Fluorescent immunochromatography of vancomycin in plasma: A rapid and sensitive quantitative analysis.

Vancomycin (VAN) has a narrow therapeutic window and variable pharmacokinetic properties, which require timely monitoring of plasma concentration to adjust the dosage for better effectiveness. A sensitive and quantitative immunochromatographic method was developed to detect VAN in plasma. The linear response range of the method to detect plasma VAN was 1.25-50 µg/mL. The intra- and inter-assay coefficients were 4.68% and 8.81%, respectively, while the recovery was 89.10%-98.32%. The clinical comparative experiment results demonstrated a good correlation (r > 0.90) between the fluorescent immunochromatographic strip test and the mass spectrum. In this study, a simple, rapid, and high-sensitivity immunochromatographic method was established for detecting VAN, which helped establish the basis for further application of monitoring plasma concentration.

Overcoming Hypoxia-Restrained Radiotherapy Using an Erythrocyte-Inspired and Glucose-Activatable Platform.

Radiotherapy (RT) as one of the most powerful cancer treatment strategies has been greatly restricted by tumor hypoxia. A mounting effort has been devoted to develop oxygen delivery systems for boosting the RT effect. Unluckily, those systems only supplied modest oxygen, which could not afford more than once and long-time RT. Herein, we describe the development of a glucose-regulated drug release platform, allowing for a long-term tumor normoxic microenvironment and repeated RT for a long time. The repeated cycles resulted in sustained high Endostar plasma levels, which dramatically normalized the tumor vasculature and chronically reversed tumor hypoxia. Taking advantage of the inexhaustible supply of oxygen, Endo@GOx-ER enabled RT achieved an impressive cancer treatment output. To the best of our knowledge, our strategy is the initial attempt to overcome tumor-hypoxia-limited RT through the normalization of tumor vasculature by using an erythrocyte-inspired and glucose-activatable platform and it visually casts a light on the clinical development.

An electrochemical biosensor based on multi-wall carbon nanotube-modified screen-printed electrode immobilized by uricase for the detection of salivary uric acid.

The amounts of uric acid (UA) in non-invasive biological samples, such as saliva, are critical for diagnosis and therapy of gout, hyperuricemia, Lesch-Nyhan syndrome, and several other diseases. Here, disposable UA biosensors were fabricated with the screen printing technique on the substrate of flexible PET. The working electrode was modified with carbon nanotubes followed by uricase for UA detection with excellent selectivity. The biosensor showed good electrocatalytic activity toward UA with high sensitivity, low detection limit, and wide linear range, which covers the full range of UA levels in human saliva. We demonstrate that UA can be directly detected in human saliva with the biosensor and the experimental data were consistent with the clinical analysis. This study indicated that the non-invasive biosensor is an attractive and possible approach for the monitoring of salivary UA. Graphical abstract A disposable uric acid biosensor modified with carbon nanotubes followed by uricase was fabricated on flexible PET and applied for the monitoring of salivary uric acid in human saliva.

Climate change and mortality evolution in China.

This paper explores the historical relationship between weather fluctuations and mortality evolution in China. Using panel data on the annual provincial mortality rate and daily weather variables for the 1964-2008 period, we applied a dynamic model structure with sufficient controls to estimate the short-term effects of temperature shocks on China's mortality rate. Our main results show that an additional 1 °C rise in average temperature in a given year increases the annual mortality rate by an average of 3.2%. In addition, days with daily average temperatures exceeding 27 °C (30 °C) are associated with an increase in the annual mortality rate of nearly 0.1% (0.2%) or approximately 9,520 (19,040) additional deaths. In contrast, extremely cold days do not have these effects. By applying a hybrid model structure (the long difference approach) to examine the medium-term effects of temperature changes, we find that there is little evidence of overall adaptation to high temperatures when moving from the short term to the medium term. In addition, by introducing interactions between temperatures and potential modifiers such as access to doctors, hospital beds, air conditioning and refrigerators, we determined that only residential air conditioning played an important role in mitigating the temperature-mortality relationship. However, the penetration of air conditioning in China is still relatively low. These findings indicate that climate change could partially explain the historical phenomenon of China's rising mortality rate during the unprecedented economic boom experienced since the 1980s.

