Safe and efficient delivery of blood-brain barrier (BBB)-impermeable cargos into the brain through intravenous injection remains a challenge. Here, we developed a previously unknown class of ...neurotransmitter-derived lipidoids (NT-lipidoids) as simple and effective carriers for enhanced brain delivery of several BBB-impermeable cargos. Doping the NT-lipidoids into BBB-impermeable lipid nanoparticles (LNPs) gave the LNPs the ability to cross the BBB. Using this brain delivery platform, we successfully delivered amphotericin B (AmB), antisense oligonucleotides (ASOs) against tau, and genome-editing fusion protein (-27)GFP-Cre recombinase into the mouse brain via systemic intravenous administration. We demonstrated that the NT-lipidoid formulation not only facilitates cargo crossing of the BBB, but also delivery of the cargo into neuronal cells for functional gene silencing or gene recombination. This class of brain delivery lipid formulations holds great potential in the treatment of central nervous system diseases or as a tool to study the brain function.
Display omitted
•Type I (electron transfer) PDT of C60 is significantly enhanced by gold nanoparticles.•C60@GNPs can be excited under near-infrared light, which has a high tissue ...penetration.•C60@GNPs with near-infrared light irradiation can obtain oxygen non-dependent of PDT.
Recently, fullerene (C60) has been widely used as a nano photosensitizer (PS) for tumor related photodynamic therapy (PDT). However, current PDT based on C60 is severely restricted by the visible light source (shallow tissue penetrating depth) and oxygen dependent (tumor hypoxia). Therefore, taking advantages of the surface plasmon resonance (SPR) effect of gold nanoparticles (GNPs) and “electronic sponge” property of C60, a C60 based hybrid nanostructured photosensitizer (C60@GNPs) with high light stability, near infrared light (NIR) excitation, and oxygen non-dependent properties was rational designed according to the mechanism of PDT. Compared with C60, after GNPs in-situ synthesis, the PDT mechanism of C60@GNPs changed from type II to type I, and the main product of PDT changed from singlet oxygen to hydroxyl radicals. Furthermore, C60@GNPs hybrid could efficiently generate hydroxyl radicals under NIR light excitation even in the hypoxia condition. These results suggest that C60@GNPs hybrid has a great potential for in vivo PDT applications.
Grass pollen subcutaneous immunotherapy (SCIT) is associated with induction of serum IgG4-associated inhibitory antibodies that prevent IgE-facilitated allergen binding to B cells.
We sought to ...determine whether SCIT induces nasal allergen-specific IgG4 antibodies with inhibitory activity that correlates closely with clinical response.
In a cross-sectional controlled study, nasal fluid and sera were collected during the grass pollen season from 10 SCIT-treated patients, 13 untreated allergic patients (with seasonal allergic rhinitis SAR), and 12 nonatopic control subjects. Nasal and serum IgE and IgG4 levels to Phleum pratense components were measured by using the Immuno Solid Allergen Chip microarray. Inhibitory activity was measured by IgE-facilitated allergen binding assay. IL-10+ regulatory B cells were quantified in peripheral blood by using flow cytometry.
Nasal and serum Phl p 1– and Phl p 5–specific IgE levels were increased in patients with SAR compared to nonatopic control subjects (all, P < .001) and SCIT-treated patients (nasal, P < .001; serum Phl p 5, P = .073). Nasal IgG4 levels were increased in the SCIT group compared to those in the SAR group (P < .001) during the pollen season compared to out of season. IgG-associated inhibitory activity in nasal fluid and serum was significantly increased in the SCIT group compared to that in the SAR (both, P < .01). The magnitude of the inhibitory activity was 93% (P < .001) in nasal fluid compared to 66% (P < .001) in serum and was reversed after depletion of IgG. Both nasal fluid (r = −0.69, P = .0005) and serum (r = −0.552, P = .0095) blocking activity correlated with global symptom improvement. IL-10+ regulatory B cells were increased in season compared to out of season in the SCIT group (P < .01).
For the first time, we show that nasal IgG4-associated inhibitory activity correlates closely with the clinical response to allergen immunotherapy in patients with allergic rhinitis with or without asthma.
Display omitted
Sand fly Phlebotomus chinensis is a principle vector for the visceral leishmaniasis (VL) in China with a wide geographic distribution. Jiuzhaigou, Sichuan is a mountain type endemic area of VL in ...China. Long term effective control efforts in the region have successfully reduced VL transmission. To assess the current status of the sand flies and their ecological aspects in the region, a survey was conducted in the summer of 2014 and 2015.
Sand fly specimens were collected by light traps in a village and blood sources were identified by PCR and sequencing of the mitochondrial cytochrome b gene.
In a rock cave, 65.2 %-79.8 % of collected sand flies were male. On a rabbit farm, 92.9 %-98.8 % of specimens were female. In pig pens, 61.1 % of specimens were female. Some females had visible blood residues. The feeding rate was 49.4 % from the pig pens, 12.3 % from the cave, and only 1.7 % from the rabbit farm. Pig, rabbit, chicken, dog, and human blood were detected in the fed specimens. Swine blood, present in all tested samples, was a preferred blood source, while chicken and dog blood were present in a third of the samples.
In Jiuzhaigou County, Sichuan Province of China, the considerable sandfly density and the peridomestic feeding behavior all increases the risk of VL transmission, and insecticide spraying in animal sheds could be exploited to reduce sand fly populations in human surroundings.
Meta-devices have gained significant attention and have been widely utilized in optical systems for focusing and imaging, owing to their lightweight, high-integration, and exceptional-flexibility ...capabilities. However, based on the assumption of local phase approximation, traditional design method neglect the local lattice coupling effect between adjacent meta-atoms, thus harming the practical performance of meta-devices. Using physics-driven or data-driven optimization algorithms can effectively solve the aforementioned problems. Nevertheless, both of the methods either involve considerable time costs or require a substantial amount of data sets. Here, we propose a physics-data-driven approach based "intelligent optimizer" that enables us to adaptively modify the sizes of the studied meta-atom according to the sizes of its surrounding ones. Such a scheme allows to mitigate the undesired local lattice coupling effect, and the proposed network model works well on thousands of datasets with a validation loss of 3*10-3. Experimental results show that the 1-mm-diameter metalens designed with the "intelligent optimizer" possesses a relative focusing efficiency of 93.4% (as compared to ideal focusing) and a Strehl ratio of 0.94. In contrast to the previous inverse design method, our method significantly boosts designing efficiency with five orders of magnitude reduction in time. Our design approach may sets a new paradigm for devising large-scale meta-devices.
PDF
