Polyclonal but not monoclonal circulating memory CD4+ T cells attenuate the severity of Staphylococcus aureus bacteremia.

Staphylococcus aureus bacteremia causes significant morbidity and mortality. Treatment of staphylococcal infections is hindered by widespread antibiotic resistance, and attempts to develop an S. aureus vaccine have failed. Improved S. aureus treatment and infection prevention options require a deeper understanding of the correlates of protective immunity. CD4+ T cells have been identified as key orchestrators in the defense against S. aureus, but uncertainties persist regarding the subset, polarity, and breadth of the memory CD4+ T-cell pool required for protection. Here, using a mouse model of systemic S. aureus infection, we discovered that the breadth of bacterium-specific memory CD4+ T-cell pool is a critical factor for protective immunity against invasive S. aureus infections. Seeding mice with a monoclonal bacterium-specific circulating memory CD4+ T-cell population failed to protect against systemic S. aureus infection; however, the introduction of a polyclonal and polyfunctional memory CD4+ T-cell pool significantly reduced the bacterial burden. Our findings support the development of a multi-epitope T-cell-based S. aureus vaccine, as a strategy to mitigate the severity of S. aureus bacteremia.

Intranasal Epitope-Polymer Vaccine Lodges Resident Memory T Cells Protecting Against Influenza Virus.

Intranasal vaccines, unlike injectable vaccines, boost immunity along the respiratory tract; this can significantly limit respiratory virus replication and shedding. There remains a need to develop mucosal adjuvants and vaccine delivery systems that are both safe and effective following intranasal administration. Here, biopolymer particles (BP) densely coated with repeats of MHC class I restricted immunodominant epitopes derived from influenza A virus namely NP366, a nucleoprotein-derived epitope and PA224, a polymerase acidic subunit derived epitope, are bioengineered. These BP-NP366/PA224 can be manufactured at a high yield and are obtained at ≈93% purity, exhibiting ambient-temperature stability. Immunological characterization includes comparing systemic and mucosal immune responses mounted following intramuscular or intranasal immunization. Immunization with BP-NP366/PA224 without adjuvant triggers influenza-specific CD8+ T cell priming and memory CD8+ T cell development. Co-delivery with the adjuvant poly(I:C) significantly boosts the size and functionality of the influenza-specific pulmonary resident memory CD8+ T cell pool. Intranasal, but not intramuscular delivery of BP-NP366/PA224 with poly(I:C), provides protection against influenza virus challenge. Overall, the BP approach demonstrates as a suitable antigen formulation for intranasal delivery toward induction of systemic protective T cell responses against influenza virus.

Source, transport, and toxicity of emerging contaminants in aquatic environments: A review on recent studies.

Emerging contaminants (ECs) are gaining global attention owing to their widespread presence and adverse effects on human health. ECs comprise numerous composite types and pose a potential threat to the growth and functional traits of species and ecosystems. Although the occurrence and fate of ECs has been extensively studied, little is known about their long-term biological effects. This review attempts to gain insights into the unhindered connections and overlaps in aquatic ecosystems. Microplastics (MPs), one of the most representative ECs, are carriers of other pollutants because of their strong adsorption capacity. They form a complex of pollutants that can be transmitted to aquatic organisms and humans through the extended food chain, increasing the concentration of pollutants by tens of thousands of times. Adsorption, interaction and transport effects of emerging contaminants in the aquatic environment are also discussed. Furthermore, the current state of knowledge on the ecotoxicity of single- and two-pollutant models is presented. Herein, we discuss how aquatic organisms within complex food networks may be particularly vulnerable to harm from ECs in the presence of perturbations. This review provides an advanced understanding of the interactions and potential toxic effects of ECs on aquatic organisms.

Impact of ambient air pollution on physical activity and sedentary behavior in children.