Electrochemically reduced graphene oxide and gold nanoparticles on an indium tin oxide electrode for voltammetric sensing of dopamine.

The authors describe an electrochemical dopamine sensor that is based on the use of electrochemically co-reduced graphene oxide (Er-GO) and gold nanoparticles (AuNPs) on an indium-tin oxide (ITO) electrode. The synergistic effects of Er-GO and Er-AuNPs promote electron transport in the modified ITO. This results in an excellent performance for voltammetric sensing of dopamine (DA). Under the optimum conditions and a typical working potential of -0.05 V (vs. Ag/AgCl), the ITO electrode has a linear response in the 0.02-200 µM DA concentration range and a low detection limit of 15 nM. The sensor also showed a good selectivity over ascorbic acid and uric acid. The feasibility of the method was studied by analyzing DA in cerebrospinal fluid of rats. Graphical abstract Schematic presentation of one-step electrochemical co-reduction of graphene oxide (GO) and gold nanoparticles (AuNPs) on an ITO electrode for voltammetric sensing of dopamine.

[Research progress on genotyping of Helicobacter pylori].

Helicobacter pylori (Hp) is widely disseminated in human, and Hp infection causes various gastrointestinal diseases, including gastric cancer. Different genotypes of Hp may cause different diseases, so the genotyping is important for clinical and basic research of Hp. This article introduces the methods for Hp genotyping, including multilocus sequence typing, pulsed-field gel electrophoresis, random amplified polymorphic DNA, amplified fragment length polymorphism, and whole-genome sequencing. By reviewing the application of these techniques in Hp genotyping and comparing their advantages and disadvantages, the article provides a theoretical basis for research into the pathogenesis, antibiotic resistance, and epidemiology of Hp infection.

Role of Flagella in the Pathogenesis of Helicobacter pylori.

This review aimed to investigate the role of Helicobacter pylori flagella on the pathogenicity of this bacterium in humans. Helicobacter pylori is a flagellated pathogen that colonizes the human gastroduodenal mucosa and produces inflammation, and is responsible for gastrointestinal disease. Its pathogenesis is attributed to colonization and virulence factors. The primary function of H. pylori flagella is to provide motility. We believe that H. pylori flagella play an important role in the colonization of the gastrointestinal mucosa. Therefore, we reviewed previous studies on flagellar morphology and motility in order to explore the relationship between H. pylori flagella and pathogenicity. Further investigation is required to confirm the association between flagella and pathogenicity in H. pylori.

Design, Synthesis, and Biological Activities of Novel Pyrazole Oxime Compounds Containing a Substituted Pyridyl Moiety.

In this paper, in order to find novel biologically active pyrazole oximes, a series of pyrazole oxime compounds bearing a substituted pyridyl unit were prepared. Bioassays showed that some target compounds were found to have good acaricidal activity against Tetranychus cinnabarinus at a concentration of 500 µg/mL, compound 9q especially displayed potent acaricidal activity against T. cinnabarinus when the concentration was reduced to 100 µg/mL. Interestingly, most target compounds possessed excellent insecticidal activities against Oriental armyworm at 500 µg/mL. Moreover, some compounds were active against Aphis medicaginis and Nilaparvata lugens at 500 µg/mL. Additionally, compounds 9b, 9g, 9l, 9p, 9q, 9r, 9s, 9t, 9u, and 9v displayed significant antiproliferative activities against HepG2 cells with IC50 values of 1.53-17.27 µM, better than that of the control 5-fluorouracil (IC50 = 35.67 µM).

