Investigation of the Physical and Physiochemical Relationships in Nanoparticles and their Attributions to Antimicrobial Activities

Antibiotic resistance is one of the greatest threats to global health, as bacteria are becoming increasingly resistant to antibiotics leading to failure of treatments. This PhD project investigated the physical, chemical and physiochemical properties of a total of eleven potential antimicrobial nanomaterials. Some of which were engineered with antiviral function using TesimaTM thermal plasma technology, others were commercially available. The aims of this project are to select 2-3 nanomaterial candidates with the best physiochemical and antimicrobial performances and to exploit them into a single antimicrobial formulation, which would generically deactivate a wide spectrum of pathogens and suitable to be applied as a coating/impregnating agent for the applications in biomedical instrument. In order to understand how nanoparticles such as Tungsten (W), Copper (Cu), Silver (Ag), Zinc (Zn) and their derivatives lead to the inactivation of Gram-negative bacteria (P. aeruginosa) and Gram-positive bacteria (S. aureus), different instrumentation analyses were used to examine these nanoparticles in powder and aqueous suspension forms. These analyses were then used to reflect on the associated antimicrobial testing results. SEM was used to reveal the shapes and approximate sizes of the nanoparticle powder. Powder X-ray diffraction identified the exact crystal phases in the raw nanopowders. FTIR and Raman spectroscopy were used to trace the presence of organic impurities. ICP-OES was used to quantify the elemental compositions in nanoparticles and the amount of metallic ions saturated in the aqueous media. Nanoparticle tracking analysis (NTA) was used to not measure the concentration and size distribution of nanoparticles in the aqueous media, but also reveal the difference between nanoparticle suspensions and their powder forms. Zetasizer was used to measure their surface charge, which affects their stability. The physiochemical study provided details of the hydrodynamic particle sizes, distributions and stabilities of the selected materials, which had direct reflection on their exposure and static interactions to different microbial cells. Different dispersing methods were investigated, in order to optimize the processing parameters to obtain uniform and stable nanoparticle suspensions, of which are the basic requirements for enhancing fabrication compatibility and antimicrobial efficacy with hybridizable substrates for biomedical devices. In general, different shapes of nanoparticles were found in both commercial and engineered samples, nevertheless, they all met the physical criteria as nanoparticles. Engineered nanoparticles, especially the Ag nanoparticles, appeared to be less pure when comparing to the commercial ones, however it was found to be the most effective materials against P. aeruginosa. The ion release as the main antimicrobial mechanism performed differently depending on types of nanoparticle forms, pH levels and salt effect in the aqueous media. In this study, the pH values of all samples in water were basically neutral, and the zeta potential values were mostly negative. Overall, the best way to obtain stable nanoparticle suspension is to disperse raw nanoparticle in aqueous medium using high frequency liquid processor (sonicator) for 2 minutes in the present of surface treatment. NTA detected that most of the tested metallic nanoparticles and formulations prepared with using this method showed to exhibit good dispersion, while excessive sonication can cause overheating, particle collisions and contamination. Besides, a processing method based on microwave reactor was developed for poorly dispersed Cu nanoparticle, which enhanced dispersion with increasing the heating temperature. The level of antimicrobial efficacy appeared to be highly dependent on their hydrodynamic sizes and stability. A 30-minute dispersant measurement using NTA showed good antimicrobial nanoparticle agents (Ag, CuAg and AMNP2 suspensions) remained relatively high concentrations and small sizes in the end. The combination of multi-elements played a stronger role in killing bacteria. Therefore, alloy nanoparticles, such as CuAg and CuZn showed the most promising physiochemical and antimicrobial characteristics. Their formulas were calculated (CuAg42 and Cu2.3Zn1) based on the atomic ratio of elements from elemental analysis

TSAM: A Two-Stream Attention Model for Causal Emotion Entailment

Causal Emotion Entailment (CEE) aims to discover the potential causes behind an emotion in a conversational utterance. Previous works formalize CEE as independent utterance pair classification problems, with emotion and speaker information neglected. From a new perspective, this paper considers CEE in a joint framework. We classify multiple utterances synchronously to capture the correlations between utterances in a global view and propose a Two-Stream Attention Model (TSAM) to effectively model the speaker's emotional influences in the conversational history. Specifically, the TSAM comprises three modules: Emotion Attention Network (EAN), Speaker Attention Network (SAN), and interaction module. The EAN and SAN incorporate emotion and speaker information in parallel, and the subsequent interaction module effectively interchanges relevant information between the EAN and SAN via a mutual BiAffine transformation. Extensive experimental results demonstrate that our model achieves new State-Of-The-Art (SOTA) performance and outperforms baselines remarkably

