Repeated exposure to heterologous hepatitis C viruses associates with enhanced neutralizing antibody breadth and potency

A prophylactic hepatitis C virus (HCV) vaccine that elicits neutralizing antibodies could be key to HCV eradication. However, the genetic and antigenic properties of HCV envelope (E1E2) proteins capable of inducing anti-HCV broadly neutralizing antibodies (bNAbs) in humans have not been defined. Here, we investigated the development of bNAbs in longitudinal plasma of HCV-infected persons with persistent infection or spontaneous clearance of multiple reinfections. By measuring plasma antibody neutralization of a heterologous virus panel, we found that the breadth and potency of the antibody response increased upon exposure to multiple genetically distinct infections and with longer duration of viremia. Greater genetic divergence between infecting strains was not associated with enhanced neutralizing breadth. Rather, repeated exposure to antigenically related, antibody-sensitive E1E2s was associated with potent bNAb induction. These data reveal that a prime-boost vaccine strategy with genetically distinct, antibody-sensitive viruses is a promising approach to inducing potent bNAbs in humans.     

Evaluation of multifunctional synthetic tetralone derivatives for treatment of Alzheimer's disease

Neurodegeneration, a complex disease state, comprises several pathways that contribute to cell death. Conventional approach of targeting only one of these pathways has not been proven to be entirely successful and has demanded a hypothetical change as to how researchers design and develop new drugs. In this study, effects of a series of α, β‐unsaturated carbonyl‐based tetralone derivatives against Alzheimer's disease (AD) were investigated. Moreover, their activity toward amyloid β‐induced cytotoxicity was also studied. Six compounds including 3f , 3o , 3u , 3ae , 3af , and 3ag were discovered to be most protective against Aβ‐induced neuronal cell death in PC12 cells. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against MAO‐B, AChE, and self‐induced Aβ_1–42 aggregation. The compound 3f exhibited best AChE (IC₅₀ = 0.045 ± 0.02 μm ) inhibitory potential in addition to potent inhibition of MAO‐B (IC₅₀ = 0.88 ± 0.12 μm ). Furthermore, compound 3f disassembled the Aβ fibrils produced by self‐induced Aβ aggregation by 78.2 ± 4.8%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment.     

Iron oxide nanoparticles supported on biogenic silica derived from bamboo leaf ash for rhodamine B photodegradation

This research demonstrates the use of biogenic silica derived from bamboo leaf ash as a support for iron oxide nanoparticles. The preparation includes silica extraction from bamboo leaf ash and iron oxide nanoparticle impregnation into the silica gel under hydrothermal conditions, which is followed by calcination at 400 °C for 2 h. The physicochemical characterization includes X-ray diffraction analysis, gas sorption analysis, scanning electron microscopic analysis and transmission electron microscopic analysis. The light absorption capability and the band gap energy of the materials were determined by diffuse-reflectance UV–visible spectrophotometry. The materials obtained by varying the Fe content to 5 and 10% wt. were evaluated in rhodamine B photocatalytic degradation and photooxidation systems. It was found that the materials have a combined hematite and magnetite nanostructure, with the ratio of 9:10, and the particle sizes range from 10 to 40 nm. With a band gap energy of 2.27 eV, the prepared materials produce the successive photocatalytic degradation of rhodamine B. It was clarified that the formation of composite enhances stability and reusability of photocatalyst as shown by the stable initial rate at wide pH range and reuse for 5 cycles. Degradation mechanism is enhanced by the addition of H₂O₂ as an oxidant, and the investigation of the effect of scavengers shows that the degradation rate not only depends on radical formation but also on other species related to the formation of oxidizing agent.     

Evaluation of Moisture Damage Potential in Hot Mix Asphalt Using Polymeric Aggregate Treatment

To enhance the moisture damage performance of hot mix asphalt (HMA), treating the aggregate surface with a suitable additive was a more convenient approach. In this research, two types of aggregate modifiers were used to study the effect of moisture damage on HMA. Three different aggregate sources were selected based on their abundance of use in HMA. To study the impact of these aggregate modifiers on moisture susceptibility of HMA, the indirect tensile strength test and indirect tensile modulus test were used as the performance tests. Moisture conditioning of specimens was carried out to simulate the effect of moisture on HMA. The prepared samples’ tensile strength ratio (TSR) and stiffness modulus (Sm) results indicated a decrease in the strength of the HMA after moisture conditioning. After treating the aggregate surface with additives, an improvement was seen in dry and wet strength and stiffness. Moreover, an increasing trend was observed for both additives. The correlation between TSR and strength loss reveals a strong correlation (R² = 0.7219). Also, the two additives indicate increased wettability of asphalt binder over aggregate, thus improving the adhesion between aggregate and asphalt binder.     

