Rapid Analysis of Seven Polyamines in Nephotettix cincticeps by Using Ultra-Performance Liquid Chromatography-Triple Quadrupole Mass Spectrometry.

A fast, simple, and sensitive method for the simultaneous determination of seven polyamines in Nephotettix cincticeps was developed based on ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-3Q-MS) together with liquid phase extraction. Polyamines in insect samples were extracted with HClO4 solution and then were separated and detected by UPLC-3Q-MS, which was equipped with a hydrophilic interaction liquid chromatography column, within 5 min without any derivatization procedure. The method has been successfully used to detect 7 polyamines in healthy and difluormethylornithine-treated adults of Nephotettix cincticeps with a method limit of detection and the method limit of quantitation of 24-139 pg/mg and 82-464 pg/mg, respectively, an intraday and interday relative standard deviation (RSD, n = 5) of 1.97-6.00% and 2.08-5.92% respectively, and a recovery of 86-115%. The success of this study provided a reliable method for the rapid and high-throughput detection of polyamines in the insect sample.

Screening of Cross-Reactive Aptamers for the Detection of 24 Quinolones by Using a Liebig's Law-Guided Parallel-Series Strategy.

Quinolones, a widely used class of antibiotics, present significant environmental and health concerns if they excessively remain in the environment and in food. Aptamers specific to quinolones can be applied as bioreceptors for the detection of quinolone residues in the environment and food. The quinolone family contains dozens of different individuals that share the same core structure coupled with various substituents at six different positions. The diversity and complexity of the substitution sites make it a challenge to choose a set of representative molecules that encompass all the desired sites and preserve the core molecular framework for the screening of quinolone-specific aptamers via systematic evolution of ligands by exponential enrichment (SELEX). To address this challenge, we introduce a novel parallel-series strategy guided by Liebig's law for isolating quinolone-specific cross-reactive aptamers by using the library-immobilized SELEX method. Through this approach, we successfully identified 5 aptamers (Apt.AQ01-Apt.AQ05) with high binding affinity and excellent specificity to 24 different quinolone individuals. Among them, Apt.AQ03 showcased optimal performance with affinities ranging from 0.14 to 1.07 µM across the comprehensive set of 24 quinolones, exhibiting excellent specificity against nontarget interferents. The binding performance of Apt.AQ03 was further characterized with microscale thermophoresis, circular dichroism spectra, and an exonuclease digestion assay. By using Apt.AQ03 as a bioreceptor, a fluorescence resonance energy transfer (FRET) aptasensor was developed for the detection of 24 quinolones in milk, achieving a remarkable detection limit of 14.5-21.8 ng/mL. This work not only establishes a robust and effective strategy for selecting cross-reactive aptamers applicable to other small-molecule families but also provides high-quality aptamers for developing various high-throughput and reliable methods for the detection of multiple quinolone residues in food.

Regulating the Growth Rate of Gold Nanobipyramids via a HCl-NADH-Ascorbic Acid System toward a Dual-Channel Multicolor Colorimetric Immunoassay for Simultaneously Screening and Detecting Multiple Sulfonamides.

