Direct Quantitation of SARS-CoV-2 Virus in Urban Ambient Air via a Continuous-Flow Electrochemical Bioassay.

Airborne SARS-CoV-2 virus surveillance faces challenges in complicated biomarker enrichment, interferences from various non-specific matters and extremely low viral load in the urban ambient air, leading to difficulties in detecting SARS-CoV-2 bioaerosols. This work reports a highly specific bioanalysis platform, with an exceptionally low limit-of-detection (≤1 copy m-3 ) and good analytical accordance with RT-qPCR, relying on surface-mediated electrochemical signaling and enzyme-assisted signal amplification, enabling gene and signal amplification for accurate identification and quantitation of low doses human coronavirus 229E (HCoV-229E) and SARS-CoV-2 viruses in urban ambient air. This work provides a laboratory test using cultivated coronavirus to simulate the airborne spread of SARS-CoV-2, and validate that the platform could reliably detect airborne coronavirus and reveal the transmission characteristics. This bioassay conducts the quantitation of real-world HCoV-229E and SARS-CoV-2 in airborne particulate matters collected from road-side and residential areas in Bern and Zurich (Switzerland) and Wuhan (China), with resultant concentrations verified by RT-qPCR.

Rapid and sensitive multiplex detection of COVID-19 antigens and antibody using electrochemical immunosensor-/aptasensor-enabled biochips.

We report protein- and aptamer-based electrochemical biochips for low-cost, one-step, sensitive and accurate multiplex detection of SARS-CoV-2 spike (S) and nucleocapsid (N) proteins, and IgG antibody in unprocessed clinical samples, allowing citizens to achieve rapid diagnosis at home or in community settings.

Metabolic programs tailor T cell immunity in viral infection, cancer, and aging.

Productive T cell responses to infection and cancer rely on coordinated metabolic reprogramming and epigenetic remodeling among the immune cells. In particular, T cell effector and memory differentiation, exhaustion, and senescence/aging are tightly regulated by the metabolism-epigenetics axis. In this review, we summarize recent advances of how metabolic circuits combined with epigenetic changes dictate T cell fate decisions and shape their functional states. We also discuss how the metabolic-epigenetic axis orchestrates T cell exhaustion and explore how physiological factors, such as diet, gut microbiota, and the circadian clock, are integrated in shaping T cell epigenetic modifications and functionality. Furthermore, we summarize key features of the senescent/aged T cells and discuss how to ameliorate vaccination- and COVID-induced T cell dysfunctions by metabolic modulations. An in-depth understanding of the unexplored links between cellular metabolism and epigenetic modifications in various physiological or pathological contexts has the potential to uncover novel therapeutic strategies for fine-tuning T cell immunity.

DExD/H-box helicase 9 intrinsically controls CD8+ T cell-mediated antiviral response through noncanonical mechanisms.

Upon virus infection, CD8+ T cell accumulation is tightly controlled by simultaneous proliferation and apoptosis. However, it remains unclear how TCR signal coordinates these events to achieve expansion and effector cell differentiation. We found that T cell-specific deletion of nuclear helicase Dhx9 led to impaired CD8+ T cell survival, effector differentiation, and viral clearance. Mechanistically, Dhx9 acts as the key regulator to ensure LCK- and CD3ε-mediated ZAP70 phosphorylation and ERK activation to protect CD8+ T cells from apoptosis before proliferative burst. Dhx9 directly regulates Id2 transcription to control effector CD8+ T cell differentiation. The DSRM and OB_Fold domains are required for LCK binding and Id2 transcription, respectively. Dhx9 expression is predominantly increased in effector CD8+ T cells of COVID-19 patients. Therefore, we revealed a previously unknown regulatory mechanism that Dhx9 protects activated CD8+ T cells from apoptosis and ensures effector differentiation to promote antiviral immunity independent of nuclear sensor function.