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.

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.

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.

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.

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.

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.

Preparation of nanostructured PDMS film as flexible immunosensor for cortisol analysis in human sweat.

This work proposed a novel and flexible immunosensor for highly selective and sensitive determination of cortisol in sweat. The flexible electrode was developed by transferring multi-walled carbon nanotubes (MWCNTs) film on polydimethylsiloxane (PDMS) substrate and subsequent electrochemical deposition of Au nanoparticles (AuNPs) on the MWCNTs surface. The obtained AuNPs/MWCNTs/PDMS electrode was then covalently immobilized with anti-cortisol monoclonal antibody (Anti-Cmab) and blocked with BSA. Scanning electron microscope confirmed that MWCNTs have been firmly combined with PDMS and AuNPs distributed uniformly on the surface of MWCNTs. The PDMS-based sensor possesses a good mechanical stability against stretching, bending and twisting, displaying stable electrochemical performance under deformation. After optimizing the analytical parameters, the developed immunosensor allowed a facile quantification of cortisol in the range of 1 fg/mL-1 µg/mL with a detection limit of 0.3 fg/mL. The cortisol immunosensor was further used to evaluate cortisol levels in human sweat, and the results corresponded closely with commercially available chemiluminescence immunoassay (CLIA) method. Results indicated that the new cortisol immunosensor could provide an effective tool for the noninvasive, point of care measurement of sweat cortisol levels and is promise to be a wearable biosensor for the healthy monitoring.

Bi-enzymes treatments attenuate cognitive impairment associated with oxidative damage of heavy metals.

Oxidative stress has been implicated in the pathogenesis of cognitive impairment. Lead (Pb) is a common environmental toxicant and plays a vital role in oxidative stress activation. In this study, a superoxide dismutase (SOD) and catalase (CAT) containing poly (lactic-co-glycolic acid) (PLGA) meso-particles (PLGA@SOD-CAT) were prepared to attenuate cognitive impairment via inhibiting oxidative stress in rats. It was prepared using a double emulsion (water/oil/water phase) technique to minimize the hazardous effects of Pb burden on cognitive impairment. The meso-particles antagonized the Pb-induced cognitive impairments. Behaviour, serum biochemical parameters and biomarkers of oxidative stress in rats were evaluated after they were subjected to intravenous injection with lead nitrate and PLGA@SOD-CAT. Moreover, the potential protective mechanism of PLGA@SOD-CAT was determined. Notably, PLGA@SOD-CAT appreciably agented memory impairment caused by lead nitrate and it could significantly inhibit Pb-induced oxidative stress in the blood. Furthermore, a remarkable reversion effect of cognitive impairments, including escape latency, crossing platform times and time per cent during the platform quadrant, after PLGA@SOD-CAT administration were noted. Therefore, these results suggested that the bi-enzymes platform was a superior product in eliminating Pb-induced cognitive impairments through reducing expression of Pb-associated oxidative stress, and it could potentially be applied in detoxifying heavy metals in blood circulation.

Microfluidic Devices for Monitoring the Root Morphology of Arabidopsis Thaliana in situ.

Plant roots play critical roles in absorbing nutrients for the growth and development of plants as well as adapting different environments. Currently, there is no satisfactory way to track dynamic information when studying roots at the high temporal and spatial resolution. Herein, a simple microfluidic device with crossed microchannels was utilized for a microscopic investigation of Arabidopsis thaliana roots in situ. Our experimental results showed that the microfluidic system combined with a microscope could be conveniently utilized for the quantification of primary roots and root hairs with a change of micrometers within a time of minutes. Using the same approach, the influences of high salinity stress could also be investigated on different parts of roots, including the root cap, meristematic zone, elongation zone, mature zone, and root hairs. More importantly, the growth of roots and root hairs could be quantified and compared in a solution of abscisic acid and indole-3-acetic acid, respectively. Our study suggested that the microfluidic system could become a powerful tool for the quantitative investigation of Arabidopsis thaliana roots.

Au-Hemoglobin Loaded Platelet Alleviating Tumor Hypoxia and Enhancing the Radiotherapy Effect with Low-Dose X-ray.

Radiotherapy (RT) is a widely explored clinical modality to combat cancer. However, its therapeutic efficacy is not always satisfied because of the severe hypoxic microenvironment in solid tumors and the high dosage of radiation harmful to the adjacent healthy tissue. Herein, Au nanoparticle-hemoglobin complex nanoparticle loaded platelets (Au-Hb@PLT) were fabricated. These Au-Hb@PLT would be activated by tumor cells, and the formed platelet-derivate particles (PM) could deliver Au nanoparticle-hemoglobin complex deeply into tumor tissue because of their small size and tumor homing ability. Hemoglobin acts as an oxygen carrier to relieve the hypoxia and gold nanoparticles work as radiosensitizers to potentiate the sensitivity of tumor cells to X-ray, thus, enhancing the in vivo therapeutic outcome even under a low-dose RT in tumor bearing mice. The enhanced antitumor effect and survival benefits endowed by the Au-Hb@PLT were confirmed in vitro and in vivo. These results demonstrate that these Au-Hb@PLT can work as an oxygen vehicle, offer a promising approach to mitigate hypoxia and improve RT efficacy with a low RT dosage.