Antiviral Efficacy of Metal and Metal Oxide Nanoparticles against the Porcine Reproductive and Respiratory Syndrome Virus

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Porcine reproductive and respiratory syndrome viruses (PRRSV) are responsible for one of the most economically important diseases affecting the global pig industry. On-farm high-efficiency particulate air (HEPA) filtration systems can effectively reduce airborne transmission of PRRSV and the incidence of PRRS, but they are costly, and their adoption is limited. Therefore, there is a need for low-cost alternatives, such as antimicrobial filters impregnated with antiviral nanoparticles (AVNP). During the past 10 years, tailored intermetallic/multi-elemental AVNP compositions have demonstrated effective performance against human viruses. In this study, a panel of five AVNP was evaluated for viricidal activity against PRRSV. Three AVNP materials: AVNP2, copper nanoparticles (CuNP), and copper oxide nanoparticles (CuONP), were shown to exert a significant reduction (>99.99%) in virus titers at 1.0% (w/v) concentration. Among the three, CuNP was the most effective at lower concentrations. Further experiments revealed that AVNP generated significant reductions in viral titers within just 1.5 min. For an optimal reduction in viral titers, direct contact between viruses and AVNP was required. This was further explained by the inert nature of these AVNP, where only negligible leaching concentrations of Ag/Cu ions (0.06–4.06 ppm) were detected in AVNP supernatants. Real-time dynamic light scatting (DLS) and transmission electron microscopic (TEM) analyses suggested that the mono-dispersive hydrodynamic behavior of AVNPs may have enhanced their antiviral activity against PRRSV. Collectively, these data support the further evaluation of these AVNP as candidate nanoparticles for incorporation into antimicrobial air-filtration systems to reduce transmission of PRRSV and other airborne pathogens.Peer reviewe

Designing a novel high-throughput AlphaLISA assay to quantify plasma NHERF1 as a non-small cell lung cancer biomarker

NHERF1 might play a significant role in biological processes including oncogenic transformation and metastasis. Owing to the lack of highly sensitive and quantitative methods of NHERF1 in human plasma, there have been few reports on the plasma levels of NHERF1 and its correlation with cancer. Here, a novel amplified luminescent proximity homogeneous immunoassay (AlphaLISA) has been developed and validated for the quantification of NHERF1 in human plasma. This assay was based on an AlphaScreen detection technique with two different anti-NHERF1 antibodies coupled to donor and acceptor beads, respectively. The developed AlphaLISA assay was further optimized and validated in terms of linearity, limit of detection (LOD), limit of quantification (LOQ), precision, recovery, selectivity and interferences. The linear range of NHERF1 in human plasma was 5.00–100 ng mL−1, with an LOD of 2.00 ng mL−1. This AlphaLISA assay has been successfully applied to the quantification of NHERF1 in the plasma from 75 patients with non-small cell lung cancer (NSCLC). The levels of NHERF1 protein in plasma from patients with NSCLC were significantly higher than those in the healthy group (p = 0.0004). Based on the evaluation of the ROC curves, measuring the content of NHERF1 in human plasma could provide a potential diagnostic tool for NSCLC

Differential expression and functions of Ehm2 transcript variants in lung adenocarcinoma

