagnosis, treatment, prediction of prognosis and even the development of treatments. In this study, we used the GSE108474 database to perform GSEA and machine learning analysis, and identified a 33-gene signature of GBM by examining astrocytoma or non-GBM glioma differential gene expression. The 33 identified signature genes included the overexpressed genes COL6A2, ABCC3, COL8A1, FAM20A, ADM, CTHRC1, PDPN, IBSP, MIR210HG, GPX8, MYL9 and PDLIM4, as well as the underexpressed genes CHST9, CSDC2, ENHO, FERMT1, IGFN1, LINC00836, MGAT4C, SHANK2 and VIPR2. Protein functional analysis by CELLO2GO implied that these signature genes might be involved in regulating various aspects of biological function, including anatomical structure development, cell proliferation and adhesion, signaling transduction and many of the genes were annotated in response to stress. Of these 33 signature genes, 23 have previously been reported to be functionally correlated with GBM; the roles of the remaining 10 genes in glioma development remain unknown. Our results were the first to reveal that GBM exhibited the overexpressed GPX8 gene and underexpressed signature genes including CHST9, CSDC2, ENHO, FERMT1, IGFN1, LINC00836, MGAT4C and SHANK2, which might play crucial roles in the tumorigenesis of different gliomas.

Motivation MIB2 (metal ion-binding) attempts to overcome the limitation of structure-based prediction approaches, with many proteins lacking a solved structure. MIB2 also offers more accurate prediction performance and more metal ion types. Results MIB2 utilizes both the (PS)2 method and the AlphaFold Protein Structure Database to acquire predicted structures to perform metal ion docking and predict binding residues. MIB2 offers marked improvements over MIB by collecting more MIB residue templates and using the metal ion type-specific scoring function. It offers a total of 18 types of metal ions for binding site predictions. Availability and implementation Freely available on the web at http://bioinfo.cmu.edu.tw/MIB2/. Supplementary information Supplementary data are available at Bioinformatics online.

As a short peptide containing active thiol group, glutathione (GSH) participates in many cellular reactions, so it is of great significance to detect cellular GSH. In this work, amino-rich graphene quantum dots (GQDs) were synthesized, which could coordinate with copper ions (Cu2+) and yield aggregation-induced fluorescence quenching. However, GSH owns stronger coordination ability with Cu2+, so that GSH could promote the dissociation of Cu2+ from the surface of GQDs, and then led to the fluorescence recovery of GQDs. In BR buffer medium at pH 6.8, GSH was able to gradually recover the fluorescence of GQDs (1 μg/mL) that was quenched by Cu2+ (250 μmol/L), which could be finished within 20 min. Additionally, the recovery degree of fluorescence was linear to the concentration of GSH in the range of 20–500 μmol/L with a detection limit of 3.4 μmol/L. This method was applicable to the detection of GSH in cell lysate by the switchable function of Cu2+ to improve the selectivity.

Ribonucleotides are usually functioned as biomarkers to diagnose diseases and monitor the life activities in living organisms, and their discrimination is of great significance but challenging. Taking advantage of the unique characteristics of gold nanorods (AuNRs), herein, a colorimetric sensor array for discrimination of twelve ribonucleotides was developed based on the chemical etching of AuNRs with controllable aspect ratios. During the etching process, AuNRs were preferentially shortened and eventually turned into Au(III) state by Fenton’s reaction. The morphological change of AuNRs led to the significant color change and blue shift in the corresponding extinction spectrum. However, when Fe2+ bound with ribonucleotides, the Fenton’s reaction was prevented and the ability to etch AuNRs was weakened or disappeared. Due to the different structures of nucleotides, the binding ability of them with Fe2+ was distinct, resulting in the discrepancy in the chemical etching of AuNRs, which could be developed for distinguishing ribonucleotides. Moreover, the proposed sensor array was successfully explored to distinguish ribonucleotides in complex human urine samples.