BACKGROUND: Exposure to air pollution has become a serious environmental issue affecting children's health and health-related behavior in China. Previous studies have focused on the associations between air pollution and physical activity among adults; however, few have examined the relationship between air pollution and health-related behavior among children, which are particularly susceptible population subgroups. The present study aims to examine the impact of air pollution on daily physical activity (PA) and sedentary behavior (SB) among children in China. METHODS: PA and SB data were collected by actiGraph accelerometers for eight consecutive days. PA and SB data from 206 children were matched to daily air pollution obtained from the Ministry of Environmental Protection of the People's Republic of China, including the average daily air quality index (AQI), PM2.5 (µg/m³), and PM10 (µg/m³). Associations were estimated using linear individual fixed-effect regressions. RESULTS: A 10-unit increase in daily AQI was associated with a reduction in daily PA by 5.94 (95% confidence interval [CI] = -8.79, -3.08) minutes of moderate to vigorous physical activity (MVPA) and 229.82 (95% CI = -345.35, -114.28) walking steps and an increase in daily SB by 15.77 (95% CI = 9.01, 22.53) minutes. A 10 µg/m³ increase in air pollution concentration in daily PM2.5 was associated with a reduction in daily PA by 7.51 (95% CI = -11.04, -3.97) minutes of MVPA, 295.69 (95% CI = -438.46, -152.92) walking steps and an increase in daily SB by 21.12 (95% CI = 12.77, 29.47) minutes. A 10 µg/m³ increase in air pollution concentration in daily PM10 was associated with a reduction in daily PA by 13.18 (95% confidence interval [CI] = -15.98, -10.37) minutes of MVPA, 518.34 (95% CI = -631.77, -404.91) walking steps and an increase in daily SB by 19.87 (95% CI = 13.10, 26.64) minutes. CONCLUSION: Air pollution may discourage physical activity and increase sedentary behavior among children. Policy interventions are needed to reduce air pollution and develop strategies to decrease risks to children's health.

Global gene expression analysis in liver of db/db mice treated with catalpol.

Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg-1), and 10 db/m mice were used as the normal control. All the groups were administered orally for 8 weeks. The levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene expression in liver tissues were analyzed. Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of catalpol was better than that of metformin. Furthermore, catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity. Catalpol treatment significantly decreased GSP level. The comparisons of gene expression in liver tissues among normal control mice, db/db mice and catalpol treated mice (200 and 100 mg·kg-1) indicated that there were significant increases in the expressions of 287 genes, whichwere mainly involved in lipid metabolism, response to stress, energy metabolism, and cellular processes, and significant decreases in the expressions of 520 genes, which were mainly involved in cell growth, death, immune system, and response to stress. Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2 (isocitrate dehydrogenase 2 (NADP+), mitochondrial), G6pd2 (glucose-6-phosphate dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion, catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.

On chip chirality-distinguishing beamsplitter.

The chirality of photons plays a fundamental role in light-matter interactions. However, a limiting factor in photonic integrated circuits is the lack of a miniaturized component, which can distinguish the chirality in a low cost and integrated manner. Herein we numerically demonstrate a chirality-distinguishing beamsplitter that can address this challenge. It consists of an integrated polarization rotator and a linear polarization beamsplitter, which together can fulfill the task of distinguishing and splitting left- and right-handed quasi-circularly polarized modes on a chip with an ultra-broadband operation range from 1.45 µm to 1.65 µm. Owning to the reciprocity, the device can emit photons with selectable spin angular momentum depending on the chosen feeding waveguide. The device is compatible with complementary metal-oxide semiconductor technology and it may open up new avenues in the fields of on-chip nano-photonics, bio-photonics and quantum information science.

Carboxymethyl chitosan/phospholipid bilayer-capped mesoporous carbon nanoparticles with pH-responsive and prolonged release properties for oral delivery of the antitumor drug, Docetaxel.