It is an urgent need to develop simple and high-throughput methods for simultaneously screening and detecting multiple or groups of sulfonamides (SAs) in animal-derived foods since various SAs were alternately used in animal husbandry to avoid generating drug resistance. We herein developed a novel HCl-reduced nicotinamide adenine dinucleotide I (NADH)-ascorbic acid (AA)-mediated gold nanobipyramids (AuNBPs) growth system, which can precisely regulate the growth rate of AuNBPs, to generate two colorful and stable AA-corresponding multicolor signal channels with different sensitivities. Based on the HCl-NADH-AA-mediated AuNBP growth system, we further developed a dual-channel multicolor immunoassay for simultaneously realizing rapid screening and detection of 5 SAs (sulfamethazine, sulfamethoxydiazine, sulfisomidine, sulfamerazine, and sulfamonomethoxine) by using a paper-based analytical device for sensitively and stably reading out the signal and a broad-specificity anti-SAs antibody as a bio-receptor. The developed immunoassay has more color changes, a wider linear range, excellent specificity and stability, and two multicolor signal channels (L-channel and H-channel) with different sensitivities. The H-channel exhibited 7-8 SAs-corresponding color changes and can be used to detect 5 target SAs with a visual detection limit of 0.1-0.5 ng/mL and a spectrometry detection limit of 0.05-0.16 ng/mL. The L-channel exhibited 7-9 SAs-corresponding color changes and can be used to detect 5 target SAs with a visual detection limit of 2.0-6.0 ng/mL and a spectrometry detection limit of 0.40-1.47 ng/mL. The developed immunoassay was successfully used to simultaneously screen and detect low-concentration and high-concentration of target SAs in milk and fish muscle samples with a recovery of 85-110% and an RSD (n = 5) < 8%. The visual detection limit of our immunoassay is much lower than the maximum residue limit of total SAs in edible tissue. All above features make our immunoassay a promising assay for simultaneously realizing the rapid screening and quantitative determination of multiple SA residues in food by bare eye observation. It must be mentioned that our immunoassay may be expended as a general method for the simultaneous visual screening and detection of other drugs using the corresponding antibody as a recognition probe.

Genome-wide identification and expression analysis of the HVA22 gene family in cotton and functional analysis of GhHVA22E1D in drought and salt tolerance.

The HVA22 family of genes, induced by abscisic acid and stress, encodes a class of stress response proteins with a conserved TB2/DP1/HVA22 domain that are unique among eukaryotes. Previous studies have shown that HVA22s play an important role in plant responses to abiotic stresses. In the present study, 34, 32, 16, and 17 HVA22s were identified in G. barbadense, G. hirsutum, G. arboreum, and G. raimondii, respectively. These HVA22 genes were classified into nine subgroups, randomly distributed on the chromosomes. Synteny analysis showed that the amplification of the HVA22s were mainly due to segmental duplication or whole genome replication (WGD). Most HVA22s promoter sequences contain a large number of drought response elements (MYB), defense and stress response elements (TC-rich repeats), and hormone response elements (ABRE, ERE, SARE, etc.), suggesting that HVA22s may respond to adversity stresses. Expression profiling demonstrated that most GhHVA22s showed a constitutive expression pattern in G. hirsutum and could respond to abiotic stresses such as salt, drought, and low temperature. Overexpression of GhHVA22E1D (GH_D07G0564) in Arabidopsis thaliana enhances salt and drought tolerance in Arabidopsis. Virus-induced gene silencing of GhHVA22E1D reduced salt and drought tolerance in cotton. This indicates that GhHVA22E1D plays an active role in the plant response to salt stress and drought stress. GhHVA22E1D may act in plant response to adversity by altering the antioxidant capacity of plants. This study provides valuable information for the functional genomic study of the HVA22 gene family in cotton. It also provides a reference for further elucidation of the functional studies of HVA22 in plant resistance to abiotic stress response.

Is hepatic resection always a better choice than radiofrequency ablation for solitary hepatocellular carcinoma regardless of age and tumor size?

In this study, we aimed to compare survival outcomes after receiving radiofrequency ablation (RFA) and hepatic resection (HR) for solitary hepatocellular carcinoma (HCC) with stratification by tumor size and age. A retrospective cohort was obtained from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Patients were grouped by tumor size (0-2, 2-5, and > 5 cm) and age (>65 and ≤65). Overall survival (OS) and disease-specific survival (DSS) were assessed. For patients >65 with tumors measuring 0-2 and 2-5 cm, the HR group had better OS and DSS compared with the RFA group. For patients >65 with tumors > 5 cm, OS and DSS did not differ significantly between the RFA and HR groups (p = 0.262 and p = 0.129, respectively). For patients ≤65, the HR group had better OS and DSS compared with the RFA group regardless of tumor size. For patients with resectable solitary HCC, regardless of age, HR is the better choice not only for tumors ≤ 2 cm, but also for tumors 2-5 cm. For resectable solitary HCC with tumors ＞5 cm, HR is the better choice for patients ≤65 but for patients >65, the issue of treatment choice needs to be further studied.