Predicting Compressive and Splitting Tensile Strengths of Silica Fume Concrete Using M5P Model Tree Algorithm

Compressive strength (CS) and splitting tensile strength (STS) are paramount parameters in the design of reinforced concrete structures and are required by pertinent standard provisions. Robust prediction models for these properties can save time and cost by reducing the number of laboratory trial batches and experiments needed to generate suitable design data. Silica fume (SF) is often used in concrete owing to its substantial enhancements of the engineering properties of concrete and its environmental benefits. In the present study, the M5P model tree algorithm was used to develop models for the prediction of the CS and STS of concrete incorporating SF. Accordingly, large databases comprising 796 data points for CS and 156 data records for STS were compiled from peer-reviewed published literature. The predictions of the M5P models were compared with linear regression analysis and gene expression programming. Different statistical metrics, including the coefficient of determination, correlation coefficient, root mean squared error, mean absolute error, relative squared error, and discrepancy ratio, were deployed to appraise the performance of the developed models. Moreover, parametric analysis was carried out to investigate the influence of different input parameters, such as the SF content, water-to-binder ratio, and age of the specimen, on the CS and STS. The trained models offer a rapid and accurate tool that can assist the designer in the effective proportioning of silica fume concrete.     

Perinatal asphyxia in infants of insulin-dependent diabetic mothers

Infants of diabetic mothers are thought to be at risk for perinatal asphyxia. We hypothesized that the following are significant risk factors for perinatal asphyxia: poor third-trimester glycemic control, diabetic vascular disease (nephropathy, retinopathy) appearing in pregnancy, pregnancy-associated hypertension, smoking, prematurity, fetal macrosomia, and maternal hyperglycemia and hypoglycemia within 6 hours preceding delivery. We prospectively studied 162 infants born to 149 diabetic mothers (White classes B through R-T). Perinatal asphyxia was defined clinically as fetal distress during labor (late decelerations, persistent fetal bradycardia, or both), 1-minute Apgar score less than or equal to 6, or intrauterine fetal death. Forty-four infants (26.7%) had perinatal asphyxia. The presence of perinatal asphyxia did not correlate with third-trimester glycemic control, pregnancy-associated hypertension, smoking, fetal macrosomia, or maternal hypoglycemia before delivery, but it did correlate significantly with nephropathy appearing in pregnancy, maternal hyperglycemia before delivery, and prematurity. We speculate that (1) the appearance of diabetic vasculopathy (nephropathy) during pregnancy is accompanied by placental vascular disease and subsequently by fetal compromise and (2) in pregnancy complicated by diabetes, maternal and subsequently fetal hyperglycemia before delivery leads to fetal hypoxemia.     

Acute toxicity of hexavalent chromium in isolated teleost hepatocytes

Acute toxic effects of hexavalent chromium [Cr(VI)], a widely recognised carcinogenic, mutagenic and redox active metal, were investigated in isolated hepatocytes of goldfish (Carassius auratus). Exposure to 250 microM Cr(VI) induced a significant decrease of cell viability from 94% in controls to 88% and 84% after 30 min and 4 h of exposure, respectively. Cr-toxicity was associated with a concentration-dependent stimulation of the formation of reactive oxygen species (ROS). As one potential source of ROS formation we identified the lysosomal Fe(2+) pool, since the ferric ion chelator deferoxamin inhibited ROS formation by approximately 15%. Lysosomal membranes remained nevertheless intact during Cr-exposure, as determined from neutral red retention in this compartment. Another significant source of ROS appear to be the mitochondria, where a presumably uncoupled increase of respiration by 20-30% was triggered by the metal. Inhibition of mitochondrial respiration by cyanide caused an approximately 40% decrease of Cr-induced ROS-formation, whereas the uncoupling agent carbonyl cyanide m-chlorophenyl hydrazine was without effect. Cellular Ca(2+) homeostasis was not disturbed by Cr(VI) and thus played no role in this scenario. Overall, our data show that Cr(VI) is acutely toxic to goldfish hepatocytes, and its toxicity is associated with the induction of radical stress, presumably involving lysosomes and mitochondria as important sources of ROS formation.     

