Simplified Head-to-Tail Cyclic Polypeptides as Biomaterial-Associated Antimicrobials with Endotoxin Neutralizing and Anti-Inflammatory Capabilities.

The therapeutic application of antimicrobial peptides (AMPs), a potential type of peptide-based biomaterial, is impeded by their poor antimicrobial activity and potential cytotoxicity as a lack of understanding of their structure-activity relationships. In order to comprehensively enhance the antibacterial and clinical application potency of AMPs, a rational approach was applied to design amphiphilic peptides, including head-to-tail cyclic, linear and D-proline antimicrobial peptides using the template (IR)nP(IR)nP (n = 1, 2 and 3). Results showed that these amphiphilic peptides demonstrated antimicrobial activity in a size-dependent manner and that cyclic peptide OIR3, which contained three repeating units (IR)3, had greater antimicrobial potency and cell selectivity than liner peptide IR3, DIR3 with D-Pro and gramicidin S (GS). Surface plasmon resonance and endotoxin neutralization assays indicated that OIR3 had significant endotoxin neutralization capabilities, which suggested that the effects of OIR3 were mediated by binding to lipopolysaccharides (LPS). Using fluorescence spectrometry and electron microscopy, we found that OIR3 strongly promoted membrane disruption and thereby induced cell lysis. In addition, an LPS-induced inflammation assay showed that OIR3 inhibited the pro-inflammatory factor TNF-α in RAW264.7 cells. OIR3 was able to reduce oxazolone-induced skin inflammation in allergic dermatitis mouse model via the inhibition of TNF-α, IL-1ß and IL-6 mRNA expression. Collectively, the engineered head-to-tail cyclic peptide OIR3 was considerable potential candidate for use as a clinical therapeutic for the treatment of bacterial infections and skin inflammation.

Short-term effects of meteorological factors on pediatric hand, foot, and mouth disease in Guangdong, China: a multi-city time-series analysis.

BACKGROUND: Literature shows inconsistency in meteorological effects on Hand, foot, and mouth disease (HFMD) in different cities. This multi-city study aims to investigate the meteorological effects on pediatric HFMD occurrences and the potential effect modification by geographic factors. METHODS: Based on daily time-series data in eight major cities in Guangdong, China during 2009-2013, mixed generalized additive models were employed to estimate city-specific meteorological effects on pediatric HFMD. Then, a random-effect multivariate meta-analysis was conducted to obtain the pooled risks and to explore heterogeneity explained by city-level factors. RESULTS: There were a total of 400,408 pediatric HFMD cases (children aged 0-14 years old) with an annual incidence rate of 16.6 cases per 1,000 children, clustered in males and children under 3 years old. Daily average temperature was positively associated with pediatric HFMD cases with the highest pooled relative risk (RR) of 1.52 (95 % CI: 1.30-1.77) at the 95th percentile of temperature (30.5 °C) as compared to the median temperature (23.5 °C). Significant non-linear positive effects of high relative humidity were also observed with a 13 % increase (RR = 1.13, 95 % CI: 1.00-1.28) in the risk of HFMD at the 99th percentile of relative humidity (86.9 %) as compared to the median value (78 %). The effect estimates showed geographic variations among the cities which was significantly associated with city's latitude and longitude with an explained heterogeneity of 32 %. CONCLUSIONS: Daily average temperature and relative humidity had non-linear and delayed effects on pediatric HFMD and the effects varied across different cities. These findings provide important evidence for comprehensive understanding of the climatic effects on pediatric HFMD and for the authority to take targeted interventions and measures to control the occurrence and transmission of HFMD.

A disposable immunosensor array using cellulose paper assembled chemiresistive biosensor for simultaneous monitoring of mycotoxins AFB1 and FB1.