A multicolor immunosensor for the visual detection of six sulfonamides based on manganese dioxide nanosheet-mediated etching of gold nanobipyramids.

In reality, various sulfonamides (SAs) were alternately used in animal husbandry to avoid generating drug resistance. Thus, it is crucial to develop simple and high-throughput methods for detecting multiple or groups of SAs to realize rapid screening of total SAs residues in foods. We herein developed a sensitive and efficient MnO2 nanosheets-mediated etching of gold nanobipyramids (AuNBPs), which can generate more vivid color changes, and further fabricated a high-throughput multicolor immunosensor for the visual screening/semi-quantitative detection of 6 different SAs including sulfamethazine (SMZ), sulfamethoxydiazine (SMD), sulfisomidine (SIM), sulfamerazine (SMR), sulfamonomethoxine (SMM) and sulfaquinoxaline (SQ) by using AuNBPs as signal and broad-specificity anti-SAs antibody as a bio-receptor. The immunosensor displays more vivid color changes, and has a lower visual detection limit and excellent specificity. It can be applied to detect as little as 1.0 ng/mL of SMZ, SMD, SMR and 2.0 ng/mL of SIM, SMM, SQ by bare eye observation, and 0.2 ng/mL of above 6 SAs by UV-visible spectrophotometry. The visual detection limit of the immunosensor is much lower than the maximum residue limit of total SAs (100 µg/kg) in edible tissues. The immunosensor was successfully applied to detect SMZ, SMD, SIM, SMR, SMM and SQ in milk with a recovery of 84%-106% and a RSD (n = 5) < 8%. The success of this study provided a promising assay for the on-site rapid screening of SMZ, SMD, SIM, SMR, SMM and SQ in food by bare eye observation. Importantly, the immunosensor may be expended as a general method for the visual screening/semi-quantitative detection of the group of other antibiotics by using the corresponding broad-specificity antibody as a bio-receptor.

Identification of risk and prognostic factors for intrahepatic vascular invasion in patients with hepatocellular carcinoma: a population-based study.

Background: The aim of this study was to develop nomograms to predict the risk of intrahepatic vascular invasion (IVI) of hepatocellular carcinoma (HCC) patients and estimate the overall survival (OS) and cancer-specific survival (CSS) of HCC patients with IVI. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with HCC from 2010 to 2015. Ultimately, 1,287 HCC patients with IVI were included in this study and randomly divided into training (n=901) and validation (n=386) cohorts. Multivariate logistic regression analysis and multivariate Cox proportional hazards regression analysis were performed to construct nomograms to visually quantify the risk of IVI in patients with HCC and predict the prognosis. The prediction effect of nomograms was evaluated using Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA), respectively. Results: The C-index of the nomogram for risk prediction was 0.730. The C-indices based on the nomogram were 0.762 [95% confidence interval (CI): 0.745-0.779] and 0.770 (95% CI: 0.753-0.787) for OS and CSS prediction in the training cohort, respectively. In the validation cohort, the C-indices were 0.779 (95% CI: 0.752-0.806) and 0.795 (95% CI: 0.768-0.822) for OS prediction and CSS prediction, respectively. Overall, the ROC curve, calibration plots, and DCA indicated the good performance of nomograms. Conclusions: We identified the relevant risk and prognostic factors for IVI in patients with HCC. The nomograms performed well on validation and may help to facilitate clinical decision-making.