MicroRNAs, as one kind of significant biomarkers, play indispensable roles in the diagnosis and treatment of cancers. Yet, owing to low expression and high sequence homology, high sensitivity and specificity for microRNA detection are greatly challenging. Herein, a sensitive sensing platform with high specificity was developed for microRNA-27a (miRNA-27a) based on the miRNA-27a-triggered chemical etching of gold nanorods to a smaller size, which was accompanied by a significant blue shift and a large decrease of intensity in the localized surface plasmon resonance (LSPR) scattering and remarkable color variability from red to green. When combined with strand displacement reactions as well as liposome signal amplification and transduction, the proposed bioassay presented high selectivity toward miRNA-27a in a dynamic range from 100 fM to 3 pM and a low limit of detection of 16.5 fM (3σ/

Photothermal effects (PTEs) have been greatly concerned with the fast development of new photothermal nanomaterials. Herein we propose a photothermal immunoassay (PTIA) by taking mycotoxins (AFB1) as an example based on the PTEs of plasmonic Cu2–xSe nanocrystals (NCs). By loading plasmonic Cu2–xSe NCs into liposomes to form photothermal soft nanoballs (ptSNBs), on which aptamer of AFB1 previously assembled, a sandwich structure of AFB1 could be formed with the aptamer on ptSNBs and capture antibody. The heat released from the ptSNBs under NIR irradiation, owing to the plasmonic photothermal light-to-heat conversion through photon–electron–phonon coupling, makes the temperature of substrate solution increased, and the increased temperature has a linear relationship with the AFB1 content. Owing to the large amounts of plasmonic Cu2–xSe NCs in the ptSNBs, the PTEs get amplified, making AFB1 higher than 1 ng/mL detectable in food even if with a rough homemade immunothermometer. The proposal of PTIA opens a ne...

A range of circular (Circ) RNAs have been demonstrated to be of therapeutic significance for the treatment of acute lymphoblastic leukemia (ALL). Here, we investigated the mechanisms underlying the action of Circ-PRKDC and the microRNA-653-5p/Reelin (miR-653-5p/RELN) axis in T-cell ALL (T-ALL).Clinical specimens were obtained from patients with T-ALL (n = 39) and healthy controls (n = 30). In each specimen, we determined the expression levels of Circ-PRKDC, miR-653-5p, and RELN. Human T-ALL cells (Jurkat) were transfected with Circ-PRKDC- or miR-653-5p-related sequences to investigate cell proliferation, apoptosis, and autophagy. We also determined the levels of Circ-PRKDC, miR-653-5p, RELN, and signaling proteins related to phosphoinositide 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). Finally, we decoded the interactions between Circ-PRKDC, miR-653-5p, and RELN. The expression levels of Circ-PRKDC and RELN were upregulated in T-ALL tissues and cells while the levels of miR-653-5p were downregulated. Thereafter, then silencing of Circ-PRKDC, or the enforced expression of miR-653-5p, repressed the expression of RELN and the activation of the PI3K/AKT/mTOR signaling pathway, thus enhancing cell autophagy and apoptosis, and disrupting cell proliferation. Circ-PRKDC acted a sponge for miR-653-5p while miR-653-5p targeted RELN. The knockdown of miR-653-5p abrogated the silencing of Circ-PRKDC-induced effects in T-ALL cells. The depletion of Circ-PRKDC elevated miR-653-5p to silence RELN-mediated PI3K/AKT/mTOR signaling activation, thereby enhancing autophagy and apoptosis in T-ALL cells.

As an important biomarker for early diagnosis of cancers, sensitive detection and high-resolution imaging of microRNA-21 in cancer cells have become important and challengeable. In this work, highly sensitive detection and spatial imaging of intracellular microRNA-21 were realized by the reduced signal background through vertical polarization excitation with a polarizer. The lateral local surface plasmon resonance property of gold nanorods (AuNRs) displayed a pronounced green color with low scattering intensity, which was adjusted to red color with strong scattering intensity when the core-satellite gold nanoparticle (AuNP) assembly was constructed on the side of AuNRs through a catalyzed hairpin assembly (CHA) circuit in the presence of microRNA-21. This unique approach allows for effectively reducing the strong background signal to improve the sensitivity of detection. Additionally, the proposed strategy can not only realize the sensitive detection of microRNA-21 with the limit of detection as low as 2 pM (3σ) but also achieve the high spatial imaging of cancer cells, which provided a specific strategy for the construction and imaging of intracellular imaging probes. It is believed that the simple and sensitive approach on the basis of lateral local surface plasmon resonance property of anisotropic AuNRs with excellent sensitivity combined with high spatial imaging holds promising potentials to visualize intracellular microRNAs with low abundance.

