Plasmonic Imaging of Multivalent NTD-Nucleic Acid Interactions for Broad-Spectrum Antiviral Drug Analysis.

The discovery and identification of broad-spectrum antiviral drugs are of great significance for blocking the spread of pathogenic viruses and corresponding variants of concern. Herein, we proposed a plasmonic imaging-based strategy for assessing the efficacy of potential broad-spectrum antiviral drugs targeting the N-terminal domain of a nucleocapsid protein (NTD) and nucleic acid (NA) interactions. With NTD and NA conjugated gold nanoparticles as core and satellite nanoprobes, respectively, we found that the multivalent binding interactions could drive the formation of core-satellite nanostructures with enhanced scattering brightness due to the plasmonic coupling effect. The core-satellite assembly can be suppressed in the presence of antiviral drugs targeting the NTD-NA interactions, allowing the drug efficacy analysis by detecting the dose-dependent changes in the scattering brightness by plasmonic imaging. By quantifying the changes in the scattering brightness of plasmonic nanoprobes, we uncovered that the constructed multivalent weak interactions displayed a 500-fold enhancement in affinity as compared with the monovalent NTD-NA interactions. We demonstrated the plasmonic imaging-based strategy for evaluating the efficacy of a potential broad-spectrum drug, PJ34, that can target the NTD-NA interactions, with the IC50 as 24.35 and 14.64 µM for SARS-CoV-2 and SARS-CoV, respectively. Moreover, we discovered that ceftazidime holds the potential as a candidate drug to inhibit the NTD-NA interactions with an IC50 of 22.08 µM from molecular docking and plasmonic imaging-based drug analysis. Finally, we validated that the potential antiviral drug, 5-benzyloxygramine, which can induce the abnormal dimerization of nucleocapsid proteins, is effective for SARS-CoV-2, but not effective against SARS-CoV. All these demonstrations indicated that the plasmonic imaging-based strategy is robust and can be used as a powerful strategy for the discovery and identification of broad-spectrum drugs targeting the evolutionarily conserved viral proteins.

Tuning the Cellular Uptake and Retention of Rhodamine Dyes by Molecular Engineering for High-Contrast Imaging of Cancer Cells.

Probes allowing high-contrast discrimination of cancer cells and effective retention are powerful tools for the early diagnosis and treatment of cancer. However, conventional small-molecule probes often show limited performance in both aspects. Herein, we report an ingenious molecular engineering strategy for tuning the cellular uptake and retention of rhodamine dyes. Introduction of polar aminoethyl leads to the increased brightness and reduced cellular uptake of dyes, and this change can be reversed by amino acetylation. Moreover, these modifications allow cancer cells to take up more dyes than normal cells (16-fold) through active transport. Specifically, we further improve the signal contrast (56-fold) between cancer and normal cells by constructing activatable probes and confirm that the released fluorophore can remain in cancer cells with extended time, enabling long-term and specific tumor imaging.

Single-particle rotational sensing for analyzing the neutralization activity of antiviral antibodies.

Due to the pathogen-specific targeting, neutralization capabilities, and enduring efficacy, neutralizing antibodies (NAs) have received widespread attentions as a critical immunotherapeutic strategy against infectious viruses. However, because of the high variability and complexity of pathogens, rapid determination of neutralization activity of antiviral antibodies remains a challenge. Here, we report a new method, named as out-of-plane polarization imaging based single-particle rotational sensing, for rapid analysis of neutralization activity of antiviral antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using the spike protein functionalized gold nanorods (AuNRs) and angiotensin-converting enzyme 2 (ACE2) coated gold nanoparticles (AuNPs) as the rotational sensors and chaperone probes, we demonstrated the single-particle rotational sensing strategy for the measurement of rotational diffusion coefficient of the chaperone-bound rotational sensors caused by the specific spike protein-ACE2 interactions. This enables us to measure the neutralizing activity of neutralizing antibody from the analysis of dose-dependent changes in rotational diffusion coefficient (Dr) of the rotational sensors upon the treatment of SARS-CoV-2 antibody. With this technique, we achieved the quantitative determination of neutralization activity of a commercially available SARS-CoV-2 antibody (IC50, 294.1 ng/mL) with satisfying accuracy and anti-interference ability. This simple and robust method holds the potential for rapid and accurate evaluation of neutralization activity against different pathogenic viruses.

High-performance phononic crystal sensing structure for acetone solution concentration sensing.

A two-dimensional phononic crystal sensor model with high-quality factor and excellent sensitivity for sensing acetone solutions and operating at 25-45 kHz is proposed. The model for filling solution cavities is based on reference designs of quasi-crystal and gradient cavity structures. The transmission spectrum of sensor is simulated by the finite element method. High-quality factor of 45,793.06 and sensitivity of 80,166.67 Hz are obtained for the acetone concentration with 1-9.1%, and quality factor of 61,438.09 and sensitivity of 24,400.00 Hz are obtained for the acetone concentration range of 10-100%, which indicated the sensor could still achieve high sensitivity and quality factor at operating frequencies from 25 to 45 kHz. To verify the application of the sensor to sensing other solutions, the sensitivity for sound velocity and density is calculated as 24.61 m-1 and 0.7764 m3/(kg × s), respectively. It indicates the sensor is sensitive to acoustic impedance changes of the solution and equally suitable for sensing other solutions. The simulation results reveal the phononic crystal sensor possessed high-performance in composition capture in pharmaceutical production and petrochemical industry, which can provide theoretical reference for the design of new biochemical sensors for reliable detection of solution concentration.

Tunable characteristics of low-frequency bandgaps in two-dimensional multivibrator phononic crystal plates under prestrain.

In view of the influence of variability of low-frequency noise frequency on noise prevention in real life, we present a novel two-dimensional tunable phononic crystal plate which is consisted of lead columns deposited in a silicone rubber plate with periodic holes and calculate its bandgap characteristics by finite element method. The low-frequency bandgap mechanism of the designed model is discussed simultaneously. Accordingly, the influence of geometric parameters of the phononic crystal plate on the bandgap characteristics is analyzed and the bandgap adjustability under prestretch strain is further studied. Results show that the new designed phononic crystal plate has lower bandgap starting frequency and wider bandwidth than the traditional single-sided structure, which is due to the coupling between the resonance mode of the scatterer and the long traveling wave in the matrix with the introduction of periodic holes. Applying prestretch strain to the matrix can realize active realtime control of low-frequency bandgap under slight deformation and broaden the low-frequency bandgap, which can be explained as the multiple bands tend to be flattened due to the localization degree of unit cell vibration increases with the rise of prestrain. The presented structure improves the realtime adjustability of sound isolation and vibration reduction frequency for phononic crystal in complex acoustic vibration environments.

Time-delay signature characteristics of the chaotic output from an optoelectronic oscillator by introducing an optical feedback.

In this work, via autocorrelation function (ACF) and permutation entropy (PE) methods, we numerically investigate the time-delay signature (TDS) characteristics of the chaotic signal output from an optoelectronic oscillator (OEO) after introducing an extra optical feedback loop. The results demonstrate that, for such a chaotic system, both the optoelectronic feedback with a delay time of T1 and the optical feedback with a delay time of T2 contribute to the TDS of generated chaos. The TDS of the chaotic signal should be evaluated within a large time window including T1 and T2 by the strongest peak in the ACF curve of the chaotic signal, and the strongest peak may locate at near T1 or T2. Through mapping the evolution of the TDS in the parameter space of the optical feedback strength and time, certain optimized parameter regions for achieving a chaotic signal with a relatively weak TDS can be determined.