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.

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.

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.

Determination of salivary uric acid by using poly(3,4-ethylenedioxythipohene) and graphene oxide in a disposable paper-based analytical device.

We developed a paper-based analytical device based on the electropolymerization of poly (3,4-ethylenedioxythipohene) (PEDOT) and graphene oxide (GO) composites on the ITO substrate for the detection of uric acid (UA) in authentic human saliva. Scanning electron microscopy, UV-vis spectrum and X-ray diffraction confirmed the formation of porous PEDOT combined with GO film during the electropolymerization process. The nanocomposite based sensor showed an enhanced electrocatalytic activity toward UA with high sensitivity and stability. We demonstrate that UA can be directly detected in undiluted saliva using the paper-based electroanalytical device with no interference from ascorbic acid and dopamine that are normally present in biological fluids. The results indicated that the developed device is promising for non-invasive monitoring of salivary UA in human body.

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.

Fabrication and evaluation of hemoglobin-based polydopamine microcapsules as oxygen carriers.

Polydopamine-hemoglobin (PDA-Hb) microcapsules as suitable oxygen carriers are fabricated easily by templating decomposable MnCO3 particles in collaboration with self-polymerization of dopamine on pure Hb spheres. The PDA-Hb microcapsules possess a high oxygen affinity and are able to bind and release oxygen reversibly as demonstrated by electrochemical methods.

Ultrafast glucose-responsive, high loading capacity erythrocyte to self-regulate the release of insulin.

Insulin (INS) delivery system that can mimic normal insulin secretion to maintain the blood glucose level (BGL) in the normal range is an ideal treatment for diabetes. However, most of the existing closed-loop INS delivery systems respond slowly to the changes in BGL, resulting in a time lag between the abnormal BGL and the release of INS, which is not suitable for practical application. In this study, glucose oxidase (GOx)-modified erythrocytes are used as INS carriers (GOx-INS-ER) that can rapidly self-regulate the release of INS upon the changes in BGL. In this system, glucose can be broken down into gluconic acid and hydrogen peroxide by GOx-INS-ER, and the latter will rupture the erythrocyte membrane to release INS within minutes. A pulsatile release of INS can be achieved upon the changes in the glucose concentration. This GOx-INS-ER enables diabetic rats to overcome hyperglycemia within 1 h, and a single injection of this GOx-INS-ER into the STZ-induced diabetic rats can maintain the BGL in the normal range up to 9 days. STATEMENT OF SIGNIFICANCE: Diabetes mellitus has been a major public health threatener with global prevalence. Although, glucose-responsive carriers that can release insulin (INS) in a closed loop have been explored greatly in recent years, their sluggish glucose-responsive property and low INS-loading content greatly restrict their practical application [ACS Nano, 2013, 7, 4194]. In this work, we reported INS-loaded erythrocytes featuring ultrafast glucose-responsive property and high INS loading content, which could release INS in a closed loop. These GOX-INS-ERs could respond to the changes in glucose level within several minutes and self-regulate the release of INS for a long time. Single injection of GOX-INS-ER can overcome hyperglycemia in diabetic mice within 1 h and maintain the baseline level of glucose up to 9 days. We think our method may provide a robust way to potentiate diabetes treatment.

Extracorporeal magnetic approach to reduce the unwanted side-effects and improve antibacterial activity of Ag/Fe3 O4 nanocomposites in rat.

While Ag nanoparticles hold great promise for broad spectrum antibacterial activity, the potential risks of Ag nanoparticles (NPs) on human health remain a challenge. In this study, Ag/Fe3 O4 composites have been successfully prepared and characterized by transmission electron microscopy, X-ray powder diffraction, and Fourier-transform infrared spectroscopy, and their magnetic and antibacterial properties have been assessed. In vivo results show that the antibacterial effect of 500 µg/mL Ag/Fe3 O4 nanocomposites was significantly higher than that of 1000 µg/mL AgNPs after 72 h of treatment (p < 0.01). Hematoxylin and eosin (HE) staining showed that squamous epithelium and dermis collagen fibers formed in the Ag/Fe3 O4 group after 8 days treatment. Wound closure was significantly better for the Ag/Fe3 O4 group than for the AgNPs group. On the other hand, there was less Ag in blood, liver, and kidney in the Ag/Fe3 O4 group, as more Ag was retained in the wound. According to lactate dehydrogenase, γ-glutamyl transpeptidase, and reactive oxygen species results, Ag/Fe3 O4 nanocomposites caused less unwanted side-effects. This work presents a new paradigm to reduce the unwanted side-effects of AgNPs and improve their antibacterial activity, providing a new avenue for wound healing. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2029-2036, 2018.