In this article, a new type of carboxymethyl chitosan/phospholipid bilayer-capped mesoporous carbon nanomatrix (CCS/PL/MC) was fabricated as a potential nano-drug delivery system. In this drug delivery system, a mesoporous carbon nanomatrix (MC) acts as the support for loading drug molecules, a positively charged phospholipid (PL) layer works as the inner shell for prolonged drug release and a negatively charged carboxymethyl chitosan (CCS) layer serves as the outer shell for pH-responsive drug release. Docetaxel (DTX) was selected as a model drug. The drug-loaded CCS/PL/MC was synthesized via a combination approach of double emulsion/solvent evaporation followed by lyophilization. The drug-loaded nanoparticles were characterized for their particle size, structure, morphology, zeta (ζ)-potential, specific surface area, porosity, drug loading and solid state. In vitro drug release tests showed that the drug-loaded CCS/PL/MC nanoparticles possess a good pH-sensitivity and prolonged releasing ability with negligible release in gastric media and controlled release in intestinal media. Compared with MC and PL-capped MC, CCS/PL/MC had a greater mucoadhesiveness. Moreover, cellular uptake study indicated that CCS/PL/MC might improve intracellular drug delivery. These results suggest that this hybrid nanocarrier, combining the beneficial features of CCS, PL and MC, is a promising drug delivery system able to improve the oral absorption of antitumor drugs.

Optical gears in a nanophotonic directional coupler.

Gears are rotating machines, meshing with each other by teeth to transmit torque. Interestingly, the rotating directions of two meshing gears are opposite, clockwise and counterclockwise. Although this opposite handedness motion has been widely investigated in machinery science, the analogue behavior of light remains undiscovered. Here, we present a simple nanophotonic directional coupler structure which can generate two light beams with opposite handedness of polarization states-optical gears. Due to the abrupt phase shift effect and birefringence effect, the angular momentum (AM) states of photons vary with the propagation distance in two adjacent waveguides of the coupler. Thus, by the choice of coupling length, it is able to obtain two light beams with opposite handedness of polarization, confirming the appearance of optical gears. The full control in the handedness of output beams is achieved via tuning the relative phase between two orthogonal modes at the input port. Optical gears thus offer the possibility of exploring light-matter interactions in nanoscale, opening up new avenues in fields of integrated quantum computing and nanoscale bio-sensing of chiral molecules.

Mitochondrial fusion/fission process involved in the improvement of catalpol on high glucose-induced hepatic mitochondrial dysfunction.

Catalpol, an iridoid glycoside, has been shown to exert hypoglycemic effect by rescuing mitochondrial function, but the detailed mechanism remains unclear yet. In this study, the effect and mechanism of catalpol on the hepatic mitochondria under diabetic conditions were further examined. Oral administration of catalpol significantly reduced the blood glucose, triglyceride, and cholesterol levels in high-fat diet- and streptozotocin-induced diabetic mice. Additionally, catalpol attenuated the decrease in liver mitochondrial ATP content resulting from diabetes. Furthermore, the number of mitochondria possessing a long size was increased in catalpol-treated mice. Interestingly, the catalpol-induced recovery of mitochondrial function was associated with decreased fission protein 1 and dynamin-related protein 1 expression as well as increased mitofusin 1 expression in the liver. In HepG2 cells, catalpol alleviated the decrease of ATP content and mitochondrial membrane potential, and the increase of reactive oxygen species formation induced by high glucose. MitoTracker Green stain shows that the tubular feature of mitochondria was maintained when cells were treated with catalpol. Catalpol also decreased fission protein 1 and dynamin-related protein 1 expression and increased mitofusin 1 expression in HepG2 cells. The present results suggest that catalpol can ameliorate hepatic mitochondrial dysfunction under a diabetic state, and this may be related to its regulation of mitochondrial fusion and fission events.

Biomass based activated carbon obtained from sludge and sugarcane bagasse for removing lead ion from wastewater.

