Impact of E484Q and L452R Mutations on Structure and Binding Behavior of SARS-CoV-2 B.1.617.1 Using Deep Learning AlphaFold2, Molecular Docking and Dynamics Simulation.

During the outbreak of COVID-19, many SARS-CoV-2 variants presented key amino acid mutations that influenced their binding abilities with angiotensin-converting enzyme 2 (hACE2) and neutralizing antibodies. For the B.1.617 lineage, there had been fears that two key mutations, i.e., L452R and E484Q, would have additive effects on the evasion of neutralizing antibodies. In this paper, we systematically investigated the impact of the L452R and E484Q mutations on the structure and binding behavior of B.1.617.1 using deep learning AlphaFold2, molecular docking and dynamics simulation. We firstly predicted and verified the structure of the S protein containing L452R and E484Q mutations via the AlphaFold2-calculated pLDDT value and compared it with the experimental structure. Next, a molecular simulation was performed to reveal the structural and interaction stabilities of the S protein of the double mutant variant with hACE2. We found that the double mutations, L452R and E484Q, could lead to a decrease in hydrogen bonds and higher interaction energy between the S protein and hACE2, demonstrating the lower structural stability and the worse binding affinity in the long dynamic evolutional process, even though the molecular docking showed the lower binding energy score of the S1 RBD of the double mutant variant with hACE2 than that of the wild type (WT) with hACE2. In addition, docking to three approved neutralizing monoclonal antibodies (mAbs) showed a reduced binding affinity of the double mutant variant, suggesting a lower neutralization ability of the mAbs against the double mutant variant. Our study helps lay the foundation for further SARS-CoV-2 studies and provides bioinformatics and computational insights into how the double mutations lead to immune evasion, which could offer guidance for subsequent biomedical studies.

Molecularly Imprinted Silica-Coated CdTe Quantum Dots for Fluorometric Determination of Trace Chloramphenicol.

A dual recognition system with a fluorescence quenching of quantum dots (QDs) and specific recognition of molecularly imprinted polymer (MIP) for the detection of chloramphenicol (CAP) was constructed. MIP@SiO2@QDs was prepared by reverse microemulsion method with 3-aminopropyltriethoxysilane (APTS), tetraethyl orthosilicate (TEOS) and QDs being used as the functional monomer, cross-linker and signal sources, respectively. MIP can specifically recognize CAP, and the fluorescence of QDs can be quenched by CAP due to the photo-induced electron transfer reaction between CAP and QDs. Thus, a method for the trace detection of CAP based on MIP@SiO2@QDs fluorescence quenching was established. The fluorescence quenching efficiency of MIP@SiO2@QDs displayed a desirable linear response to the concentration of CAP in the range of 1.00~4.00 × 102 µmol × L-1, and the limit of detection was 0.35 µmol × L-1 (3σ, n = 9). Importantly, MIP@SiO2@QDs presented good detection selectivity owing to specific recognition for CAP, and was successfully applied to quantify CAP in lake water with the recovery ranging 102.0~104.0%, suggesting this method has the promising potential for the on-site detection of CAP in environmental waters.

Photoelectrochemical Aptasensors Constructed with Photosensitive PbS Quantum Dots/TiO2 Nanoparticles for Detection of Kanamycin.

Kanamycin (Kana) is widely used as a veterinary medicine and its abuse causes a serious threat to human health, raising the urgent demand for detection of residual Kana in animal-derived food with high specificity and sensitivity. Here, we developed a photoelectrochemical (PEC) biosensor for rapid quantification of Kana, with lead sulfide quantum dots/titanium dioxide nanoparticles (PbS QDs/TiO2 NPs) as a photosensitive composite, a Kana-specific DNA aptamer as a functional sensor, and ruthenium(III) hexaammine (Ru(NH3)63+) as a signal booster. To prepare the PEC aptasensor, TiO2 NPs, PbS QDs, and polyethyleneimine (PEI) were respectively used to modify the indium tin oxide electrode, and then the amine-terminated aptamer probe was connected to the PEI via glutaraldehyde. Finally, Ru(NH3)63+ was attached on the surface of the aptamer to increase the photocurrent intensity. When Kana binds competitively with Ru(NH3)63+ to the aptamer immobilized on the surface of the aptasensor, Ru(NH3)63+ will be released from the aptamer, resulting in a decrease of the photocurrent signal. This PEC aptasensor exhibits a good linear relationship between the photocurrent shift and the logarithm of Kana concentration within the range of 1.0-300.0 nmol L-1, and the detection limit is 0.161 nmol L-1. Importantly, the PEC aptasensor presented good detection selectivity owing to specific interaction with Kana and was successfully implemented to quantify Kana in honey and milk, suggesting that the PEC aptasensor has the potential of rapid detection of residual Kana in animal-derived foods.