TOP2A inhibition reverses drug resistance of hepatocellular carcinoma to regorafenib.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death attributed to high frequency of metastasis and multiple drug resistance. We aim to examine the underlying molecular mechanism and to seek potential strategies to reverse primary/acquired resistance to regorafenib. Topoisomerase IIα (TOP2A) is critical for tumorigenesis and carcinogenesis. Clinically, high-TOP2A expression was correlated to shorter overall survival (OS) of patients, but its role in drug resistance of HCC remains unknown. Here, we screened the expression profiling of TOP2A in HCC and identified TOP2A as an upregulated gene involved in the resistance to regorafenib. Sustained exposure of HCC cells to regorafenib could upregulate the expression of TOP2A. Silencing TOP2A enhanced HCC cells' sensitivity to regorafenib. TOP2A inhibition by doxorubicin or epirubicin synergized with regorafenib to suppress the growth of sorafenib-resistant HCC tumors that possessed the sorafenib-resistant features both in vitro and in vivo. Thus, targeting TOP2A may be a promising therapeutic strategy to alleviate resistance to regorafenib and thus improving the efficacy of HCC treatment.

Research on the Time Drift Stability of Differential Inductive Displacement Sensors with Frequency Output.

An edge displacement sensor is one of the key technologies for building large segmented mirror astronomical optical telescopes. A digital interface is one novel approach for sensor technologies, digital transformation and the Internet of Things (IoT) in particular. Frequency output sensors and inductance-to-digital converter (LDC) demonstrated significant advantages in comparison with conventional sensors with analog-to-digital converter (ADC) interfaces. In order for the differential inductive frequency output displacement (DIFOD) sensor to meet the high-stability requirements of segmented mirror astronomical telescopes, it is important to understand the factors for time drift of the sensor. This paper focuses on the investigation of key factors of sensor structure and material, signal conditioning and interface, and fixtures for time drift to permanently installed applications. First, the measurement principle and probe structural characteristics of the sensor are analyzed. Then, two kinds of signal conditioning and digitalization methods using resonance circuits and LDC chips are implemented and compared. Finally, the time drift stability experiments are performed on the sensors with different signal conditioning methods and fixtures under controlled temperature. Experimental results show that the magnetic shield ring effectively improves the sensitivity and quality factor of the sensors, the time drift stability of the sensor using the signal conditioning based on resonance circuits is better than that of the sensors using LDC chips, and the root mean square (RMS) of the sensor time drift meets the requirement of 0.01 µm/24 h. This study will help further development of high-stability of frequency output sensors and IoT-based systems for scaled-up applications in the future.

Series-temporal transcriptome profiling of cotton reveals the response mechanism of phosphatidylinositol signaling system in the early stage of drought stress.

Plants are sessile organisms suffering severe environmental conditions. Drought stress is one of the major environmental issues that affect plant growth and productivity. Although complex regulatory gene networks of plants under drought stress have been analyzed extensively, the response mechanism in the early stage of drought stress is still rarely mentioned. Here, we performed transcriptome analyses on cotton samples treated for a short time (10 min, 30 min, 60 min, 180 min) using 10% PEG, which is used to simulate drought stress. The analysis of differently expressed genes (DEGs) showed that the number of DEGs in roots was obviously more than that in stems and leaves at the four time points and maintained >2000 FDEGs (DEGs appearing for the first time) from 10 min, indicating that root tissues of plants respond to drought stress quickly and continuously strongly. Gene ontology (GO) analysis showed that DEGs in roots were mainly enriched in protein modification and microtubule-based process. DEGs were found significantly enriched in phosphatidylinositol signaling system at 10 min through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, implying the great importance of phosphatidylinositol signal in the early stage of drought stress. What was more, two co-expression modules, which were significantly positively correlated with drought stress, were found by Weighted Gene Co-expression Network Analysis (WGCNA). From one of the co-expression modules, we identified a hub-gene Gohir.A07G058200, which is annotated as "phosphatidylinositol 3- and 4-kinase" in phosphatidylinositol signaling system, and found this gene may interact with auxin-responsive protein. This result suggested that Gohir.A07G058200 may be involved in the crosstalk of phosphatidylinositol signal and auxin signal in the early stage of drought stress. In summary, through transcriptome sequencing, we found that phosphatidylinositol signaling system is an important signal transduction pathway in early stage in response to drought stress, and it may interact with auxin signal transduction through phosphatidylinositol 3- and 4-kinase.

