The pandemic of coronavirus disease 2019 (COVID-19) highlights the importance of rapid and sensitive diagnostics of viral infection that enables the efficient tracing of cases and the implementation of public health measures for disease containment. The immediate actions from both academia and industry have led to the development of many COVID-19 diagnostic systems that have secured fast-track regulatory approvals and have been serving our healthcare frontlines since the early stage of the pandemic. On diagnostic technologies, many of these clinically validated systems have significantly benefited from the recent advances in micro-and nanotechnologies in terms of platform design, analytical method, and system integration and miniaturization. The continued development of new diagnostic platforms integrating micro-and nanocomponents will address some of the shortcomings we have witnessed in the existing COVID-19 diagnostic systems. This Perspective reviews the previous and ongoing research efforts on developing integrated microand nanosystems for nucleic acid-based virus detection, and highlights promising technologies that could provide better solutions for the diagnosis of COVID-19 and other viral infectious diseases. With the summary and outlook of this rapidly evolving research field, we hope to inspire more research and development activities to better prepare our society for future public health crises.

Cyclin-dependent kinase 9 (CDK9), which regulates transcriptional elongation, is an attractive therapeutic target for many cancers, especially for cancers driven by transcriptional dysregulation. In particular, CDK9 promotes RNA polymerase II pause/release, a rate-limiting step in normal transcriptional regulation that is frequently dysregulated in cancers. Emerging evidence indicates that selective CDK9 inhibition or degradation may provide a therapeutic benefit against certain cancers. Indeed, the development of CDK9 modulators (inhibitors and degraders) has attracted great attention, with several molecules currently under clinical development. This review provides an overview of recent advances in CDK9 modulators in general, with special emphasis on compounds under clinical evaluation and new emerging strategies, such as proteolysis targeting chimeras (PROTACs).

Accurate, rapid, and low-cost molecular diagnostics is essential in managing outbreaks of infectious diseases, such as the pandemic of coronavirus disease (COVID-19). Accordingly, microfluidic paper-based analytical devices (μPADs) have emerged as promising diagnostic tools. Among the extensive efforts to improve the performance and usability of μPADs, electrochemical impedance spectroscopy (EIS) based sensing mechanisms have shown great promise, because of their high sensitivity and label-free operations. However, the method to improve EIS biosensing on μPADs is less explored. Here, we present an experimental approach to enhancing the biosensing performance of paper-based EIS nanobiosensors with working electrodes (WEs) decorated with vertically grown zinc oxide nanowires (ZnO NWs). Through a comparison among different EIS settings and an examination of ZnO-WE effects on EIS measurements, we show that Faradaic processes with Fe-based electron mediators are more reliable for ZnO-NW-enhanced working electrodes. We calibrate sensors featuring varied morphologies of ZnO NWs and achieve a low limit of detection (0.4 pg ml −1 ) for detecting p24 antigen as a marker for human immunodeficiency virus (HIV). Through theoretical analysis, imaging, and electrochemical characterizations, we reveal that the total surface area and electrochemical surface area indicate the sensitivity and sensing range of the EIS nanobiosensors. Finally, we demonstrate that the nanobiosensors are capable of differentiating the concentrations (blank, 10 ng ml −1 , 100 ng ml −1 , and 1 μg ml −1 ) of IgG antibody (CR3022) to SARS-CoV-2 in human serum samples, thus confirming the feasibility of applying the devices to COVID-19 diagnosis. This work provides a methodology that can inform the rational design of high-performance EIS-based μPADs and has the potential to facilitate rapid diagnosis in pandemics.

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