Design, Synthesis and Bioactivities of Novel 1,4-Pentadien-3-one Derivatives Containing a Substituted Pyrazolyl Moiety.

In this study, in order to find novel biologically active penta-1,4-dien-3-one derivatives, a series of penta-1,4-dien-3-one compounds containing a substituted pyrazole subunit were designed and synthesized. Their structures were characterized by ¹H-NMR, 13C-NMR and elemental analysis. The preliminary bioassays displayed that most of the title compounds showed significant antiproliferative activity against HepG2 cell lines. Especially, compounds 7a-m, o, r, s, u, w, y and z were active against HepG2 cells with IC50 values of 0.10-5.05 µM, which were superior to that of the contrast sorafenib (IC50 = 16.20 µM).

Effect of "phase change" complex on postoperative adhesion prevention.

BACKGROUND: Postsurgical peritoneal adhesion is a major clinical problem. Numerous anti-adhesion products have been studied, but none could be easily used to provide a physical barrier. In this study, we developed a "phase change" anti-adhesion barrier for reducing peritoneal adhesion by cross-linked copolymerization of O-carboxymethyl chitosan (CMC) and CaCl2 and addition of cyclosporin A (CsA). MATERIALS AND METHODS: The CMC-CaCl2-CsA compound was characterized by equilibrium swelling rate, weight loss, releasing effect, and coagulation test, and its biosafety was characterized by acute oral toxicity, hemolysis, and cytotoxicity. Intestinal adhesion model was applied on 64 Sprague-Dawley rats, which received CMC, CMC-CaCl2, or CMC-CaCl2-CsA treatment. At postoperative days 7 and 14, the rats were euthanized, and adhesions were graded by an investigator blinded to the treatment groups, using a predetermined adhesion scoring system. The cecum and adhesion tissue were stained with hematoxylin and eosin and antibodies for matrix metalloproteinase-9 and TIMP-1 for further histopathologic examination. RESULTS: The phase change anti-adhesive material exhibited effective blood clotting and were nontoxic in clotting experiments and acute toxicity test. The degradation rate could be adjusted using phosphate-buffered solution with varying pH. Adhesions were significantly reduced in the CMC-CaCl2-CsA treatment group compared with the control group (P < 0.001). Expression of matrix metalloproteinase-9 was stronger in CMC-CaCl2-CsA treatment group at 7 days after surgery. CONCLUSIONS: "Phase-change" adhesive can undergo changes after application, and it inhibits the formation of abdominal adhesions after surgery. The material is convenient for using by surgeons and provides an effective tool for intestinal adhesion prevention.

Fabrication of Waterproof, Breathable Composite Liquid Dressing and Its Application in Diabetic Skin Ulcer Repair.

OBJECTIVES: Diabetic patients are at increased risk of severe skin infections. Covering the wound as early as possible can prevent infection and shorten the course of treatment. In this study, the authors fabricated a waterproof and breathable composite liquid dressing (CLD) that formed a barrier to bacteria and shortened healing time of diabetic rat skin ulcers. METHODS: The CLD was prepared in a formulation that, on evaporation of the liquid carrier, acts as a waterproof, breathable coating on injured skin. The coating was analyzed for water resistance, moisture vapor transmission rate (MVTR), bacterial barrier properties, sustained-release function, and biosafety. A chemically induced rat model of diabetic foot ulcers was used to examine the wound healing effect of CLD and CLD that contained Dermlin (Yensen Biotech Co, Jiangyin, Jiangsu, China). The wound healing rate, histologic changes, and epidermal growth factor expression were also evaluated. RESULTS: The CLD functioned as an effective barrier against infection, was waterproof, had a suitable MVTR, and had effective biosafety. The synergistic effects of CLD and Dermlin had a rapid wound closure rate. Histologic analysis and measurement of epidermal growth factor expression through an in vivo test revealed that the possible mechanism of the CLD effects included the reduction of inflammation and promotion of cell proliferation. CONCLUSIONS: Early treatment with the CLD can prevent infection. In combination with Dermlin, the CLD may promote better wound closure in diabetic skin ulcers. The authors' study suggests a novel strategy for ulcer healing.