Colorimetric aptasensor for sensitive detection of quinclorac based on exonuclease III-assisted cyclic release of phosphorodiamidate morpholino oligomer mimic enzyme strategy.

Here, a colorimetric aptasensor was constructed for sensitively detecting quinclorac (QNC), a common herbicide. The aptasensor involved a novel amplification strategy and a classical strand displacement strategy. The amplification strategy, termed exonuclease III (Exo III)-assisted cyclic release of phosphorodiamidate morpholino oligomer (PMO) mimic enzyme strategy, was developed based on two new findings on PMO: 1) DNA hybridized with PMO could resist Exo III digestion; 2) a designed G-rich PMO (named P2) could bind to hemin to form a G-quadruplex PMOzyme with peroxidase-like activity. In this strategy, a designed DNA-PMO duplex (D1-P1) completely hybridized with DNA2 (D2) in the other designed DNA-PMO duplex (D2-P2) to trigger D2 degradation by Exo III and cyclic release of P2. After that, the hemin-binding P2 catalyzed colorless tetra-methyl benzidine (TMB) to blue TMB+. The cycle process was performed at high Exo III concentrations without strict control and with constant background signals. In that case, the developed strategy was sensitive, efficient, easy to operate, reliable, and ultralow background. Meanwhile, a QNC aptamer was used to develop the strand displacement strategy based on magnetic beads. The colorimetric aptasensor was sensitive and selective for QNC detection with a detection limit of 7.1 ng mL-1. It was successfully applied to detect QNC in soil and river water with good recovery rates (92-98%) and a relative standard deviation (n = 3) <5%. The success of this study could provide a general reference strategy for developing sensitive aptasensors and other nucleic acid-related sensors.

Paper-based multicolor sensor for on-site quantitative detection of 2,4-dichlorophenoxyacetic acid based on alkaline phosphatase-mediated gold nanobipyramids growth and colorimeter-assisted method for quantifying color.

On-site quantitative analysis of pesticides is important for food safety. Colorimetric gold nanobipyramids (AuNBPs) sensors are powerful methods for on-site detection. However, a single quantitative method and the instability of AuNBPs in solution limit the practicability of those sensors. Here, a paper-based multicolor AuNBPs sensor involved a colorimeter-assisted method for quantifying color was developed for quantitative detection of 2,4-dichlorophenoxyacetic acid (2,4-D), a common herbicide. The novelty of this study lies in developing a general paper-based quantitative on-site method (PQOM) for colorimetric AuNBPs sensors. Firstly, a paper-based analytical device (PAD) consisting of a nylon membrane, absorbent cotton layers, and two acrylic plates was fabricated to deposit AuNBPs. We demonstrated the PAD could improve the stability of AuNBPs and the detection sensitivity of AuNBPs sensors. Then, a handheld colorimeter was first used to quantify the color change of AuNBPs on the PAD based on the CIELab color space. Finally, as proof of concept, the PQOM was successfully employed to quantify 2,4-D by combining with an alkaline phosphatase-mediated AuNBPs growth method. In this method, 2,4-D specifically inhibited alkaline phosphatase activity to suppress the generation of l-ascorbic acid, thereby mediating AuNBPs growth. The developed sensor exhibited seven 2,4-D concentration-related colors and detected as low as 50 ng mL-1 2,4-D by naked-eye observation and 18 ng mL-1 2,4-D by a colorimeter. It was applied to detect 2,4-D in the spiked rice and apple samples with good recovery rates (91.8-112.0%) and a relative standard deviation (n = 5) < 5%. The success of this study provides a sensing platform for quantifying 2,4-D on site.