Sewage sludge and bagasse were used as raw materials to produce cheap and efficient adsorbent with great adsorption capacity of Pb(2+). By pyrolysis at 800 °C for 0.5 h, the largest surface area (806.57 m(2)/g) of the adsorbent was obtained, enriched with organic functional groups. The optimal conditions for production of the adsorbent and adsorption of Pb(2+) were investigated. The results of adsorb-ability fitted the Langmuir isotherm and pseudo-second-order model well. The highest Pb(2+) (at pH = 4.0) adsorption capacity was achieved by treating with 60% (v/v) HNO3. This is a promising approach for metal removal from wastewater, as well as recycling sewage sludge and bagasse to ease their disposal pressure.

Development of novel mesoporous nanomatrix-supported lipid bilayers for oral sustained delivery of the water-insoluble drug, lovastatin.

The purpose of this study was to investigate the effect of a core/shell structured nanocomposite, mesoporous nanomatrix-supported lipid bilayer (MN-SLB), as an oral drug nanocarrier, on the dissolution behavior and in vivo absorption of a water-insoluble drug, lovastatin (LOV). The formulation strategy was based on the use of drug-loaded mesoporous silica as the core for the fusion of liposomes. Field emission scanning electron microscopy (FESEM), cryogenic transmission electron microscopy (Cryo-TEM) and nitrogen adsorption were used to systematically characterize the drug carrier and drug-loaded MN-SLB formulation, confirming the successful inclusion of LOV into the nano-pores of MN-SLB. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) confirmed that the incorporated drug in the carrier was in an amorphous state. An in vitro dissolution study showed that LOV-loaded MN-SLB exhibited a sustained drug release behavior. Compared with the LOV-loaded mesoporous silica particles, LOV-loaded MN-SLB markedly suppressed the burst release. Furthermore, the pharmacokinetics and relative bioavailability of the LOV-loaded MN-SLB formulation was studied in beagle dogs after oral administration and using a commercially available immediate release formulation (Sandoz Lovastatin®) as a reference. It was found that the relative bioavailability of LOV and LOV ß-hydroxy acid (LOVA) for the LOV-loaded MN-SLB formulation was 207.2% and 192.1%, respectively. In addition, MN-SLB exhibited negligible toxicity against Caco-2 and HT-29 cells in cytotoxicity assays. The results of this study indicate that the MN-SLB nanocomposite is a promising candidate as a novel oral drug delivery nanovehicle for controlling the dissolution rate and improving the oral absorption of water-insoluble drugs.

G5 PAMAM dendrimer versus liposome: a comparison study on the in vitro transepithelial transport and in vivo oral absorption of simvastatin.

This study compared formulation effects of a dendrimer and a liposome preparation on the water solubility, transepithelial transport, and oral bioavailability of simvastatin (SMV). Amine-terminated G5 PAMAM dendrimer (G5-NH2) was chosen to form SMV/G5-NH2 molecular complexes, and SMV-liposomes were prepared by using a thin film dispersion method. The effects of these preparations on the transepithelial transport were investigated in vitro using Caco-2 cell monolayers. Results indicated that the solubility and transepithelial transport of SMV were significantly improved by both formulations. Pharmacokinetic studies in rats also revealed that both the SMV/G5-NH2 molecular complexes and the SMV-liposomes significantly improved the oral bioavailability of SMV with the liposomes being more effective than the G5-NH2. The overall better oral absorption of SMV-liposomes as compared to SMV/G5-NH2 molecular complexes appeared to arise from better liposomal solubilization and encapsulation of SMV and more efficient intracellular SMV delivery. FROM THE CLINICAL EDITOR: Various carrier systems have been designed to enhance drug delivery via the oral route. In this study, the authors compared G5 PAMAM dendrimers to liposome preparations in terms of solubility, transepithelial transport, and oral bioavailability of this poorly water-soluble drug. This understanding has improved our knowledge in the further development of drug carrier systems.