Single amino acid variation (SAV) is an amino acid substitution of the protein sequence and might influence the whole protein structure, binding affinity, or functional domain and related to disease, even cancer. However, to clarify the relationship between SAV and cancer using traditional experiments is time and resource consuming. Though there are some SAVs predicted methods using the computational approach, most of them predict the protein stability changed caused by SAV. In this work, all of the SAV characteristics generated from protein sequences, structures, and micro-environment would be converted into feature vectors and fed into an integrated predicting system by using Support Vector Machine and genetic algorithm. The critical features were used to estimate the relationship between their properties and cancer caused by SAVs. In the results, we have developed a prediction system based on protein sequence and structure, which could distinguish the SAV is related to cancer or not, and the accuracy, the Matthews correlation coefficient, and the F1-score yield to 90.88%, 0.77 and 0.83, respectively. Moreover, an online prediction server called CanSavPre was built (http://bioinfo.cmu.edu.tw/CanSavPre/), which will be a useful, practical tool for cancer research and precision medicine.

As a mucopolysaccharide sulfate anticoagulant drug, heparin plays important roles in clinic. In this work, heparin was analyzed based on the nanometal surface energy transfer (NSET) between gold nanorods (AuNRs) and tetrakis (4-sulfophenyl) porphyrin (TPPS4) fluorescent molecules. The results showed that AuNRs could bind TPPS4 by electrostatic interaction and coordination to quench its fluorescence. While heparin was able to bind AuNRs with a stronger electrostatic interaction to compel TPPS4 to leave AuNRs surface, leading to the fluorescence recovery of TPPS4, which was proportional to the concentration of heparin in a range of 0.05∼2 μg/mL with the detection limit as low as 6.7 ng/mL (3σ). Based on this, a NSET platform for the analysis of trace heparin sodium was proposed with fast response, high sensitivity and excellent specificity, which was successfully applied to the detection of heparin in injection with the satisfactory result. Importantly, the NSET mechanism was fully discussed.

As an important biomarker of malignant tumors, spermine is closely related with some diseases. In this work, a nanometal surface energy transfer (NSET) strategy via the positively charged gold nanorods (AuNRs) and the negatively charged tetrakis (4-sulfonatophenyl) porphyrin (TPPS4) was developed to detect spermine in human urine. Under acidic condition, spermine possessed multi-cationic property and a strong affinity towards the anionic phosphate backbone of calf thymus DNA (ctDNA) by electrostatic attraction as well as the groove binding, which enabled to regulate the process of NSET between AuNRs and TPPS4, leading to the fluorescence quenching of TPPS4. Moreover, the quenched fluorescence was proportional to the concentration of spermine, which was applicable to monitor the level of spermine in human urine in the concentration range of 0.5–7.5 μM. The NSET platform for spemine is simple, selective and time-saving, which has great significance in early cancer diagnosis.

As an antibiotic, tetracycline has been widely used against bacterial infection or as feed additives for growth promotion, which may lead to the enrichment of antibiotic residues in animals or their products. Therefore, the detection of tetracycline is closely related to human health. The morphological transformation of CoOOH nanoflakes induced by tetracycline was monitored by scanning electron microscope images, dark-field light scattering images and optical spectra, which found that tetracycline could decompose CoOOH nanoflakes into small nanoparticles with low light scattering signal. As a result, the reduced light scattering of CoOOH nanoflakes was proportional to the increased concentration of tetracycline in the range of 1.0–250 μmol/L, and the limit of determination (LOD) was 0.23 μmol/L (3σ/k). Most foreign substances did not interfere in the analysis of tetracycline. Furthermore, the concentration of tetracycline in different milk samples detected with the standard addition method was so low that it accorded with the safety regulation, which was similar to the detection result with high-performance liquid chromatography (HPLC).

