Nano-Enabled Antivirals for Overcoming Antibody Escaped Mutations Based SARS-CoV-2 Waves.

This review discusses receptor-binding domain (RBD) mutations related to the emergence of various SARS-CoV-2 variants, which have been highlighted as a major cause of repetitive clinical waves of COVID-19. Our perusal of the literature reveals that most variants were able to escape neutralizing antibodies developed after immunization or natural exposure, pointing to the need for a sustainable technological solution to overcome this crisis. This review, therefore, focuses on nanotechnology and the development of antiviral nanomaterials with physical antagonistic features of viral replication checkpoints as such a solution. Our detailed discussion of SARS-CoV-2 replication and pathogenesis highlights four distinct checkpoints, the S protein (ACE2 receptor coupling), the RBD motif (ACE2 receptor coupling), ACE2 coupling, and the S protein cleavage site, as targets for the development of nano-enabled solutions that, for example, prevent viral attachment and fusion with the host cell by either blocking viral RBD/spike proteins or cellular ACE2 receptors. As proof of this concept, we highlight applications of several nanomaterials, such as metal and metal oxide nanoparticles, carbon-based nanoparticles, carbon nanotubes, fullerene, carbon dots, quantum dots, polymeric nanoparticles, lipid-based, polymer-based, lipid-polymer hybrid-based, surface-modified nanoparticles that have already been employed to control viral infections. These nanoparticles were developed to inhibit receptor-mediated host-virus attachments and cell fusion, the uncoating of the virus, viral gene expression, protein synthesis, the assembly of progeny viral particles, and the release of the virion. Moreover, nanomaterials have been used as antiviral drug carriers and vaccines, and nano-enabled sensors have already been shown to enable fast, sensitive, and label-free real-time diagnosis of viral infections. Nano-biosensors could, therefore, also be useful in the remote testing and tracking of patients, while nanocarriers probed with target tissue could facilitate the targeted delivery of antiviral drugs to infected cells, tissues, organs, or systems while avoiding unwanted exposure of non-target tissues. Antiviral nanoparticles can also be applied to sanitizers, clothing, facemasks, and other personal protective equipment to minimize horizontal spread. We believe that the nanotechnology-enabled solutions described in this review will enable us to control repeated SAR-CoV-2 waves caused by antibody escape mutations.

High Potential of Aerosol-Made 3D Graphene-Based Composites for Enhanced Energy Storage.

Recently, many researchers have developed advanced energy storage and energy conversion systems to address the increased demand for energy resources. The performance of these electrochemical energy storage and conversion devices depends considerably on the properties of their unique electrode materials. Among electrode materials, graphene (GR) has attracted much attention due to its unique properties of high flexibility, a large specific surface area, and superior electric conductivity rates that are well-suited to energy storage systems. Specifically, aerosol-made 3D GR composites are known to be more resistant to compressive forces such as paper balls owing to their stronger and harder compressive tolerance levels and higher and more stable surface areas compared to 2D GR sheets. These unique properties of 3D GR composites result in enhanced electrochemical performances for energy storage systems. This review focuses on recent studies of aerosol-made 3D GR-based composites for energy storage systems such as supercapacitors, lithium-ion batteries, and sodium-ion batteries.

Stacking-Controlled Assembly of Cabbage-Like Graphene Microsphere for Charge Storage Applications.

Nanostructured graphene electrodes generally have a low density, which can limit the volumetric performance for energy storage devices. The liquid-phase mild reduction process of graphene oxide sheets is combined with the continuous aerosol densification process to produce high-density graphene agglomerates in the form of microspheres. The produced graphene assembly shows the cabbage-like morphology with a high density of 0.75 g cm-3 . In spite of such high density, the cabbage-like graphene microspheres have narrow-ranged mesopores and a high surface area. The cabbage-like graphene microsphere exhibits both high gravimetric and volumetric energy densities due to the optimized microstructure, which shows a high gravimetric capacitance of 177 F g-1 and volumetric capacitance of 117 F cm-3 in supercapacitors. As a cathode for lithium-ion capacitors, the cabbage-like graphene delivers a reversible capacity of ≈176 mAh g-1 . The stacking-control approach provides a new pathway to control the microstructure of the graphene assembly and corresponding charge storage characteristics for energy storage applications.