Polyamine-metabolizing enzymes are activated to promote the proper assembly of rice stripe mosaic virus in insect vectors.

Both viruses and host cells compete for intracellular polyamines for efficient propagation. Currently, how the key polyamine-metabolizing enzymes, including ornithine decarboxylase 1 (ODC1) and its antizyme 1 (OAZ1), are activated to co-ordinate viral propagation and polyamine biosynthesis remains unknown. Here, we report that the matrix protein of rice stripe mosaic virus (RSMV), a cytorhabdovirus, directly hijacks OAZ1 to ensure the proper assembly of rigid bacilliform non-enveloped virions in leafhopper vector. Viral matrix protein effectively competes with ODC1 to bind to OAZ1, and thus, the ability of OAZ1 to target and mediate the degradation of ODC1 is significantly inhibited during viral propagation, which finally promotes polyamines production. Thus, OAZ1 and ODC1 are activated to synergistically promote viral persistent propagation and polyamine biosynthesis in viruliferous vectors. Our data suggest that it is a novel mechanism for rhabdovirus to exploit OAZ1 for facilitating viral assembly.

Rice yellow stunt virus activates polyamine biosynthesis to promote viral propagation in insect vectors by disrupting ornithine decarboxylase antienzyme function.

Intracellular polyamines (putrescine, spermidine, and spermine) have emerged as important molecules for viral infection; however, how viruses activate polyamines biosynthesis to promote viral infection remains unclear. Ornithine decarboxylase 1 (ODC1) and its antienzyme 1 (OAZ1) are major regulators of polyamine biosynthesis in animal cells. Here, we report that rice yellow stunt virus (RYSV), a plant rhabdovirus, could activate putrescine biosynthesis in leafhoppers to promote viral propagation by inhibiting OAZ1 expression. We observed that the reduction of putrescine biosynthesis by treatment with difluormethylornithine (DFMO), a specific nontoxic inhibitor of ODC1, or with in vitro synthesized dsRNAs targeting ODC1 mRNA could inhibit viral infection. In contrast, the supplement of putrescine or the increase of putrescine biosynthesis by treatment with dsRNAs targeting OAZ1 mRNA could facilitate viral infection. We further determined that both RYSV matrix protein M and ODC1 directly bind to the ODC-binding domain at the C-terminus of OAZ1. Thus, viral propagation in leafhoppers would decrease the ability of OAZ1 to target and mediate the degradation of ODC1, which finally activates putrescine production to benefit viral propagation. This work reveals that polyamine-metabolizing enzymes are directly exploited by a vector-borne virus to increase polyamine production, thereby facilitating viral infection in insect vectors.

The clinical characteristics of cataplectic attack in narcolepsy type 1.

OBJECTIVE: Cataplexy is a pathognomonic symptom of narcolepsy type 1. This study was conducted to clarify the clinical characteristics of cataplexy by staging, and to further analyse the correlations of clinical features and cataplectic stages in patients with narcolepsy type 1 (NT1). METHODS: We experimentally triggered patients with NT1 into cataplexy while under video-polysomnography (v-PSG) monitoring in the sleep lab. The most serious cataplectic attack from each patient was analysed. Each cataplectic episode was segmented into four stages according to the v-PSG. Correlations were analysed between cataplectic stages in pairs, and between cataplectic stages and other clinical features. RESULTS: We observed 81 cataplectic episodes in 21 patients with diverse triggers, including humorous or exciting videos, tickling, recalling horrible memories and exercising. Nine patients (43%) went through complete cataplectic attacks while the others experienced partial attacks. Four cataplectic stages (ie, triggering, resisting, atonic, and recovering) were identified according to clinical and electromyograms characteristics. Resisting stage is predominant (56.4%) in cataplexy, while atonic stage is most related with the total duration of cataplexy. The Epworth Sleepiness Scale score (ESS) has a positive correlation with the total duration of cataplexy. Both duration of cataplexy and ESS score are negatively correlated with disease course. However, medication history seems have no influence on either cataplexy duration or ESS score. CONCLUSION: Four-stage segmentation shows the dynamic process of the cataplectic attack, which is different from the traditional classification of complete or partial cataplexy. Resisting stage is necessary for every cataplexy and might reflect the compensation mechanism, while atonic stage may be omitted in some patients. The severity of narcolepsy reduces with the extension of natural course regardless of medication history.

