Mesoporous silica nanoparticles as smart and safe devices for regulating blood biomolecule levels

Stimuli-responsive end-capped MSN materials are promising drug carriers that securely deliver a large payload of drug molecules without degradation or premature release. A general review of the recent progress in this field is presented, including a summary of a series of hard and soft caps for drug encapsulation and a variety of internal and external stimuli for controlled release of different therapeutics, a discussion of the biocompatibility of MSN both in vitro and in vivo, and a description of the sophisticated stimuli-responsive systems with novel capping agents and controlled release mechanism. The unique internal and external surfaces of MSN were utilized for the development of a glucose-responsive double delivery system end-capped with insulin. This unique system consists of functionalized MSNs capable of releasing insulin when the concentration of sugar in blood exceeds healthy levels. The insulin-free nanoparticles are then up taken by pancreatic cells, and release inside of them another biomolecule that stimulates the production of more insulin. The in vivo application of this system for the treatment of diabetes requires further understanding on the biological behaviors of these nanoparticles in blood vessels. The research presented in this dissertation demonstrated the size and surface effects on the interaction of MSNs with red blood cell membranes, and discovered how the surface of the nanoparticles can be modified to improve their compatibility with red blood cells and avoid their dangerous side effects. In order to optimize the properties of MSN for applying them as efficient intracellular drug carriers it is necessary to understand the factors that can regulate their internalization into and exocytosis out of the cells. The correlation between the particle morphology and aggregation of MSNs to the effectiveness of cellular uptake is discussed and compared with different cell lines. The differences in the degree of exocytosis of MSNs between healthy and cancer cells is reported and found to be responsible for the asymmetric transfer of the particles between both cell types. The fundamental studies on the hemocompatibility, endo- and exocytosis of MSN along with its ability to sequentially release multiple therapeutics in response to different stimuli, allow us to propose MSN as an intravascular vehicle with a great potential for various biomedical applications

Robustness and edge addition strategy of air transport networks : a case study of 'the Belt and Road'

Air transportation is of great importance in "the Belt and Road" (the B&R) region. The achievement of the B&R initiative relies on the availability, reliability, and safety of air transport infrastructure. A fundamental step is to find the critical elements in network performance. Considering the uneven distributions of population and economy, the current literature focusing on centrality measures in unweighted networks is not sufficient in the B&R region. By differentiating power and centrality in the B&R region, our analysis leads to two conclusions: (1) Deactivating powerful nodes causes a larger decrease in efficiency than deactivating central nodes. This indicates that powerful nodes in the B&R region are more critical than central nodes for network robustness. (2) Strategically adding edges between high powerful and low powerful nodes can enhance the network's ability to exchange resources efficiently. These findings can be used to adjust government policies for air transport configuration to achieve the best network performance and the most cost effective

THEORIZING A TWO-SIDED ADOPTION MODEL FOR MOBILE MARKETING PLATFORMS

From a two-sided market perspective, this paper is aimed at proposing a conceptual model for analyzing user adoption behaviors towards mobile marketing platforms. Both the consumer side and the merchant side of the platforms are modeled based on extending classical theories with newly introduced factors reflecting cross network effects, and the two sides are integrated in the overall model which reveals the dynamic interaction between the evolution processes of the two user groups through the platform. An experimental investigation and a survey study are conducted to test the consumer side and the merchant side of the model, respectively, both using the structural equation modeling (SEM) method for statistic analysis. Results from the empirical tests demonstrate that the two-sided perspective is promising for interpreting the adoption and evolution mechanisms of mobile marketing platforms. The proposed model extends the current research theme of information systems adoption to a more comprehensive viewpoint of two-sided markets, while contributes to the literature of two-sided market theories by introducing behavioral considerations

Research of piezoelectric acoustic liner

The piezoelectric acoustic liner is a new type of acoustic liner that uses piezoelectric patches to replace the traditional mechanical structure. Its working principle is to change the resonator volume of acoustic liner by inverse piezoelectric effect. In this paper, the finite element method is used to analyze the deformation of piezoelectric patches and the acoustic performance of piezoelectric acoustic liner, when the piezoelectric patch deformation is 0.1 mm, the noise elimination frequency band offset of the acoustic liner is about 30 Hz, and related experiments are designed. The experimental results confirm that noise elimination frequency range of piezoelectric acoustic liner is 1100 Hz to 1300 Hz within the voltage range of 0 V to 200 V

Mesoporous Silica Nanoparticle-Based Double Drug Delivery System for Glucose-Responsive Controlled Release of Insulin and Cyclic AMP

A boronic acid-functionalized mesoporous silica nanoparticle-based drug delivery system (BA-MSN) for glucose-responsive controlled release of both insulin and cyclic adenosine monophosphate (cAMP) was synthesized. Fluorescein isothiocyanate-labeled, gluconic acid-modified insulin (FITC-G-Ins) proteins were immobilized on the exterior surface of BA-MSN and also served as caps to encapsulate cAMP molecules inside the mesopores of BA-MSN. The release of both G-Ins and cAMP was triggered by the introduction of saccharides. The selectivity of FITC-G-Ins release toward a series of carbohydrate triggers was determined to be fructose \u3e glucose \u3e other saccharides. The unique feature of this double-release system is that the decrease of FITC-G-Ins release with cycles can be balanced by the release of cAMP from mesopores of MSN, which is regulated by the gatekeeper effect of FITC-G-Ins. In vitro controlled release of cAMP was studied at two pH conditions (pH 7.4 and 8.5). Furthermore, the cytotoxicity of cAMP-loaded G-Ins-MSN with four different cell lines was investigated by cell viability and proliferation studies. The cellular uptake properties of cAMP-loaded FITC-BA-MSN with and without G-Ins capping were investigated by flow cytometry and fluorescence confocal microscopy. We envision that this glucose-responsive MSN-based double-release system could lead to a new generation of self-regulated insulin-releasing devices

Luciferase and Luciferin Co-immobilized Mesoporous Silica Nanoparticle Materials for Intracellular Biocatalysis

We report a gold nanoparticle (AuNP)-capped mesoporous silica nanoparticle (Au-MSN) platform for intracellular codelivery of an enzyme and a substrate with retention of bioactivity. As a proof-of-concept demonstration, Au-MSNs are shown to release luciferin from the interior pores of MSN upon AuNP uncapping in response to disulfide-reducing antioxidants and codeliver bioactive luciferase from the PEGylated exterior surface of Au-MSN to Hela cells. The effectiveness of luciferase-catalyzed luciferin oxidation and luminescence emission in the presence of intracellular ATP was measured by a luminometer. Overall, the chemical tailorability of the Au-MSN platform to retain enzyme bioactivity, the ability to codeliver enzyme and substrate, and the potential for imaging tumor growth and metastasis afforded by intracellular ATP- and glutathione-dependent bioluminescence make this platform appealing for intracellular controlled catalysis and tumor imaging

The FlySpeech Audio-Visual Speaker Diarization System for MISP Challenge 2022

This paper describes the FlySpeech speaker diarization system submitted to the second \textbf{M}ultimodal \textbf{I}nformation Based \textbf{S}peech \textbf{P}rocessing~(\textbf{MISP}) Challenge held in ICASSP 2022. We develop an end-to-end audio-visual speaker diarization~(AVSD) system, which consists of a lip encoder, a speaker encoder, and an audio-visual decoder. Specifically, to mitigate the degradation of diarization performance caused by separate training, we jointly train the speaker encoder and the audio-visual decoder. In addition, we leverage the large-data pretrained speaker extractor to initialize the speaker encoder