Paper-based cell impedance sensor and its application for cytotoxic evaluation.

Disposable analytical devices for developing sensitive and label-free monitoring of cancerous cells would be attractive for cancer research. Here, paper-based electroanalytical devices based on impedance spectrometry were applied for the study of K562 cells and the toxic effect of anticancer drugs. The proposed device integrating gold nanorods modified ITO electrodes could provide a biocompatible surface for immobilization of living cells maintaining their bioactivity. The impedance results exhibited good correlation to the logarithmic value of cell numbers ranging from 7.5 × 10(2) to 3.9 × 10(6) cells mL(-1) with a detection limit of 500 cells mL(-1). Furthermore, this strategy was used to evaluate the cytotoxic effects of arsenic trioxide and cyclophosphamide. Results obtained by the impedimetric method correlate well with the conventional cell viability assay. Cells exposed to drugs exhibited a prominent reduction of impedance data, showing an inverse dose-dependent relationship. This simple, cost-effective and portable paper-based electrochemical analytical device could provide a new impedance platform for applications in monitoring cell behavior, pharmacological studies and toxicological analyses.

Graphene oxide-modified electrodes for sensitive determination of diethylstilbestrol.

This paper reports an electrochemical sensor fabricated with graphene oxide (GO) modified on a chitosan-coated glassy carbon electrode (GO-CS/GCE) and its application for the detection of diethylstilbestrol (DES). It was observed that the effective electrochemical surface area of the GO modified electrode was nearly 10 times that of the bare GCE. This could be used to explain the results that the oxidation peak current of DES on the GO-CS/GCE was much larger than on the bare GCE. Under optimized conditions, the prepared electrode could be used to electrochemically detect DES according to the oxidation of the DES. Based on the technique of differential pulse voltammetry and the accumulation of DES on GO modified electrodes, the calibration curve for DES determination could be obtained with a linear range of 1.5 × 10(-8)-3.0 × 10(-5) M and an estimated detection limit of 3.0 × 10(-9) M (S/N = 3). The feasibility of the developed electrode for tablet sample analysis was investigated. Our investigation revealed that GO could significantly improve the analytical performance of electrochemical sensors.

High prevalence of Helicobacter pylori mixed infections identified by multilocus sequence typing in Ningbo, China.

This study used multilocus sequence typing (MLST) to investigate the prevalence of Helicobacter pylori (H. pylori) mixed infections and H. pylori mixed infections involving unrelated strains; and determined the phylogeographic groups of H. pylori recovered from patients in Ningbo, China. A total of 156 H. pylori isolates were obtained from a convenience sample of 33 patients with culture-positive H. pylori infection. MLST was used to classify 150 H. pylori clinical isolates and 12 methodological control strains (6 clinical isolates and 6 strains of American Type Culture Collection H. pylori) into 43 and 12 sequence types (STs), respectively. In this study, 246 new alleles and 53 new STs were identified by MLST. The prevalence of mixed infections was 41% (11/27). The prevalence of H. pylori mixed infections involving unrelated strains was 46% (5/11) and the prevalence of H. pylori mixed infections involving completely unrelated strains (strains with all 7 housekeeping genes different) was 36% (4/11). A phylogenetic tree was created to determine the evolutionary relationships between different strains. The STs in this study were clustered within the hspEAsia subgroup (98%) and hpEurope group (2%). H. pylori mixed infections were common in Ningbo, China. The H. pylori isolates belonging to the hpEurope group were recovered from three different biopsy samples in a native Chinese patient. Most of H. pylori strains colonizing the antrum, corpus, and duodenum bulb were homologous.