Ehm2 [also known as erythrocyte membrane protein band 4.1‑like protein 4B (EPB41L4B)] is a member of the NF2/ERM/4.1 superfamily. The overexpression of Ehm2 has been observed in metastatic cancer cells. Through alternative splicing, the Ehm2 gene produces two transcript variants that encode the two different isoforms, Ehm2/1 and Ehm2/2. The biological functions of these different Ehm2 transcript variants remain unclear. The present study aimed to determine the expression of the Ehm2 variants in lung adenocarcinoma and their involvement in the disease progression of the patients. The expression of Ehm2 transcript variants in human lung adenocarcinoma tissues was analyzed using immunohistochemistry and western blot analysis. Ehm2 variants were overexpressed or knocked down in A549 human lung adenocarcinoma cells. The consequent effects of the genetic modifications on the cellular functions of lung cancer cells were then examined using in vitro cell viability, invasion and migration assays. The expression of epithelial‑mesenchymal transition (EMT)‑related markers was evaluated by western blot analysis in the cell models. The association of Ehm2 variant expression with patient survival was analyzed using Kaplan‑Meier survival analysis. The expression of Ehm2/1 was significantly decreased in lung cancers compared with the paired normal lung tissues (P<0.05), while the Ehm2/2 protein levels were higher in the tumors than in the paired normal lung tissues, although this was not statistically significant. The overexpression of Ehm2/1 exerted inhibitory effects, while the knockdown of Ehm2/1 promoted the growth, invasion and migration of A549 cells in vitro. Ehm2/2 was expressed at low levels in the A549 cells and the enforced expression of Ehm2/2 significantly increased the invasiveness and migration of the A549 cells. Immunofluorescence staining revealed that Ehm2/1 was confined to the plasma membrane, while Ehm2/2 was observed at both the plasma membrane and cytoplasm. The overexpression of Ehm2/1 resulted in the upregulation of the epithelial marker, E‑cadherin, and in the decreased expression of the mesenchymal markers, N‑cadherin and Snail1, while the knockdown of Ehm2/1 and the enforced expression of Ehm2/2 had the opposite effects on the protein levels of EMT‑related markers. Kaplan‑Meier survival analysis revealed that higher Ehm2/1 transcript levels were associated with the longer survival of patients with lung adenocarcinoma, while the lower expression of Ehm2/2 exhibited a similar association with patient survival. Taken together, the two Ehm2 variants appear to be differentially expressed in lung adenocarcinoma. Ehm2/1 may function as a putative tumor suppressor in the disease progression of lung adenocarcinoma, while Ehm2/2 may have an opposite function

Exploitation of antimicrobial nanoparticles and their applications in biomedical engineering

Antibiotic resistance is a major threat to public health which contributes largely to increased mortality rates and costs in hospitals. The severe and wide spread of antibiotic resistance results in limited treatment to effectively combat antibiotic-resistant pathogens. Nanoparticles have different or enhanced properties in contrast to their bulk material, including antimicrobial efficacy towards a broad range of microorganisms. Their beneficial properties can be utilised in various bioengineering technologies, thus antimicrobial nanoparticles may provide an alternative to challenge antibiotic resistance. Currently nanoparticles have been incorporated into materials, such as fibres, glass and paints. However, more research is required to fully elucidate the mechanisms of action and to further advance for biomedical applications. This paper reviews the antimicrobial efficacies and the intrinsic properties of different metallic nanoparticles; their potential mechanisms of action against certain types of harmful pathogens and how these properties may be utilised in biomedical and healthcare products with aims to reduce cross contaminations, disease transmissions and usage of antibiotics.Peer reviewe

A low-radix and low-diameter 3D interconnection network design

Interconnection plays an important role in performance and power of CMP designs using deep sub-micron technology. The network-on-chip (NoCs) has been proposed as a scalable and high-bandwidth fabric for interconnect design. The advent of the 3D technology has provided further opportunity to reduce on-chip communication delay. However, the design of the 3D NoC topologies has important distinctions from 2D NoCs or off-chip interconnection networks. First, current 3D stacking technology allows only vertical inter-layer links. Hence, there cannot be direct connections between arbitrary nodes in different layers — the vertical connection topology are essentially fixed. Second, the 3D NoC is highly constrained by the complexity and power of routers and links. Hence, low-radix routers are preferred over high-radix routers for lower power and better heat dissipation. This implies long network latency due to high hop counts in network paths. In this paper, we design a low-diameter 3D network using low-radix routers. Our topology leverages long wires to connect remote intra-layer nodes. We take advantage of the start-of-the-art one-hop vertical communication design and utilize lateral long wires to shorten network paths. Effectively, we implement a small-to-medium sized clique network in different layers of a 3D chip. The resulting topology generates a diameter of 3-hop only network, using routers of the same radix as 3D mesh routers. The proposed network shows up to 29 % of network latency reduction, up to 10 % throughput improvement, and up to 24 % energy reduction, when compared to a 3D mesh network. 1