Human Motor System-Based Biohybrid Robot-On-a-Chip for Drug Evaluation of Neurodegenerative Disease.

Biohybrid robots have been developed for biomedical applications and industrial robotics. However, the biohybrid robots have limitations to be applied in neurodegenerative disease research due to the absence of a central nervous system. In addition, the organoids-on-a-chip has not yet been able to replicate the physiological function of muscle movement in the human motor system, which is essential for evaluating the accuracy of the drugs used for treating neurodegenerative diseases. Here, a human motor system-based biohybrid robot-on-a-chip composed of a brain organoid, multi-motor neuron spheroids, and muscle bundle on solid substrateis proposed to evaluate the drug effect on neurodegenerative diseases for the first time. The electrophysiological signals from the cerebral organoid induced the muscle bundle movement through motor neuron spheroids. To evaluate the drug effect on Parkinson's disease (PD), a patient-derived midbrain organoid is generated and incorporated into a biohybrid robot-on-a-chip. The drug effect on PD is successfully evaluated by measuring muscle bundle movement. The muscle bundle movement of PD patient-derived midbrain organoid-based biohybrid robot-on-a-chip is increased from 4.5 ± 0.99 µm to 18.67 ± 2.25 µm in response to levodopa. The proposed human motor system-based biohybrid robot-on-a-chip can serve as a standard biohybrid robot model for drug evaluation.

Facile synthesis of CuONPs using Citrus limon juice for enhancing antibacterial activity against methicillin-resistant Staphylococcus aureus, beta-lactamase and tetracycline-resistant Escherichia coli.

Antimicrobial resistance (AMR) resulting from indiscriminate use of antibiotics in various fields of agriculture such as livestock farming, aquaculture, and croup fields become an emerging catatroph for the health (human, animal) and environment. Among those, poultry farming has been considered as one of the major contributors of multidrug-resistant (MDR) bacteria. Focusing this, the present research is designed for green synthesis of copper oxide nanoparticles (CuONPs) with the aim of their application in antibiotic-free poultry farming for curving use of antibiotics in that sector. For that, antibacterial CuONPs were nanoformulated to decrease the required doses of bulk CuSO4. We used a CuSO4·5H2O solution as a Cu2+ source and Citrus limon juice as a reducing agent as well as capping agent. Particle yield was initially confirmed by the λmax specific to CuONPs (295 nm) using UV-Vis spectroscopy. The presence of the Cu-O group during particle formation and crystallinity with the purity of yielded NPs was confirmed with Fourier-transform infrared spectroscopy and X-ray diffractometry. The round to spherical CuONPs of 92-155 nm average size was confirmed with atomic force, scanning electron, and transmission electron microscopy. The concentration of yielded NPs was calculated with the dynamic light scattering. The physical characterization tools indicated a maximum CuONPs yield with a 0.001 M ion source with 15% reducing agents after 12 h reduction. Antibacterial effectivity was tested against methicillin-resistant Staphylococcus aureus and tetracycline- and beta-lactamase-resistant Escherichia coli, confirmed by PCR amplicon band at 163 bp, 643 bp, and 577 bp for the mecA, blaTEM-1 and tetA genes, respectively. An antibiogram assay of CuONPs showed a maximum zone of inhibition of 26 ± 0.5 mm for the synthesized particles. The minimum inhibitory and bactericidal concentrations were 1.6 µg ml-1 and 3.1 µg ml-1, respectively, for broad-spectrum application. Finally, the biocompatibility of CuONPs was determined by demonstrating a nonsignificant decrease of BHK-21 cell viability at <2 MIC doses for complying their future in vivo applicability.