Multicolor visual screening of total dithiocarbamate pesticides in foods based on sulfydryl-mediated growth of gold nanobipyramids.

Dithiocarbamates (DTCs) pesticides were extensively used as fungicides in a variety of crops during their growth, storage and shipment. The DTCs residue in foods will seriously harm human health. In this study, a novel multicolor colorimetric sensor was developed for visual screening of total DTCs (total of ziram, thiram and zineb) based on sulfhydryl-mediated growth of gold nanobipyramids (AuNBPs). We demonstrated that DTCs can absorb on AuNBPs seed's surface via the formation of Au-S bonds and thus impede the 8-hydroxyquinoline (8-HQ)-promoted AuNBPs growth, which generates DTCs concentration-corresponding color changes. The developed sensor has vivid color changes, short analysis time, higher sensitivity and excellent specificity. It can be used to detect as low as 50 nM of total DTCs by bare eye observation and 17-18 nM of total DTCs by UV-visible spectrometry. By using the multicolor sensor, we have successfully screened total DTCs in apple and black tea by bare eye observation, and detected total DTCs in apple and black tea by UV-visible spectrometry with a recovery of 90%-104% and a relative standard deviation (RSD, n = 5) < 5%. The results obtained with our method consisted well with those obtained with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), verifying that our method had good accuracy and reliability. Especially, the visual detection limit of our method is much lower than the maximum residue limit of total DTCs in vegetable and fruits. All above features make our sensor a promising method for rapid on-site screening of total DTCs in vegetable and fruits by only bare eye observation.

D-penicillamine modified copper nanoparticles for fluorometric determination of histamine based on aggregation-induced emission.

A fluorometric method for the determination of histamine has been developed based on aggregation-induced emission (AIE) effect of D-penicillamine capped copper nanoparticles (DPA-CuNPs). The fluorescent DPA-CuNPs were synthesized by a one-pot method using D-penicillamine as both reducing agent and stabilizing ligand. The size, morphology and physical chemical properties of DPA-CuNPs were examined by transmission electron microscopy (TEM), fluorescence spectroscopy, fourier transform infrared spectroscopy (FTIR) and absorption spectroscopy. The DPA-CuNPs exhibit AIE effect and show intense red fluorescence (650 nm). In the presence of histamine, DPA-CuNPs are dispersed into small homogeneous particles, causing fluorescence quenching. Based on this reaction, a histamine sensor is constructed. The fluorescence of the CuNPs solution has a good linear relationship with histamine concentration in the range 0.05 µM to 5 µM and the determination limit (3σ/slope) is 30 nM. The estimated method was successfully applied to the determination of histamine in fish, pork and red wine. Graphical abstract Schematic representation of copper nanoparticles for histamine analysis. In the presence of histamine, the strong red fluorescence of copper nanoparticles is obvious decreased through interaction of copper nanoparticles and histamine.