As the main final products of the purine metabolism in human body, uric acid (UA) usually presents in serum and urine. Thus, the level of UA in biology is closely related to human health. In this work, the ultra-small CuS nanoparticles (NPs) were demonstrated to possess intrinsic peroxidase-like activity towards 3,3',5,5'-tetramethylbenzidine (TMB) substrate in the presence of H2O2, which yielded the blue oxidized TMB (oxTMB) with strong absorption at 653 nm. Furthermore, H2O2 could be produced by the enzymatic reaction between UA and uricase to yield the blue oxTMB with the peroxidase mimetics activity of CuS NPs, which provided a sensitive and colorimetric method for UA detection with a linear range from 1.0 × 10−6 M to 1.0 × 10−4 M and a detection limit of 1.0 × 10−7 M. Moreover, the proposed method was successfully applied to the determination of UA in human serum samples, which supplied a similar result to the clinical method.

As a major metabolic product of purine nucleotides, uric acid (UA) usually presents in urine and serum, which is closely related to human health. With the catalysis by uricase, uric acid can yield allantoin, CO2 and H2O2. Then, the produced H2O2 is able to decompose CoOOH nanoflakes into Co2+, resulting in a smaller size with weakened light scattering. This work provides a simple and selective light scattering method for UA analysis with a linear range from 1.0 × 10−5 to 1.0 × 10−3 M and a detection limit of 1.0 × 10−6 M. In addition, this method has been successfully applied to the determination of UA in human serum samples with similar results to clinical methods.

Ricin is an extremely potent ribosome-inactivating protein and serves as a likely food biocontaminant or biological weapon. Thus, simple, sensitive and accurate analytical assays capable of detecting ricin are urgently needed to be established. Herein, we present a novel method for ricin B-chain (RTB) detection by using two materials: (a) a highly efficient hybrid probe that was formed by linking a glucose oxidase (GOD)-encapsulated liposome (GOD-L) to magnetic beads (MBs) through hybridization between an aptamer and a blocker and (b) a new low-background g-C3N4-MnO2 sandwich nanocomposite that exhibits fluorescence resonance energy transfer (FRET) between the g-C3N4 nanosheet and MnO2. In the presence of RTB, the strong binding between RTB and the aptamer can release the blocker-linked liposome from the surface of the MBs. After magnetic separation, the decomposed liposome can release GOD to catalyze the oxidation of glucose, generating a certain amount of H2O2. Then, H2O2 can reduce MnO2 of the g-C3N4-MnO2 nanocomposite to Mn2+, which leads to the elimination of FRET. Thus, the fluorescence of the g-C3N4 nanosheet will be turned on. Because of the excellent signal amplification ability of liposome and the characteristic highly sensitive response of the g-C3N4-MnO2 nanocomposite toward H2O2, RTB could be detected sensitively based on the significantly enhanced fluorescent intensity. The linear range of detection was from 0.25 μg mL-1 to 50 μg mL-1 and the limit of detection (LOD) was 190 ng mL-1. Moreover, the proposed assay was successfully applied in the detection of the entire ricin toxin content in a castor seed.

Plasmonic gold nanorods are promising and sensitive light scattering probes, which can reach the single particle level. Herein, we present the scattering properties of gold nanorods for time-resolved visual detection of heparin based on the rapid etching of gold nanorods under dark-field microscopy.

Owing to the sharp edge-enhanced electric field, gold triangular nanoplates (AuNPLs) exhibit strong localized surface plasmon resonance (LSPR) scattering and display as red spots with high intensity and narrow distribution under dark-field microscopy (DFM), based on which sensitive sensing applications could be developed. As a concept of proof, the inhibition effects of pyrophosphate (PPi) against the etching of AuNPLs based on Cu

Background Increasing evidence have demonstrated that serum extracellular vesicle microRNAs (EV-miRNAs) are promising noninvasive biomarkers for various cancer types. Objective In this study, we aimed to investigate and evaluate the potential clinical significance of serum EV-miR-10b for acute myeloid leukemia (AML). Methods Blood samples were collected from a cohort of 95 de novo AML patients and 80 healthy individuals. Of all AML patients, 51 patients were considered as cytogenetic normal AML (CN-AML). Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to measure the expression levels of serum EV-miR-10b. Results The extracellular vesicles we extracted from the serum samples were positive for EV/exosome markers including TSG101, CD63, Flotillin-1 and CD9. The expression levels of serum EV-miR-10b were significantly higher in AML/CN-AML patients than healthy controls. In addition, serum EV-miR-10b expression was strongly correlated with aggressive clinical characteristics. Moreover, receiver operating characteristic analysis showed serum EV-miR-10b yielded an area under the curve of 0.875, with 77.89% specificity and 82.50% sensitivity in identifying AML patients from normal controls. Furthermore, AML patients with higher serum EV-miR-10b expression had significantly shorter survival and serum EV-miR-10b was demonstrated to be an independent prognostic marker for overall survival in AML. Conclusions Taken together, serum EV-miR-10b might serve as a promising biomarker for predicting the prognosis of AML.