Quantum dot (QD)-modified carbon tape electrodes for reproducible electrochemiluminescence (ECL) emission on a paper-based platform.

Stable and sensitive electrochemiluminescence (ECL) detection relies on successful immobilization of quantum dots (QDs) on working electrodes. Herein, we report a new technique to apply double-sided carbon adhesive tape as the working electrode to improve the stability and reproducibility of QD-based ECL emission. CdS QD-modified electrodes were prepared by dropping and drying CdS QD suspension on the carbon adhesive tape supported by indium tin oxide (ITO) glass. The ECL detection was performed with the prepared electrode on a paper-based platform. We tested our system using H(2)O(2) of various concentrations and demonstrated that consistent ECL emission could be obtained. We attribute stable and reproducible ECL emission to the robust attachment of CdS QDs on the carbon adhesive tape. The proposed method could be used to quantify the concentration of dopamine from 1 µM to 10 mM based on the quenching effect of dopamine on ECL emission of CdS QD system using H(2)O(2) as the coreactant. Our approach addressed the problem in the integration of stable QD-based ECL detection with portable paper-based analytical devices. The similar design offers great potential for low-cost electrochemical and ECL analytical instruments.

How Does the Change of Information Source Affect Residents' Risk Attitudes?

Using data from the China Family Panel Studies (CFPS), this paper investigates the effects of Internet use on residents' risk attitudes. Both Generalized Ordered Logit Model and Logit model are used to identify the effects of Internet use. The results reveal an association between Internet use and increases in both subjective and objective risk preferences that remains even after we adjust for possible endogeneity. The heterogeneity analysis also reveals that these impacts are different among groups with different reasons for Internet use and different personal characteristics. Our study expands the research on the effects of Internet on people's concepts from the micro perspective and suggests that while promoting the application of information technology we should also pay attention to the individual characteristics of residents so that we can better share the "digital dividend" brought by the popularization of information technology in the whole society.

Comprehensive Analysis of NAC Genes Reveals Differential Expression Patterns in Response to Pst DC3000 and Their Overlapping Expression Pattern during PTI and ETI in Tomato.

NAC (NAM/ATAF/CUC) transcription factors belong to a unique gene family in plants, which play vital roles in regulating diverse biological processes, including growth, development, senescence, and in response to biotic and abiotic stresses. Tomato (Solanum lycopersicum), as the most highly valued vegetable and fruit crop worldwide, is constantly attacked by Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), causing huge losses in production. Thus, it is essential to conduct a comprehensive identification of the SlNAC genes involved in response to Pst DC3000 in tomato. In this study, a complete overview of this gene family in tomato is presented, including genome localization, protein domain architectures, physical and chemical features, and nuclear location score. Phylogenetic analysis identified 20 SlNAC genes as putative stress-responsive genes, named SSlNAC 1-20. Expression profiles analysis revealed that 18 of these 20 SSlNAC genes were significantly induced in defense response to Pst DC3000 stress. Furthermore, the RNA-seq data were mined and analyzed, and the results revealed the expression pattern of the 20 SSlNAC genes in response to Pst DC3000 during the PTI and ETI. Among them, SSlNAC3, SSlNAC4, SSlNAC7, SSlNAC8, SSlNAC12, SSlNAC17, and SSlNAC19 were up-regulated against Pst DC3000 during PTI and ETI, which suggested that these genes may participate in both the PTI and ETI pathway during the interaction between tomato and Pst DC3000. In addition, SSlNAC genes induced by exogenous hormones, including indole-3-acetic acid (IAA), abscisic acid (ABA), salicylic acid (SA), and methyl jasmonic acid (MeJA), were also recovered. These results implied that SSlNAC genes may participate in the Pst DC3000 stress response by multiple regulatory pathways of the phytohormones. In all, this study provides important clues for further functional analysis and of the regulatory mechanism of SSlNAC genes under Pst DC3000 stress.