A-site deficient semiconductor electrolyte Sr1−xCoxFeO3−δ for low-temperature (450–550 °C) solid oxide fuel cells

Fast ionic conduction at low operating temperatures is a key factor for the high electrochemical performance of solid oxide fuel cells (SOFCs). Here an A-site deficient semiconductor electrolyte Sr_1−xCo_xFeO_3−δ is proposed for low-temperature solid oxide fuel cells (LT-SOFCs). A fuel cell with a structure of Ni/NCAL-Sr_0.7Co_0.3FeO_3−δ–NCAL/Ni reached a promising performance of 771 mW cm⁻² at 550 °C. Moreover, appropriate doping of cobalt at the A-site resulted in enhanced charge carrier transportation yielding an ionic conductivity of >0.1 S cm⁻¹ at 550 °C. A high OCV of 1.05 V confirmed that neither short-circuiting nor power loss occurred during the operation of the prepared SOFC device. A modified composition of Sr_0.5Co_0.5FeO_3−δ and Sr_0.3Co_0.7FeO_3−δ also reached good fuel cell performance of 542 and 345 mW cm⁻², respectively. The energy bandgap analysis confirmed optimal cobalt doping into the A-site of the prepared perovskite structure improved the charge transportation effect. Moreover, XPS spectra showed how the Co-doping into the A-site enhanced O-vacancies, which improve the transport of oxide ions. The present work shows that Sr_0.7Co_0.3FeO_3−δ is a promising electrolyte for LT-SOFCs. Its performance can be boosted with Co-doping to tune the energy band structure.

Fast ionic conduction at low operating temperatures is a key factor for the high electrochemical performance of solid oxide fuel cells (SOFCs).     

Effects of DDT on Amyloid Precursor Protein Levels and Amyloid Beta Pathology: Mechanistic Links to Alzheimer’s Disease Risk

Background: The interaction of aging-related, genetic, and environmental factors is thought to contribute to the etiology of late-onset, sporadic Alzheimer’s disease (AD). We previously reported that serum levels of p,p′-dichlorodiphenyldichloroethylene (DDE), a long-lasting metabolite of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT), were significantly elevated in patients with AD and associated with the risk of AD diagnosis. However, the mechanism by which DDT may contribute to AD pathogenesis is unknown.Objectives: This study sought to assess effects of DDT exposure on the amyloid pathway in multiple in vitro and in vivo models.Methods: Cultured cells (SH-SY5Y and primary neurons), transgenic flies overexpressing amyloid beta (Aβ), and C57BL/6J and 3xTG-AD mice were treated with DDT to assess impacts on the amyloid pathway. Real time quantitative polymerase chain reaction, multiplex assay, western immunoblotting and immunohistochemical methods were used to assess the effects of DDT on amyloid precursor protein (APP) and other contributors to amyloid processing and deposition.Results: Exposure to DDT revealed significantly higher APP mRNA and protein levels in immortalized and primary neurons, as well as in wild-type and AD-models. This was accompanied by higher levels of secreted Aβ in SH-SY5Y cells, an effect abolished by the sodium channel antagonist tetrodotoxin. Transgenic flies and 3xTG-AD mice had more Aβ pathology following DDT exposure. Furthermore, loss of the synaptic markers synaptophysin and PSD95 were observed in the cortex of the brains of 3xTG-AD mice.Discussion: Sporadic Alzheimer’s disease risk involves contributions from genetic and environmental factors. Here, we used multiple model systems, including primary neurons, transgenic flies, and mice to demonstrate the effects of DDT on APP and its pathological product Aβ. These data, combined with our previous epidemiological findings, provide a mechanistic framework by which DDT exposure may contribute to increased risk of AD by impacting the amyloid pathway. https://doi.org/10.1289/{"type":"entrez-protein","attrs":{"text":"EHP10576","term_id":"372009961","term_text":"EHP10576"}}EHP10576     

Influence of Tantalum Addition on the Corrosion Passivation of Titanium-Zirconium Alloy in Simulated Body Fluid

Ti-15%Zr alloy and Ti-15%Zr-2%Ta alloy were fabricated to be used in biomedical applications. The corrosion of these two alloys after being immersed in simulated body fluid for 1 h and 72 h was investigated. Different electrochemical methods, including polarization, impedance, and chronoamperometric current with time at 400 mV were employed. Also, the surface morphology and the compositions of its formed film were reported by the use of scanning electron microscope and energy dispersive X-ray. Based on the collected results, the presence of 2%Ta in the Ti-Zr alloy passivated its corrosion by minimizing its corrosion rate. The polarization curves revealed that adding Ta within the alloy increases the corrosion resistance as was confirmed by the impedance spectroscopy and current time data. The change of current versus time proved that the addition of Ta reduces the absolute current even at high anodic potential, 400 mV. The results of both electrochemical and spectroscopic methods indicated that pitting corrosion does not occur for both Ti-Zr and Ti-Zr-Ta alloys, even after their immersion in SBF solutions for 72 h.