Biothiols play important roles in regulating redox balance in biological systems, but their discrimination is challengeable. In this work, a colorimetric nanosensing array for biothiols was established, which was composed of gold nanorods (AuNRs) and metal ions (Hg2+, Pb2+, Cu2+, Ag+). By employing label-free AuNRs as the colorimetric probe, and the color and spectral changes of AuNRs as the output signal, principal component analysis (PCA) was applied to processing the signal and generating a clustering map. Due to the different binding affinity between biothiols and metal ions, AuNRs exhibited a unique pattern to form a fingerprint-like colorimetric array, which was able to discriminate five biothiols by the naked eyes. This strategy combines PCA and sensor array to achieve rapid and accurate discrimination and detection of biothiols. In addition, the method shows the great potential in analysis of biothiols in human urine samples.

Photothermal effects (PTEs) have been greatly concerned with the fast development of new photothermal nanomaterials. Herein we propose a photothermal immunoassay (PTIA) by taking mycotoxins (AFB

The rapid and sensitive assay is the goal for advancing analytical methods and techniques to save time and achieve the early diagnosis, which are of crucial importance in clinic. The concept of synergistic effects for fastening reaction and improving sensitivity was constructed by introducing iodide (I-) to the typical Fenton's reaction system as a model reaction, which was calculated theoretically and demonstrated experimentally. In an acid medium, the simultaneous presence of Fe2+ and I- could significantly improve the oxidation capability and rate of H2O2 to etch gold nanorods (AuNRs) because of the synergistic effect, which was further successfully applied to the rapid and sensitive assay of cholesterol, glucose and uric acid in human serum. In this work, the synergistic effect greatly improved the reaction rate and sensitivity, which showed potential applications in biological sensing and clinic diagnosis.

Ricin is an extremely potent ribosome-inactivating protein and serves as a likely food biocontaminant or biological weapon. Thus, simple, sensitive and accurate analytical assays capable of detecting ricin are urgently needed to be established. Herein, we present a novel method for ricin B-chain (RTB) detection by using two materials: (a) a highly efficient hybrid probe that was formed by linking a glucose oxidase (GOD)-encapsulated liposome (GOD-L) to magnetic beads (MBs) through hybridization between an aptamer and a blocker and (b) a new low-background g-C3N4-MnO2 sandwich nanocomposite that exhibits fluorescence resonance energy transfer (FRET) between the g-C3N4 nanosheet and MnO2. In the presence of RTB, the strong binding between RTB and the aptamer can release the blocker-linked liposome from the surface of the MBs. After magnetic separation, the decomposed liposome can release GOD to catalyze the oxidation of glucose, generating a certain amount of H2O2. Then, H2O2 can reduce MnO2 of the g-C3N4-MnO2 nanocomposite to Mn2+, which leads to the elimination of FRET. Thus, the fluorescence of the g-C3N4 nanosheet will be turned on. Because of the excellent signal amplification ability of liposome and the characteristic highly sensitive response of the g-C3N4-MnO2 nanocomposite toward H2O2, RTB could be detected sensitively based on the significantly enhanced fluorescent intensity. The linear range of detection was from 0.25 μg mL-1 to 50 μg mL-1 and the limit of detection (LOD) was 190 ng mL-1. Moreover, the proposed assay was successfully applied in the detection of the entire ricin toxin content in a castor seed.

