Particle Design and Inhalation Delivery of Iodine for Upper Respiratory Tract Infection Therapy.

Diseases caused by upper respiratory tract (URT) and pulmonary infections have been a serious threat to human health for millennia and lack of targeted effective therapeutic techniques. In this study, two kinds of cyclodextrin particles with typical particle shapes of nanocubes and microbars were synthesized through a facile process. Subsequently, the particles were used as carriers for loading and stabilizing iodine and characterizations were performed to demonstrate the loading mechanism. Next-generation impactor (NGI) experiments showed that iodine-loaded microbars (I2@microbars) had a deposition rate of 79.75% in URT, while iodine-loaded nanocubes (I2@nanocubes) were delivered to the deep lungs with a fine particle fraction (FPF) of 46.30%. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) indicated that the iodine-loaded nanocubes and microbars had similar bactericidal effect to povidone iodine solution. Cell viability studies and extracellular pro-inflammatory factor (TNF-α, IL-1ß, IL-6) evaluations demonstrate noncytotoxic effects of the blank carriers and anti-inflammatory effects of iodine-loaded samples. The irritation of the rat pharynx by I2@microbars was evaluated for the behavioral observations, body weight changes, histopathological studies, and TNF-α, IL-1ß, and IL-6 levels in pharyngeal tissues. The results showed that I2@microbars had no irritation to rat pharyngeal tissues at therapeutic doses. In conclusion, the present study provides novel treatment of URT infections via supramolecular cyclodextrin carriers for URT local therapy with iodine loading by a solvent-free method, which enhances the stability and reduces the inherent irritation without inhibiting their antimicrobial effects. Two kinds of cyclodextrin particles with typical shapes of microbars and nanocubes were synthesized by a facile process. Subsequently, iodine was successfully loaded into the particles by gas-solid interaction. The iodine-loaded microbars showed air dynamics characteristics for inhalation delivery to the upper respiratory tract with little alveolar deposition in the lungs.

Autism-associated neuroligin-3 deficiency in medial septum causes social deficits and sleep loss in mice.

Patients with autism spectrum disorder (ASD) frequently experience sleep disturbance. Genetic mutations in Neuroligin-3 (NLG3) genes are highly correlative with ASD and sleep disturbance. However, the cellular and neural circuit bases of this correlation remain elusive. Here, we find the conditional knockout of NLG3 (NLG3-CKO) in the medial septum (MS) impairs social memory and reduces sleep. NLG3 knockout in MS causes hyperactivity of MS-GABA neurons during social avoidance and wakefulness. Activation of MSGABA neurons induces social memory deficits and sleep loss in C57BL/6 mice. In contrast, inactivation of these neurons ameliorates social memory deficits and sleep loss in NLG3-CKO mice. Sleep deprivation leads to social memory deficits, while social isolation causes sleep loss, both resulting in a reduction of NLG3 expression and an increase in activity of GABAergic neurons in MS from C57BL/6 mice. Furthermore, MS-GABA-innervated CA2 neurons specifically regulate social memory without impacting sleep, whereas MSGABA-innervating neurons in the preoptic area selectively control sleep without affecting social behavior. Together, these findings demonstrate that the hyperactive MS-GABA neurons impair social memory and disrupt sleep resulting from NLG3 knockout in MS, and achieve the modality specificity through their divergent downstream targets.

Visualization of nasal powder distribution using biomimetic human nasal cavity model.

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Interactions of Muscovy duck reovirus, gut microbiota, and host innate immunity: Transcriptome and gut microbiota analysis.

It has been shown that Muscovy duck reovirus (MDRV) infection causes severe intestinal barrier damage and intestinal mucosal immune suppression. The health and balance of gut microbes is essential for the progression of intestinal infectious diseases. To investigate the interaction of MDRV, intestinal bacteria with host intestinal innate immunity, an MDRV contact-infection model was established in this study. High-throughput sequencing technology was used to sequence 16S rDNA and transcripts in ileal samples from experimental Muscovy ducklings. Our results suggest that intestinal opportunistic pathogens such as Streptococcus and Corynebacterium proliferated massively in MDRV-infected Muscovy ducklings. The body initiates antiviral and antibacterial immunity and actively fights the infection of gut microbes. The synthesis of peptidoglycan, lipopolysaccharide, and flagellin by intestinal bacteria activates the Toll-like receptor signaling pathway resulting in increased secretion of IFN-ß, IL-1ß, and IL-8. The RIG-I-like receptor signaling pathway is an important signaling pathway for the interaction between MDRV and the host. At the same time, we also observed that multiple genes in the JAK-STAT signaling pathway were significantly different. These genes are important targets for studying the immunosuppression caused by MDRV. In conclusion, we analyzed the interaction of MDRV, intestinal flora and host immune system during MDRV infection, which provides a basis for the further study on the mechanism of intestinal immunosuppression caused by MDRV.

Analysis of Nonlinear Transient Energy Effect on Thermoelectric Energy Storage Structure.

In complex flight conditions, due to the large amount of unusable heat generated by aerodynamic heating, the thermal protection system of an aircraft needs to withstand a large temperature shock, which brings great challenges to the design of the structure. In order to effectively utilize the irregular aerodynamic heat, and improve structural heat conduction, a composite structure is formed by using phase change energy storage materials on the basis of the thermoelectric structure, which transforms the aerodynamic waste heat into stable electric energy for the internal system. Through the study of the response of nonlinear transient energy, it is found that the thermoelectric and mechanical properties of the new structure can be improved by adding phase change energy storage materials. Under actual flight conditions, the new structure can reduce the maximum temperature by 180 K and the maximum thermal stress by 110 Mpa. The mechanical properties of the structure are effectively improved, the service life of the structure is prolonged, and the waste heat can be converted into stable electrical energy output to improve the thermoelectric output performance. On the premise of ensuring conversion efficiency, the output power of the new structure has been improved by 64.8% through structural optimization under actual flight conditions.

Molecularly imprinted electrochemical sensor based on Au nanoparticles in carboxylated multi-walled carbon nanotubes for sensitive determination of olaquindox in food and feedstuffs.

A novel molecularly imprinted electrochemical sensor (MIECS) was proposed to determine olaquindox (OLA) using gold nanoparticles in molecularly imprinted polymer (AuNPs@MIP) and carboxylated multi-walled carbon nanotubes (cMWCNTs). Glassy carbon electrode (GCE) was modified with cMWCNTs (cMWCNTs/GCE), and AuNPs/cMWCNT/GCE was obtained by electrodeposition on cMWCNTs/GCE using chronoamperometry in HAuCl4. Then, the obtained MIP/AuNPs/cMWCNTs/GCE was electropolymerized using OLA as template and o-PD as monomer to determine OLA. Important experimental parameters, namely, scan cycles, mole ratio of template molecules to functional monomers, pH value, and incubation time were optimized. The novel MIP sensor can offer a 2.7nM of detection limit for OLA. In addition, a series of food and feedstuffs were analyzed to demonstrate the feasibility of MIECS.