We present an integrated analysis of the clinical measurements, immune cells and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.

Nondestructive introduction of genes, proteins, and small molecules into mammalian cells with high efficiency is a challenging, yet critical, process. Here we demonstrate a simple nanoelectroporation platform to achieve highly efficient molecular delivery and high transfection yields with excellent uniformity and cell viability. The system is built on alumina nanostraws extending from a track-etched membrane, forming an array of hollow nanowires connected to an underlying microfluidic channel. Cellular engulfment of the nanostraws provides an intimate contact, significantly reducing the necessary electroporation voltage and increasing homogeneity over a large area. Biomolecule delivery is achieved by diffusion through the nanostraws and enhanced by electrophoresis during pulsing. The system was demonstrated to offer excellent spatial, temporal, and dose control for delivery, as well as providing high-yield cotransfection and sequential transfection.

Nanomaterials are promising candidates to improve the delivery efficiency and control of active agents such as DNA or drugs directly into cells. Here we demonstrate cell-culture platforms of nanotemplated "nanostraws" that pierce the cell membrane, providing a permanent fluidic pipeline into the cell for direct cytosolic access. Conventional polymeric track-etch cell culture membranes are alumina coated and etched to produce fields of nanostraws with controllable diameter, thickness, and height. Small molecules and ions were successfully transported into the cytosol with 40 and 70% efficiency, respectively, while GFP plasmids were successfully delivered and expressed. These platforms open the way for active, reproducible delivery of a wide variety of species into cells without endocytosis.

The epidermal growth factor receptor (EGFR) is a primary contributor to glioblastoma (GBM) initiation and progression. Here, we examine how EGFR and key downstream signaling networks contribute to the hallmark characteristics of GBM such as rapid cancer cell proliferation and diffused invasion. Additionally, we discuss current therapeutic options for GBM patients and elaborate on the mechanisms through which EGFR promotes chemoresistance. We conclude by offering a perspective on how the potential of integrative systems biology may be harnessed to develop safe and effective treatment strategies for this disease.

Direct access into cells' interiors is essential for biomolecular delivery, gene transfection, and electrical recordings yet is challenging due to the cell membrane barrier. Recently, molecular delivery using vertical nanowires (NWs) has been demonstrated for introducing biomolecules into a large number of cells in parallel. However, the microscopic understanding of how and when the nanowires penetrate cell membranes is still lacking, and the degree to which actual membrane penetration occurs is controversial. Here we present results from a mechanical continuum model of elastic cell membrane penetration through two mechanisms, namely through "impaling" as cells land onto a bed of nanowires, and through "adhesion-mediated" penetration, which occurs as cells spread on the substrate and generate adhesion force. Our results reveal that penetration is much more effective through the adhesion mechanism, with NW geometry and cell stiffness being critically important. Stiffer cells have higher penetration efficiency, but are more sensitive to NW geometry. These results provide a guide to designing nanowires for applications in cell membrane penetration.