In this paper, a CTS (continuous transverse stub) antenna array using SIW (substrate integrated waveguide) technology is proposed. The antenna consists of quasi-TEM wave generator, E-plane corporate feeding network and radiation slots. The pillbox structure is used to generate quasi-TEM wave in the oversized rectangular waveguide. Then the energy is divided by E-plane corporate feeding network and fed the radiation slots. From the simulated results, it can be seen that the reflection coefficient is below -10 dB from 22GHz to 28GHz, and gain is about 24.3dBi at 25GHz with the efficiency of 59%.

The Jinlongshan gold deposit, Shaanxi Province, is a large Carlin-type deposit in the Western Qinling Gold Province (WQGP) in the Qinling Orogenic Belt, Central China. In this study, we present new EPMA and LA–ICP–MS geochemical data on the Fe–S–As minerals at Jinlongshan, which consist mainly of pyrite, arsenian pyrite and arsenopyrite. Diagenetic pyrite (Py0) is preferentially hosted in the sedimentary rocks as rounded or framboidal aggregates. Three types of hydrothermal pyrite (Py1, Py2 and Py3) and two types of arsenopyrite (Apy1 and Apy2) were newly identified in the ores and wall-rocks: fine-grained Py1 and Apy1 were formed at the early mineralization stage; coarse-grained Py2 and Apy2 were formed at the middle mineralization stage; and Py3 with stibnite were formed at the late mineralization stage. Their trace elements differ in concentrations, associations and rim–core zonations, implying different genesis and crystallization processes. Py0 is As-poor (Au

The Jinchang gold deposit is located in the easternmost portion of the Central Asian Orogenic Belt (CAOB), and represents one of the major gold districts in eastern Jilin–Heilongjiang provinces of China. The gold ore bodies are hosted mainly in altered Mesozoic granitoids, breccia pipes and ring and radial faults. Gold mineralization consists of alteration (stockwork in hydrothermally altered granites), breccia, and quartz-sulfide vein-types. Alteration assemblages around the alteration-style ore body show a vertical sequence of potassic, phyllic, and propylitic zones. In this study, we present U–Pb and Lu–Hf isotope data on zircons derived from mineralized granophyric granite, biotite monzogranite, granodiorite, and granite porphyry, and sericite Rb–Sr ages from the Jinchang gold deposit. The results show 206Pb/238U ages of 201 ± 3 Ma (MSWD = 1.1), 203 ± 4 Ma (MSWD = 1.4), 201 ± 5 Ma (MSWD = 2.1), and 110 ± 3 Ma (MSWD = 1.6), respectively. Sericite from the gold-mineralized phyllic-altered granodiorite and granite porphyry returns Rb–Sr isochron ages of 110 ± 4 Ma (MSWD = 1.04) and 107 ± 5 Ma (MSWD = 0.91), respectively. Our new data indicate that the gold mineralization at Jinchang took place at ca. 110 Ma and was temporally related to intrusion of the granite porphyry. Zircon e Hf (200 Ma) values of the ca. 200 Ma granites vary from − 4.8 to + 8.1, with TCDM model ages of 727–1535 Ma, reflecting their derivation mainly by partial melting of juvenile Proterozoic crust. The gold-bearing 110 Ma granite porphyry returns e Hf (110 Ma) values in the range of − 1.6 to + 9.8, with TCDM model ages of 542–1069 Ma, suggesting partial melts of juvenile Proterozoic crust with notable input of mantle components as compared to the ca. 200 Ma granites. Compiled oxygen (δ18OSMOW = − 0.7–10.1) and hydrogen (δDSMOW = − 99 to − 70) stable isotopic values of quartz from ores indicate that the ore-forming fluids were predominantly exsolved from magmas with minor amount of meteoric water in quartz-sulfide veins at the late stage. The Hf isotope data from the granite porphyry, integrated with the results from previous data on S and Pb isotopic composition of ores, constrain the source of ore-forming components as lower crust with discernible mantle inputs and wall rock assimilation. Our results have implications bearing on the widespread magmatism and metallogenic event during the Early Cretaceous time in East China, and link them to mantle upwelling that contributed both heat and volatiles for crustal melting and scavenging of metals which in turn were concentrated in upper crustal levels through exsolution for the magmas.