Due to the common contamination of multiple mycotoxins in food, which results in stronger toxicity, it is particularly important to simultaneously test for various mycotoxins for the protection of human health. In this study, a disposable immunosensor array with low-cost was designed and fabricated using cellulose paper, polydimethylsiloxane (PDMS), and semiconducting single-walled carbon nanotubes (s-SWCNTs), which was modified with specific antibodies for mycotoxins AFB1 and FB1 detection. The strategy for fabricating the immunosensor array with two individual channels involved a two-step protocol starting with the form of two kinds of carbon films by depositing single-wall carbon nanotubes (SWCNTs) and s-SWCNTs on the cellulose paper as the conductive wire and sensing element, followed by the assembly of chemiresistive biosensor with SWCNTs strip as the wire and s-SWCNTs as the sensing element. After immobilizing AFB1-bovine serum albumin (AFB1-BSA) and FB1-bovine serum albumin (FB1-BSA) separately on the different sensing regions, the formation of mycotoxin-BSA-antibody immunocomplexes transfers to electrochemical signal, which would change with the different concentrations of free mycotoxins. Under optimal conditions, the immunosensor array achieved a limit of detection (LOD) of 0.46 pg/mL for AFB1 and 0.34 pg/mL for FB1 within a wide dynamic range from 1 pg/mL to 20 ng/mL. Furthermore, the AFB1 and FB1 spiked in the ground corn and wheat extracts were detected with satisfactory recoveries, demonstrating the excellent practicality of this established method for simultaneous detection of mycotoxins.

Biomineralized nanosilica-based organelles endow living yeast cells with non-inherent biological functions.

We propose a biomimetic strategy to construct engineered yeast cells (EYCs) by building intracellular silica nanoscaffolds as biomimetic organelles. These nanosilica-based organelles can coordinate with loaded drug and yeast as a shell could prevent drug leakage. In vivo results show that EYCs serve as a dually responsive drug delivery system, targeted with extracellular caps (folate) and triggered by intracellular SiO2 at the low pH of cancer tissue.

Quantifying the risk of hand, foot, and mouth disease (HFMD) attributable to meteorological factors in East China: A time series modelling study.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a widespread infectious disease in China. Associated meteorological factors have been widely studied, but their attributable risks have not been well quantified. OBJECTIVES: The study aimed to quantify the HFMD burden attributable to temperature and other meteorological factors. METHODS: The daily counts of HFMD and meteorological factors in all 574 counties of East China were obtained for the period from 2009 to 2015. The exposure-lag-response relationships between meteorological factors and HFMD were quantified by using a distributed lag non-linear model for each county and the estimates from all the counties were then pooled using a multivariate mete-regression model. Attributable risks were estimated for meteorological variables according to the exposure-lag-response relationships obtained before. RESULTS: The study included 4,058,702 HFMD cases. Non-optimal values of meteorological factors were attributable to approximately one third of all HFMD cases, and the attributable numbers of non-optimal ambient temperature, relative humidity, wind speed and sunshine hours were 815,942 (95% CI: 796,361-835,888), 291,759 (95% CI: 226,183-358,494), 92,060 (95% CI: 59,655-124,738) and 62,948 (95% CI: 20,621-105,773), respectively. The exposure-response relationship between temperature and HFMD was non-linear with an approximate "M" shape. High temperature had a greater influence on HFMD than low temperature did. There was a geographical heterogeneity related to water body, and more cases occurred in days with moderate high and low temperatures than in days with extreme temperature. The effects of meteorological factors on HFMD were generally consistent across subgroups. CONCLUSIONS: Non-optimal temperature is the leading risk factor of HFMD in East China, and moderate hot and moderate cold days had the highest risk. Developing subgroup-targeted and region-specific programs may minimize the adverse consequences of non-optimum weather on HFMD risk.

In situ generation of biocompatible amorphous calcium carbonate onto cell membrane to block membrane transport protein - A new strategy for cancer therapy via mimicking abnormal mineralization.