Integrated analysis of miRNA and mRNA expression in the blood of patients with Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, which is considered the most common type of dementia worldwide. The aim of the present study was to identify key microRNAs (miRNAs/miRs) and mRNAs affecting the pathogenesis of AD, which may be developed as promising biomarkers for the early diagnosis or targeted therapy of patients with AD. Integrative analysis was performed on 12 representative miRNA datasets and three mRNA datasets of the blood from patients with AD, in order to identify differentially expressed (DE)miRNAs and DEmRNAs. Subsequently, the miRWalk database was used to identify the potential miRNA­mRNA interactions among DEmiRNAs and DEmRNAs, and an AD­specific miRNA­mRNA network was constructed using Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to assess the target mRNAs of DEmiRNAs. A total of 37 DEmiRNAs and 2,011 DEmRNAs were identified between AD and normal control samples. In addition, 853 high confidence miRNA­mRNA interactions were identified and subsequently used to construct the AD specific miRNA­mRNA network. A total of five miRNAs, including hsa­miR­93, hsa­miR­26b, hsa­miR­34a, hsa­miR­98­5p and hsa­miR­15b­5p were identified as the key nodes in the miRNA­mRNA network by topological analysis. Functional enrichment analysis demonstrated that the target mRNAs of DEmiRNAs were enriched in AD­associated pathways, such as the 'neurotrophin signaling pathway' and 'insulin signaling pathway'. Taken together, the results of the present study provide novel insights into the molecular mechanisms underlying AD and contribute to the identification of biomarkers and novel strategies for drug design for AD treatment.

A Multicolor Immunosensor for Sensitive Visual Detection of Breast Cancer Biomarker Based on Sensitive NADH-Ascorbic-Acid-Mediated Growth of Gold Nanobipyramids.

Many studies have demonstrated that the extracellular domain of human epidermal growth factor receptor 2 (HER2 ECD) level in serum can act as a breast cancer biomarker and serve as a monitoring neoadjuvant therapy of breast cancer. In this study, we developed a sensitive ascorbic acid (AA)-mediated AuNBPs (gold nanobipyramids) growth method with NADH (reduced nicotinamide adenine dinucleotide I) assistance, and we further fabricated a high-resolution multicolor immunosensor for sensitive visual detection of HER2 ECD in serum by using AuNBPs as signal and antibody as recognition probe. The NADH-assisted AA-mediated method effectively suppressed color formation in the blank and greatly improved the sensitivity of mediating AuNBPs growth, allowing us to use a low concentration of AA to mediate AuNBPs growth to generate more colorful and clearer color changes. The proposed multicolor immunosensor has higher resolution and more color changes corresponding to HER2 ECD concentrations. It can be used to detect as low as 0.5 ng/mL of HER2 ECD by bare eye observation and 0.05 ng/mL of HER2 ECD by UV-visible spectrophotometry. Using the immunosensor, we have successfully detected HER2 ECD in human serum with a recovery of 94%-96% and an RSD (n = 5) < 5%. The results obtained with our immunosensor were consistent with those obtained with ELISA, verifying the immunosensor has good accuracy. The immunosensor exhibited a vivid multicolor change, has low visual detection limit, excellent specificity and reproducibility, and robust resistance to matrix. All the above features makes our immunosensor a promising assay for the early diagnosis of HER2-dependent breast cancers in clinical diagnosis.

The effect of different flushing methods in a short peripheral catheter.

PURPOSE: To develop a rabbit model of a short peripheral catheter (SPC) and to observe the effects of different flushing methods on blood vessels. METHODS: Thirty rabbits were randomly divided into three groups (A, B, and C), with ten rabbits per group. In group A, we used pulsed flush; in group B, we used uniform flush; and no treatment was used in group C. RESULTS: We observed that a uniform flush reduced blockage, phlebitis, and exudation compared to a pulsed flush by visual observation. The histopathological examination found that the morphological changes in group A were more severe than in group B and C related to loss of venous endothelial cells, inflammatory cell infiltration, edema, epidermal and chondrocyte degeneration, except for the thrombosis on group B that was more serious than in group A, especially in the distal side of puncture points. The distal region of groups A and B had more inflammatory cell infiltration than the proximal region. Thrombosis was more severe in the distal region than in the proximal region in group B. CONCLUSIONS: The uniform flush produced less damage to the vascular endothelium and surrounding tissues and was superior to the pulsed flush. However, the uniform flush is prone to thrombosis.