This paper calculate the transmission loss caused by generation right trade and its impact on system based on the DC power flow equation. This method takes into account each power flow state and more accord with the practical situation of generation right trade. By analyzing the mechanism and process of generation right trade, to the unreasonable method that averagely allocate the trading power in trading hours under the daily generation right trade mode, this paper propose a method to fit a trading power allocation curve based on cubic spline interpolation and power system. The curve can be adjusted by trading power and replace the traditional averagely allocate method. Combined with three kinds of allocating situation, the rationality of this paper has been tested on IEEE-13 bus system.

Based on being a modeling process of the network learning system essentially, it has three elements of learning environment, learning, learning activities, and three dimensions of conceptual model, physical model and logical model. From the method aspect, it has analytical method, theoretical basis, model design; from logical view, it has branch learning resource, learning control management and students' interaction layer. Focus on the analysis of the learning system model of learning resources and learning system modeling.

[Purpose] It is the Network environment model that is used in this paper，in order to explore the impact of cooperative learning, cooperative learning network platform and build the main model. [Method] Through system analysis, development and design of functions, environmental test solution platform for building collaborative learning network etc., introduce experimental control network measures to explore the main modes of cooperative learning. [Results] The results show that: as the most popular online communication media, E-mail eventually becomes a natural cross-class, inter-school and inter-regional cooperation as well as transnational study of selection. To build a network of cooperative learning platform should adhere to the technical point of view, The main mode of the network cooperative learning is based on a team or task-based learning network cooperative learning.[Conclusions] Network cooperative learning can make different levels of learners in the process of completing tasks, with the network environment, breaking through the restrictions of classroom learning environment, to exchange, to communicate, to cooperate and to promote comprehensive development of the learner.

[Purpose] The paper aims to explore instructional design of the structure under the web-based environment, as well as the similarities and differences with the traditional instructional design; with its teaching resources，methods and students' ability to develop design strategies. [Method]Through the introduction of systems analysis and experimental control and from the network hardware environment, resources, environment and cultural environment the network learning environment design is brought forth. [Results]The results show that the network environment, information technology, instructional design, which are based on the learner and the teaching process for the study, aims to achieve a good learning environment, to organize the various elements; to form an ordered system; particularly to emphasis on learning characteristics and learning needs analysis of the measurement, to focus on the design of learning environments and “communication-oriented” classroom activities. [Conclusions] This instructional design under network information technology environment is a very important significance for a variety effective learning activities, for students to stimulate motivation to learn.

[Purpose] This paper is to explore network information environment composition and characteristics of multimedia teaching and research, teaching model and their building. [Method] Literature, experimental research, questionnaires, interviews, training and other research methods are used. [Results] Multimedia teaching by teachers, sharing with learners, its content, its transmission environment, and other basic elements of composition, characteristics reflected on the teaching philosophy of updates, its extension of the concept and functions of the teacher-role changes, as the changing role of teachers and the capacity requirements, learner’s autonomy and self-control ability to enhance the teaching resources and their sharing of rich, personalized teaching process, diversity of teaching content, modernization of teaching methods and so on are achieved. [Conclusions] The teaching concept of network information environment is a multi-media teaching method and educational philosophy with a series of changes and transference. It is a neo-strategy to adapt the information society, knowledge economy, market competition, high-tech, digital environment with their application type, complex and creative training mode of education as well.

The basic linear data structure of linear table data -- analysis of the physical structure of the two kinds of method: the linear order of the table to achieve and chain to achieve. The storage structure of insert operation, delete operation, lookup operation to study computer solutions. Compares and analyzes linear data structure of the physical implementation of the advantages and disadvantages.

In order to solve the problem of chain wearing elongation due to random assembly of roller chain sleeve crevice orientation, a novel roller chain sleeve crevice identification and orientation device is proposed. By means of force analysis of the identified sleeve, establish the shape and material parameter relation of drive driven sprocket and collet, to fulfill high-efficiency and high-accuracy roller chain assembly. The tested chain sleeve is 10B-1, two hundred sleeve crevice identification and orientation were tested 50 times. Every test average time is 182.3s and all the sleeve crevice out of the discharge opening is collinear. The rationality and practical applicability of roller chain sleeve crevice identification and orientation device design procedure is verified.