Herein, our aim is to develop a drug-free method without obvious side effects to treat cancer through biomineralization of biocompatible inorganic nanomaterials targeting onto cells' membrane to block transport proteins. We selected chondroitin sulfate as optimal target agent and linker to induce the in situ biomineralization of exogenous Ca2+ and CO32- at safe concentration to generate biocompatible calcium carbonate (CaCO3) nanostructures targeting onto cancer cells' membrane. The in vitro and in vivo assays indicated that the generated CaCO3 nanostructures could significantly inhibit the proliferation of cancer cells. Mechanism studies demonstrated that the mineralized CaCO3 nanostructures could bind with 66 membrane proteins. Deeply research revealed that the CaCO3 nanostructures could mainly block transport proteins, e.g. sodium/potassium-transporting ATPase, leading to the collapse of the mitochondrial membrane potential and the increase of the lactate dehydrogenase release into medium, and finally modulated cell cycle and induced the apoptosis of cancer cells. Our results may introduce promising possibilities for efficient and specific cancer treatment by producing biocompatible nanomaterials to block transport proteins.

Prenatal exposure to perfluoroalkyl substances is associated with lower hand, foot and mouth disease viruses antibody response in infancy: Findings from the Guangzhou Birth Cohort Study.

BACKGROUND: Perfluoroalkyl substances (PFASs) are synthetic chemicals widely used in industry and for commercial products. Their immunomodulatory effects are a growing health concern in children. Hand, Foot and Mouth Disease (HFMD) is a common childhood viral infection, and increased incidence of which has parallel the rise in PFAS exposure in the Asia-Pacific region. OBJECTIVE: We conducted the first study to assess whether prenatal exposure to PFAS was associated with a reduction in HFMD virus antibodies in infants. METHODS: We enrolled 201 mother-infant pairs from the Guangzhou Birth Cohort Study from July to October 2013. High performance liquid chromatography-mass spectrometry was employed to determine concentrations of specific PFAS isomers in cord blood. Neutralizing antibodies titers were measured against two HFMD viruses, enterovirus 71 (EV71) and coxsackievirus A 16 (CA16), in cord blood serum and blood serum at three months of age. RESULTS: Higher umbilical cord blood PFAS concentrations were associated with lower EV71 and CA16 antibody concentrations. A doubling in the composite sum of cord blood PFASs in three month old infants was associated with significant increase in the risk of HFMD antibody concentration below clinical protection level (≥1:8 titers) for CA16 (odds ratio, OR: 2.74 [95% confidence interval (CI): 1.33, 5.61] and for EV71 (OR = 4.55, 95% CI: 1.45, 4.28). This association was higher in boys at three months of age for CA16. CONCLUSIONS: Our findings suggest that cord blood PFAS exposure is associated with lower HFMD antibody in infancy. Given the widespread nature of PFAS exposures and the high global incidence of HFMD globally, these findings have substantial public health implications and therefore, these associations need to be replicated in a larger study to more definitively address the risk.

Modeling the Present and Future Incidence of Pediatric Hand, Foot, and Mouth Disease Associated with Ambient Temperature in Mainland China.

