Bioavailability, distribution and clearance of tracheally-instilled and gavaged uncoated or silica-coated zinc oxide nanoparticles

Background: Nanoparticle pharmacokinetics and biological effects are influenced by several factors. We assessed the effects of amorphous SiO2 coating on the pharmacokinetics of zinc oxide nanoparticles (ZnO NPs) following intratracheal (IT) instillation and gavage in rats. Methods: Uncoated and SiO2-coated ZnO NPs were neutron-activated and IT-instilled at 1 mg/kg or gavaged at 5 mg/kg. Rats were followed over 28 days post-IT, and over 7 days post-gavage. Tissue samples were analyzed for 65Zn radioactivity. Pulmonary responses to instilled NPs were also evaluated at 24 hours. Results: SiO2-coated ZnO elicited significantly higher inflammatory responses than uncoated NPs. Pulmonary clearance of both 65ZnO NPs was biphasic with a rapid initial t1/2 (0.2 - 0.3 hours), and a slower terminal t1/2 of 1.2 days (SiO2-coated ZnO) and 1.7 days (ZnO). Both NPs were almost completely cleared by day 7 (>98%). With IT-instilled 65ZnO NPs, significantly more 65Zn was found in skeletal muscle, liver, skin, kidneys, cecum and blood on day 2 in uncoated than SiO2-coated NPs. By 28 days, extrapulmonary levels of 65Zn from both NPs significantly decreased. However, 65Zn levels in skeletal muscle, skin and blood remained higher from uncoated NPs. Interestingly, 65Zn levels in bone marrow and thoracic lymph nodes were higher from coated 65ZnO NPs. More 65Zn was excreted in the urine from rats instilled with SiO2-coated 65ZnO NPs. After 7 days post-gavage, only 7.4% (uncoated) and 6.7% (coated) of 65Zn dose were measured in all tissues combined. As with instilled NPs, after gavage significantly more 65Zn was measured in skeletal muscle from uncoated NPs and less in thoracic lymph nodes. More 65Zn was excreted in the urine and feces with coated than uncoated 65ZnO NPs. However, over 95% of the total dose of both NPs was eliminated in the feces by day 7. Conclusions: Although SiO2-coated ZnO NPs were more inflammogenic, the overall lung clearance rate was not affected. However, SiO2 coating altered the tissue distribution of 65Zn in some extrapulmonary tissues. For both IT instillation and gavage administration, SiO2 coating enhanced transport of 65Zn to thoracic lymph nodes and decreased transport to the skeletal muscle

On Horava-Lifshitz "Black Holes"

The most general spherically symmetric solution with zero shift is found in the non-projectable Horava-Lifshitz class of theories with general coupling constants. It contains as special cases, spherically symmetric solutions found by other authors earlier. It is found that the generic solution has conventional (AdS, dS or flat) asymptotics with a universal 1/r tail. There are several special cases where the asymptotics differ, including the detailed balance choice of couplings. The conventional thermodynamics of this general class of solutions is established by calculating the energy, temperature and entropy. Although several of the solutions have conventional horizons, for particles with ultra-luminal dispersion relations such solutions appear to be horizonless.Comment: Latex 41 pages, 5 figure

Assessment of α-Synuclein Secretion in Mouse and Human Brain Parenchyma

Genetic, biochemical, and animal model studies strongly suggest a central role for α-synuclein in the pathogenesis of Parkinson's disease. α-synuclein lacks a signal peptide sequence and has thus been considered a cytosolic protein. Recent data has suggested that the protein may be released from cells via a non-classical secretory pathway and may therefore exert paracrine effects in the extracellular environment. However, proof that α-synuclein is actually secreted into the brain extracellular space in vivo has not been obtained. We developed a novel highly sensitive ELISA in conjugation with an in vivo microdialysis technique to measure α-synuclein in brain interstitial fluid. We show for the first time that α-synuclein is readily detected in the interstitial fluid of both α-synuclein transgenic mice and human patients with traumatic brain injury. Our data suggest that α-synuclein is physiologically secreted by neurons in vivo. This interstitial fluid pool of the protein may have a role in the propagation of synuclein pathology and progression of Parkinson's disease

Probing the nature of black holes: Deep in the mHz gravitational-wave sky

Black holes are unique among astrophysical sources: they are the simplest macroscopic objects in the Universe, and they are extraordinary in terms of their ability to convert energy into electromagnetic and gravitational radiation. Our capacity to probe their nature is limited by the sensitivity of our detectors. The LIGO/Virgo interferometers are the gravitational-wave equivalent of Galileo’s telescope. The first few detections represent the beginning of a long journey of exploration. At the current pace of technological progress, it is reasonable to expect that the gravitational-wave detectors available in the 2035-2050s will be formidable tools to explore these fascinating objects in the cosmos, and space-based detectors with peak sensitivities in the mHz band represent one class of such tools. These detectors have a staggering discovery potential, and they will address fundamental open questions in physics and astronomy. Are astrophysical black holes adequately described by general relativity? Do we have empirical evidence for event horizons? Can black holes provide a glimpse into quantum gravity, or reveal a classical breakdown of Einstein’s gravity? How and when did black holes form, and how do they grow? Are there new long-range interactions or fields in our Universe, potentially related to dark matter and dark energy or a more fundamental description of gravitation? Precision tests of black hole spacetimes with mHz-band gravitational-wave detectors will probe general relativity and fundamental physics in previously inaccessible regimes, and allow us to address some of these fundamental issues in our current understanding of nature

Antiviral Activity of Silver, Copper Oxide and Zinc Oxide Nanoparticle Coatings against SARS-CoV-2

SARS-CoV-2 is responsible for several million deaths to date globally, and both fomite transmission from surfaces as well as airborne transmission from aerosols may be largely responsible for the spread of the virus. Here, nanoparticle coatings of three antimicrobial materials (Ag, CuO and ZnO) are deposited on both solid flat surfaces as well as porous filter media, and their activity against SARS-CoV-2 viability is compared with a viral plaque assay. These nanocoatings are manufactured by aerosol nanoparticle self-assembly during their flame synthesis. Nanosilver particles as a coating exhibit the strongest antiviral activity of the three studied nanomaterials, while copper oxide exhibits moderate activity, and zinc oxide does not appear to significantly reduce the virus infectivity. Thus, nanosilver and copper oxide show potential as antiviral coatings on solid surfaces and on filter media to minimize transmission and super-spreading events while also providing critical information for the current and any future pandemic mitigation efforts

Silica-coated phosphorescent nanoprobes for selective cell targeting and dynamic bioimaging of pathogen–host cell interactions

Fluorescence in vitro bioimaging suffers from photobleaching of organic dyes, thus, functional probes with superior photostability are urgently needed. Here, we address this challenge by developing novel silica-coated nanophosphors that may serve as superior luminescent nanoprobes compatible with conventional fluorescence microscopes. We specifically explore their suitability for dynamic in vitro bioimaging of interactions between bacterial pathogens and host cells, and further demonstrate the facile surface functionalization of the amorphous silica layer with antibodies for selective cell targeting.ISSN:1359-7345ISSN:1364-548