In order to apply silent chain on conveyor, double-pitch time-sharing meshing silent chain is proposed, and by comparing with traditional silent chain with same pitch, the self-weight 20%~30% of this chain is reduced. According to meshing theory, parameters are designed for double-pitch time-sharing meshing silent chain to make each tooth profile of chain plate involving in meshing and time-sharing load bearing and to change the meshing state of traditional silent chain in the meshing process. Noise comparison test is conducted to verify its excellent performance, when rotate speed is 350r/min, the noise of double-pitch time-sharing mesh silent chain is 4.6dB lower than traditional double-pitch roller chain. Meanwhile, 250h abrasion test is conducted, the abrasion elongation of chain is 0.23% after test, which is significantly lower than traditional double-pitch roller transport chain. The rationality of new chain design is proved by test result, which provides theoretical basis for applying silent chain on conveyor.

This paper proposes a graphical modeling method for inter-enterprise service interactions during outsourcing production processes. The relevant concepts of service interaction are firstly defined. The proposed method borrows from the principle of graphical schema modeling to depict the service interaction processes and the overall flow during inter-enterprise outsourcing production. Graphical units are illustrated, and the connections of these units are formalized. Based on that, the overall interaction event flow is formed. An exemplary case is studied to verify the proposed method and some improvements are discussed further. It is expected that our methods will provide instructions for inter-enterprise service interaction analysis and value co-creation when dealing with outsourcing production orders.

In order to solve the problem of blurry sight made by rain drop on the rearview mirror on rainy day, a rain-removing device making use of piezoelectric vibrator is put forward. Design the structure of the rain-removing device, build its finite element model and modal analysis for the piezoelectric vibrator is done. Piezoelectric rain-removing device prototype is manufactured and amplitude of the mirror is tested with different voltages and frequency. At last rain-removing effect for the rear mirror is measured with varies of angle at which piezoelectric vibrator is installed. The proportion of the removed rain drop is 80% when piezoelectric vibrator angle is 60° and the voltage and frequency on the piezoelectric vibrator is100V and 800Hz respectively.

The principle of modified gear was applied to silent chain transmission, and tooth profile equation of the involute sprocket was derived, then method of processing gear using imaginary rack cutter solved modification coefficient of involute sprocket. When Center distance of silent chain drive changed smaller, processing method of sprocket modification coefficient and range of modification coefficient values were analysed. The method by changing the modification coefficient of involute sprocket solves the problem that the chain links are increased or decreased in the actual application to be unable to meet the requirements of specific center distance, thus improve transmission performance of silent chain.

In order to mitigate the impact and the polygon effect of the chain and the sprocket during the meshing process and achieve the purpose of noise reduction, a Hlow noiseH nanostructured metal mesh-polyurethane composite material split roller chain was designed by means of changing structure and material of chain roller. Noise testing and frequency spectrum analysis were conducted, for the new roller chain and the other three kinds of the same specification chains with different structural rollers, on the closed force flow noise test bench researched and developed independently. The results show that the new roller chain can absorb some of the impact energy, and reduce vibration and noise of chain drive. The noise level generated by the new roller chain is significantly lower than the other tested roller chains, especially in high frequency and high speed. The difference in noise level is actually 3-11dB in driving sprocket speed of 1000r/min, and a significant noise reduction is achieved. The results also verify low noise characteristics of the new roller chain and rationality of design method.

[Objective] study the self-innovative learning theory origin and new connotation under the network environment, research on how network environment provides technical support for independent innovation learning. [Process and methods] Adopting the combining of empirical analysis with normative analysis, system analysis with statistical analysis and actual investigation with literature research examine from hardware, resources and culture, technology and other means. [Results] No matter Bruner's cognition discovery theory, Su Baer's cognition assimilation theory or Rodgers's Humanism learning theory on learning view , has attached great importance to significance of learning autonomy in learning activities with the basic thought of learning the essential understanding and learning strategy; independent innovation learning expectations and the participation of the two basic characteristics; network environment provides a good technical support for the self innovative learning either from the cyber source volume, or interactive way, resource configuration and its retrieval and search reliability provided by the network technology. [Conclusion] The applications of Internet, multimedia technology, provide a very broad choice and reliable technical support for learners in the new environment to achieve a variety of means, way, time, space and virtual or real situation and to interact with information transmission web based learning exchanges, so that the innovative learning activities can be richer and more effective under the network environment.