Ni/Co bimetallic organic framework nanosheet assemblies for high-performance electrochemical energy storage.

Nickel-cobalt organic framework (denoted as NiCo-MOF) nanosheet assemblies are prepared through a controllable one-pot hydrothermal synthesis procedure at 150 °C. The as-prepared samples are directly employed as electrode materials for electrochemical energy storage (EES), and exhibit excellent electrochemical performance. Among these samples, NiCo-MOF-1 displays a high capacity of 100.18 mA h g-1 (901.60 F g-1), and obtains a capacity retention of 81.00% over 3000 cycles at 5 A g-1. Likewise, in an aqueous device, NiCo-MOF-1//AC delivers a discharge capacity of 83.75 mA h g-1, and also exhibits a good cycling life (74.14% retention after 3000 cycles). These results demonstrate that multilayer NiCo-MOF nanosheet assemblies are potential electrode materials for EES.

Ratiometric pH Sensing and Imaging in Living Cells with Dual-Emission Semiconductor Polymer Dots.

Polymer dots (Pdots) represent newly developed semiconductor polymer nanoparticles and exhibit excellent characteristics as fluorescent probes. To improve the sensitivity and biocompatibility of Pdots ratiometric pH biosensors, we synthesized 3 types of water-soluble Pdots: Pdots-PF, Pdots-PP, and Pdots-PPF by different combinations of fluorescent dyes poly(9,9-dioctylfluorenyl-2,7-diyl) (PFO), poly[(9,9-dioctyl-fluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1',3}-thiadazole)] (PFBT), and fluorescein isothiocyanate (FITC). We found that Pdots-PPF exhibits optimal performance on pH sensing. PFO and FITC in Pdots-PPF produce pH-insensitive (λ = 439 nm) and pH-sensitive (λ = 517 nm) fluorescence respectively upon a single excitation at 380 nm wavelength, which enables Pdots-PPF ratiometric pH sensing ability. Förster resonance energy transfer (FRET) together with the use of PFBT amplify the FITC signal, which enables Pdots-PPF robust sensitivity to pH. The emission intensity ratio (I517/I439) of Pdots-PPF changes linearly as a function of pH within the range of pH 3.0 to 8.0. Pdots-PPF also possesses desirable reversibility and stability in pH measurement. More importantly, Pdots-PPF was successfully used for cell imaging in Hela cells, exhibiting effective cellular uptake and low cytotoxicity. Our study suggests the promising potential of Pdots-PPF as an in vivo biomarker.

Novel fluorescent sensor using molecularly imprinted silica microsphere-coated CdSe@CdS quantum dots and its application in the detection of 2,4,6-trichlorophenol from environmental water samples.

In this study, a high fluorescence sensitivity and selectivity, molecularly imprinted nanofluorescent polymer sensor (MIP@SiO2 @QDs) was prepared using a reverse microemulsion method. 2,4,6-Trichlorophenol (2,4,6-TCP) was detected using fluorescence quenching. Tetraethyl orthosilicate (TEOS), quantum dots (QDs) and 3-aminopropyltriethoxysilane (APTS) were used as cross-linker, signal sources and functional monomer respectively. The sensor (MIP@SiO2 @QDs) and the non-imprinted polymer sensor (NIP@SiO2 @QDs) were characterized using infra-red (IR) analysis, X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The selectivity of MIP@SiO2 @QDs was examined by comparing 2,4,6-TCP with other similar functional substances including 2,4-dichlorophenol (2,4-DCP), 2,6-dichlorophenol (2,6-DCP) and 4-chlorophenol (4-CP). Results showed that MIP@SiO2 @QDs had better selectivity for 2,4,6-TCP than the other compounds. Fluorescence quenching efficiency displayed a good linear response at the 2,4,6-TCP concentration range 5-1000 µmol/L. The limit of detection (LOD) was 0.9 µmol/L (3σ, n = 9). This method was equally applicable for testing actual samples with a recovery rate of 98.0-105.8%. The sensor had advantages of simple pretreatment, good sensitivity and selectivity, and wide linear range and could be applied for the rapid detection of 2,4,6-TCP in actual samples.