Electrophysiological Monitoring of Neurochemical-Based Neural Signal Transmission in a Human Brain-Spinal Cord Assembloid.

Combining human brain organoids holds great potential in recapitulating the human brain's histological features and modeling neural disorders. However, current combined-brain organoid models focus on the internal interactions between different brain regions. In this study, we develop an engineered brain-spinal cord assembloid (eBSA) by coculturing cerebral organoids (COs) and motor neuron spheroids (MNSs). By connecting COs and MNSs, we generate a terminal for signal transfer from the brain to the whole body by mimicking the brain-spinal cord connection. After the formation of COs from human induced pluripotent stem cells and MNSs from human neural stem cells, MNSs are prepatterned into specific CO regions and assembled to form an eBSA. Caffeine serves as a neurochemical model to demonstrate neural signal transmission. When the MNSs in the eBSA contact the multielectrode array, the eBSA successfully shows an increased neural spiking speed on the motor neuron region by caffeine treatment, which means that neural stimulation signals transfer from the COs to MNSs. The neural stimulation effects of caffeine are tested on the MNSs only to prove the eBSA system's neural signal transmission, and there were no stimulus effects. Our results demonstrate that the eBSA system can monitor a caffeine-mediated excitatory signal as an output signal from the brain to the spinal cord. We believe that the eBSA system can be utilized as a screening platform to validate the stimulus signal transfer by neurochemicals. In addition, the accumulation of understanding of the neural signal transfer from CNS to PNS will provide better knowledge for controlling muscle actuators with the nervous system.

Electroactive nano-Biohybrid actuator composed of gold nanoparticle-embedded muscle bundle on molybdenum disulfide nanosheet-modified electrode for motion enhancement of biohybrid robot.

There have been several trials to develop the bioactuator using skeletal muscle cells for controllable biobybird robot. However, due to the weak contraction force of muscle cells, the muscle cells could not be used for practical applications such as biorobotic hand for carrying objects, and actuator of biohybrid robot for toxicity test and drug screening. Based on reported hyaluronic acid-modified gold nanoparticles (HA@GNPs)-embedded muscle bundle on PDMS substrate, in this study for augmented actuation, we developed the electroactive nano-biohybrid actuator composed of the HA@GNP-embedded muscle bundle and molybdenum disulfide nanosheet (MoS2 NS)-modified electrode to enhance the motion performance. The MoS2 NS-modified Au-coated polyimide (PI) electrode to be worked in mild pH condition for viable muscle cell was utilized as supporting- and motion enhancing- substrate since it was electrochemically active, which caused the movement of flexible PI electrode. The motion performance of this electroactive nano-biohybrid actuator by electrical stimulation was increased about 3.18 times compared with that of only HA@GNPs embedded-muscle bundle on bare PI substrate. The proposed electroactive nano-biohybrid actuator can be applied to the biorobotic hand and biohybrid robot.

Nanomaterial-Based Fluorescence Resonance Energy Transfer (FRET) and Metal-Enhanced Fluorescence (MEF) to Detect Nucleic Acid in Cancer Diagnosis.

Nucleic acids, including DNA and RNA, have received prodigious attention as potential biomarkers for precise and early diagnosis of cancers. However, due to their small quantity and instability in body fluids, precise and sensitive detection is highly important. Taking advantage of the ease-to-functionality and plasmonic effect of nanomaterials, fluorescence resonance energy transfer (FRET) and metal-enhanced fluorescence (MEF)-based biosensors have been developed for accurate and sensitive quantitation of cancer-related nucleic acids. This review summarizes the recent strategies and advances in recently developed nanomaterial-based FRET and MEF for biosensors for the detection of nucleic acids in cancer diagnosis. Challenges and opportunities in this field are also discussed. We anticipate that the FRET and MEF-based biosensors discussed in this review will provide valuable information for the sensitive detection of nucleic acids and early diagnosis of cancers.