Search

Abstract Direct imaging of single‐molecule and its movement is of fundamental importance in biology, but challenging. Herein, aided by the nanoconfinement effect and resultant high reaction activity within metal–organic frameworks (MOFs), the designed Ru(bpy)32+ embedded MOF complex (RuMOFs) exhibits bright electrochemiluminescence (ECL) emission permitting high‐quality imaging of ECL events at single molecule level. By labeling individual proteins of living cells with single RuMOFs, the distribution of membrane tyrosine‐protein‐kinase‐like7 (PTK7) proteins at low‐expressing cells is imaged via ECL. More importantly, the efficient capture of ECL photons generated inside the MOFs results in a stable ECL emission up to 1 h, allowing the in operando visualization of protein movements at the cellular membrane. As compared with the fluorescence observation, near‐zero ECL background surrounding the target protein with the ECL emitter gives a better contrast for the dynamic imaging of discrete protein movement. This achievement of single molecule ECL dynamic imaging using RuMOFs will provide a more effective nanoemitter to observe the distribution and motion of individual proteins at living cells.

Neural interfaces provide a window for bio-signal modulation and recording with the assistance of neural microelectrodes. However, shrinking the size of electrodes results in high electrochemical impedance and low capacitance, thus limiting the stimulation/recording efficiency. In order to achieve critical stability and low power consumption, here, nanocone-shaped platinum (Pt) with an extensive surface area is proposed as an adhesive layer on a bare Pt substrate, followed by the deposition of a thin layer of iridium oxide (IrOx) to fabricate high-performance nanocone-array-based Pt-IrOx neural microelectrodes (200 μm in diameter). A uniform nanocone-shaped Pt with significant roughness is created via controlling the ratio of NH4+ and Pt4+ ions in the electrolyte, which can be widely applicable for batch production on multichannel flexible microelectrode arrays (fMEAs) and various substrates with different dimensions. The Pt-IrOx nanocomposite-coated microelectrode presents a significantly low impedance down to 0.72 ± 0.04 Ω cm2 at 1 kHz (reduction of ~92.95%). The cathodic charge storage capacity (CSCc) and charge injection capacity (CIC) reaches up to 52.44 ± 2.53 mC cm−2 and 4.39 ± 0.36 mC cm−2, respectively. Moreover, superior chronic stability and biocompatibility are also observed. The modified microelectrodes significantly enhance the adhesion of microglia, the major immune cells in the central nervous system. Therefore, such a coating strategy presents great potential for biomedical and other practical applications.

Energy metabolism is highly interdependent with adaptive cell migration in vivo. Mechanical confinement is a critical physical cue that induces switchable migration modes of the mesenchymal-to-amoeboid transition (MAT). However, the energy states in distinct migration modes, especially amoeboid-like stable bleb (A2) movement, remain unclear. In this report, we developed multivalent DNA framework-based nanomachines to explore strategical mitochondrial trafficking and differential ATP levels during cell migration in mechanically heterogeneous microenvironments. Through single-particle tracking and metabolomic analysis, we revealed that fast A2-moving cells driven by biomimetic confinement recruited back-end positioning of mitochondria for powering highly polarized cytoskeletal networks, preferentially adopting an energy-saving mode compared with a mesenchymal mode of cell migration. We present a versatile DNA nanotool for cellular energy exploration and highlight that adaptive energy strategies coordinately support switchable migration modes for facilitating efficient metastatic escape, offering a unique perspective for therapeutic interventions in cancer metastasis. [ABSTRACT FROM AUTHOR]

Drug metabolism is an orchestrated process in which drugs are metabolized and disposed through a series of specialized enzymes and transporters. Alterations in the expression and/or activity of these enzymes and transporters can affect the bioavailability (pharmacokinetics, or PK) and therapeutic efficacy (pharmacodynamics, or PD) of drugs. Recent studies have suggested that the long non-coding RNAs (lncRNAs) are highly relevant to drug metabolism and drug resistance, including chemo-resistance in cancers, through the regulation of drug metabolism and disposition related genes. This review summarizes the regulation of enzymes, transporters, or regulatory proteins involved in drug metabolism by lncRNAs, with a particular emphasis on drug metabolism and chemo-resistance in cancer patients. The perspective strategies to integrate multi-dimensional pharmacogenomics data for future in-depth analysis of drug metabolism related lncRNAs are also proposed. Understanding the role of lncRNAs in drug metabolism will not only facilitate the identification of novel regulatory mechanisms, but also enable the discovery of lncRNA-based biomarkers and drug targets to personalize and improve the therapeutic outcome of patients, including cancer patients. KEY WORDS: LncRNA, Drug metabolism, Chemo-resistance, Xenobiotic receptor, Regulation

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected billions of individuals and is the cause of the current global coronavirus disease 2019 (COVID-19) pandemic. We previously developed an mRNA vaccine (LVRNA009) based on the S protein of the Wuhan-Hu-1 strain; the phases I and II clinical trials showed that LVRNA009 has a promising safety and immunogenicity profile. In order to counteract the immune escape by SARS-CoV-2 variants of concern, a panel of mRNA vaccines was developed based on the S proteins of the Wuhan-Hu-1, Delta, Omicron BA.1, BA.2, and BA.5 strains, and each vaccine’s protective potency against the virus variants was evaluated. Furthermore, to achieve excellent neutralization against SARS-CoV-2 variants, bivalent vaccines were developed and tested against the variants. We found that the monovalent Wuhan-Hu-1 or the Delta vaccines could induce high level of neutralization antibody and protect animals from the infection of the SARS-CoV-2 Wuhan-Hu-1 or Delta strains, respectively. However, serum samples from mice immunized with monovalent Delta vaccine showed relatively low virus neutralization titers (VNTs) against the pseudotyped virus of the Omicron strains. Serum samples from mice immunized with bivalent Delta/BA.1 vaccine had high VNTs against the pseudotyped Wuhan-Hu-1, Delta, and BA.1 strains but low VNTs against BA.2 and BA.5 (p < 0.05). Serum samples from mice immunized with Delta/BA.2 vaccine had high VNTs against the pseudotyped Wuhan-Hu-1, Delta, BA.1 and BA.2 strains but low VNTs against BA.5. Finally, serum samples from mice immunized with Delta/BA.5 vaccine had high VNTs against all the tested pseudotyped SARS-CoV-2 strains including the Wuhan-Hu-1, Delta, and Omicron variants (p > 0.05). Therefore, a bivalent mRNA vaccine with Delta/BA.5 combination is promising to provide broad spectrum immunity against all VOCs.