A Closed-Loop Autologous Erythrocyte-Mediated Delivery Platform for Diabetic Nephropathy Therapy.

Failure to control blood glucose level (BGL) may aggravate oxidative stress and contribute to the development of diabetic nephropathy (DN). Using erythrocytes (ERs) as the carriers, a smart self-regulatory insulin (INS) release system was constructed to release INS according to changes in BGLs to improve patients' compliance and health. To overcome the limited sources of ERs and decrease the risk of transmitting infections, we developed an in vitro, closed-loop autologous ER-mediated delivery (CAER) platform, based on a commercial hemodialysis instrument modified with a glucose-responsive ER-based INS delivery system (GOx-INS@ER). After the blood was drained via a jugular vein cannula, some of the blood was pumped into the CAER platform. The INS was packed inside the autologous ERs in the INS reactor, and then their surface was modified with glucose oxidase (GOx), which acts as a glucose-activated switch. In vivo, the CAER platform showed that the BGL responsively controlled INS release in order to control hyperglycemia and maintain the BGL in the normal range for up to 3 days; plus, there was good glycemic control without the added burden of hemodialysis in DN rabbits. These results demonstrate that this closed-loop extracorporeal hemodialysis platform provides a practical approach for improving diabetes management in DN patients.

Identification of nanoparticle-mediated siRNA-ASPN as a key gene target in the treatment of keloids.

Background: Keloid, also known as connective tissue hyperplasia, is a benign proliferative disorder with a global distribution. The available therapeutic interventions are steroid injections, surgical removal of keloids, radiotherapy, compression therapy, the application of cryosurgery, and many other methods. Objectives: Existing treatments or approaches for keloids may lead to similar or even larger lesions at the site of keloid excision, leading to a high recurrence rate. Therefore, this study aims at identifying a new gene-based therapy for the treatment of keloids. Methods: An ASPN-siRNA/nanoparticle combination (si-ASPN) and a negative siRNA/nanoparticle complex (NC) was developed on the basis of bioinformatics studies and used in vitro and in vivo experiments. Results: The results showed a strong correlation between the development of keloids and high expression of ASPN protein. With the expression of ASPN protein greatly reduced in keloid fibroblasts and nude mice allografts after treatment with si-ASPN, the collagen and fibroblasts were also uniform, thinner, parallel and regular. Conclusion: All the above experimental results suggest that keloid and ASPN are closely related and both fibroblast growth and metabolism of keloid are inhibited after silencing ASPN. Therefore, ASPN-siRNA delivered via nanoparticles can serve as a novel intervention therapy for the treatment of keloids.

Erythrocyte-mimicking subcutaneous platform with a laser-controlled treatment against diabetes.

Exogenous insulin (INS) is critical for managing diabetes. However, owing to its short in vivo half-life, frequent injection of INS is un-avoidable, which is both painful and inconvenient, compromising the quality of life. Herein, we developed a laser-regulated INS release system (INS-ICG@ER hydrogel) that allowed an on-demand release of INS from the subcutaneous INS reservoir by remote laser control without the frequent injection of INS. The amino acid hydrogel functions as a hydrogel 3D scaffold material, which offers increased subcutaneous stability of drug loaded erythrocytes (ER). This INS-ICG@ER hydrogel would release INS due to the elevated content of reactive oxygen species (ROS), generated by ICG under laser irritation. Conversely, the ROS would be scavenged without the laser irradiation and stopped the release of INS from INS-ICG@ER hydrogel. Furthermore, the release of INS from INS-ICG@ER hydrogel could be regulated by laser irradiation. The INS-ICG@ER hydrogels could control the hyperglycemia within 2 h in diabetic mice and maintained their normal blood glucose level (BGL) for up to 6 days with laser irradiation 30 min prior to meals avoiding the frequent injection of free INS. This delivery system is an effective method that offers a spatiotemporally controlled release of INS to control the glucose level in vivo.