BACKGROUND: There is limited evidence about the association between ambient temperature and the incidence of pediatric hand, foot, and mouth disease (HFMD) nationwide in China. OBJECTIVES: We examined the childhood temperature-HFMD associations across mainland China, and we projected the change in HFMD cases due to projected temperature change by the 2090s. METHODS: Data on daily HFMD (children 0-14 y old) counts and weather were collected from 362 sites during 2009-2014. Daily temperature by the 2090s was downscaled under the Representative Concentration Pathway (RCP) 4.5 and 8.5 scenarios. Temperature-HFMD associations were quantified using a two-stage Poisson regression with a distributed lag nonlinear model. The impact of changes in temperature on the incidence of HFMD was estimated by combining the fitted temperature-HFMD associations with projected temperatures under each scenario, assuming a constant population structure. Sensitivity analyses were performed to assess the influence of primary model assumptions. RESULTS: During 2009-2014, >11 million HFMD cases were reported. In most regions, the temperature-HFMD association had an inverted U shape with a peak at approximately 20°C, but the association leveled off or continued to increase in the Inner Mongolia and Northeast regions. When estimates were pooled across all regions and the population size was held constant, the projected incidence of HFMD increased by 3.2% [95% empirical confidence interval (eCI): −13.5%, 20.0%] and 5.3% (95% eCI: −33.3%, 44.0%) by the 2090s under the RCP 4.5 and 8.5 scenarios, respectively. However, regional projections suggest that HFMD may decrease with climate change in temperate areas of central and eastern China. CONCLUSION: Our estimates suggest that the association between temperature and HFMD varies across China and that the future impact of climate change on HFMD incidence will vary as well. Other factors, including changes in the size of the population at risk (children 0-14 y old) will also influence future HFMD trends. https://doi.org/10.1289/EHP3062.

Osteoblast response to the surface topography of hydroxyapatite two-dimensional films.

In the current study, three hydroxyapatite two-dimensional films with similar wettability but different topological roughness have been prepared through a facile one-step method using hydrated polylactic acid discs as substrates. The results indicated that the protein adsorption capabilities of the hydroxyapatite two-dimensional films and the proliferation of osteoblast cells on the as-prepared films increased obviously with the increase of the films' roughness. These reveal that the cellular responses to two-dimensional materials can be efficiently tuned by easily adjusting the topological roughness. This finding affords an efficient strategy to regulate the cellular response to bioinorganic two-dimensional materials and significantly expanded their application potentials in tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 991-999, 2017.

Assessment of temperature effect on childhood hand, foot and mouth disease incidence (0-5years) and associated effect modifiers: A 17 cities study in Shandong Province, China, 2007-2012.

BACKGROUND: Previous studies examining temperature-disease associations of hand, foot and mouth disease (HFMD) mainly focused on a single city. The results demonstrated great heterogeneity. A multi-city study is necessary to better understand temperature risk on the childhood incidence of HFMD and the associated modified factors. OBJECTIVE: To assess the effect of ambient temperature on childhood HFMD incidence and explore the potential associated effect modifiers in the study area. METHODS: Daily morbidity data and meteorological variables of the 17 cities were collected for the period from 2007 to 2012. Distributed lag non-linear model (DLNM) was used to estimate city-specific effects of temperature on HFMD incidence. A multivariate meta-analysis was then applied to pool the estimated city-specific effect. Potential effect modifiers were included in the multivariate meta-regression as meta-predictors. RESULTS: A total of 504,017 childhood HFMD cases were included in the study. The high-incidence period of HFMD was detected in late spring and early summer (April to June). The temperature-disease associations of the 17 cities demonstrated great heterogeneity and the pooled exposure-response curve was an approximately inverted V-shape. Regional indicator, numbers of healthcare institution and annual household income were considered as associated modifiers. CONCLUSION: Our findings can provide a practical reference for the early warning and intervention strategies of HFMD. Different temperature-disease associations among different regions should be considered when formulating and optimizing public health policy.

Additive-free fabrication of spherical hollow palladium/copper alloyed nanostructures for fuel cell application.

Herein, through tuning the surface energy difference of the major crystal planes by alloying, hollow palladium/copper alloyed nanostructures are successfully prepared through a one-pot template-free strategy. Compared with the solid PdCu alloyed nanoparticles, the hollow PdCu alloyed nanostructures exhibit the increased accessible electrochemical active surface area and the enhanced electrocatalytic activity for formic acid oxidation. It is concluded that the as-prepared hollow PdCu alloyed nanostructures would be a potential candidate as an anode electrocatalyst in direct formic acid fuel cell. More importantly, the strategy developed in this study might be expanded to fabricate other metal alloyed hollow nanostructures.