This study identifies mechanisms mediating responses to immune checkpoint inhibitors using mouse models of triple-negative breast cancer. By creating new mammary tumor models, we find that tumor mutation burden and specific immune cells are associated with response. Further, we developed a rich resource of single-cell RNA-seq and bulk mRNA-seq data of immunotherapy-treated and non-treated tumors from sensitive and resistant murine models. Using this, we uncover that immune checkpoint therapy induces T follicular helper cell activation of B cells to facilitate the anti-tumor response in these models. We also show that B cell activation of T cells and the generation of antibody are key to immunotherapy response and propose a new biomarker for immune checkpoint therapy. In total, this work presents resources of new preclinical models of breast cancer with large mRNA-seq and single-cell RNA-seq datasets annotated for sensitivity to therapy and uncovers new components of response to immune checkpoint inhibitors.

The use of conductive polymer composites (CPCs) as strain sensors has been widely investigated and various resistivity-strain sensitivities are desirable for different applications. In this study, the use of mixed carbon fillers and functionalized carbon nanotubes was demonstrated to be vital for preparing thermoplastic polyurethane (TPU)-based strain sensors with tunable sensitivity. To understand the strain sensing behavior, we carried out scanning electron microscopy (SEM), Raman spectroscopy, wide-angle X-ray diffraction (WAXD), mechanical test, and rheology-electrical measurement. Hybrid fillers of multi-walled carbon nanotubes (MWNTs) and carbon black (CB) could reduce the entanglement in conductive network structure, thus increase the resistivity-strain sensitivity. Furthermore, incorporation of additional functionalized MWNTs in the CPCs could enhance the interfacial interaction between nanofillers and TPU, leading to further increase in sensitivity. Through such a simple method, strain sensors could be efficiently fabricated with large strain-sensing capability (strain as large as 200%) and a wide range of strain sensitivity (gauge factor ranging from 5 to 140238). Finally, the exponential revolution of resistive response to strain was fitted with a model based on tunneling theory by Simmons. It was observed that the change in tunneling distance and the number of conductive pathways could be accelerated significantly by adjusting conductive network structure and interfacial interaction. This study provides a guideline for the preparation of high-performance CPC strain sensors with a large range of resistivity-strain sensitivity.

Miscanthus is a perennial wild grass that is of global importance for paper production, roofing, horticultural plantings, and an emerging highly productive temperate biomass crop. We report a chromosome-scale assembly of the paleotetraploid M. sinensis genome, providing a resource for Miscanthus that links its chromosomes to the related diploid Sorghum and complex polyploid sugarcanes. The asymmetric distribution of transposons across the two homoeologous subgenomes proves Miscanthus paleo-allotetraploidy and identifies several balanced reciprocal homoeologous exchanges. Analysis of M. sinensis and M. sacchariflorus populations demonstrates extensive interspecific admixture and hybridization, and documents the origin of the highly productive triploid bioenergy crop M. × giganteus. Transcriptional profiling of leaves, stem, and rhizomes over growing seasons provides insight into rhizome development and nutrient recycling, processes critical for sustainable biomass accumulation in a perennial temperate grass. The Miscanthus genome expands the power of comparative genomics to understand traits of importance to Andropogoneae grasses.

Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 is a virus-induced inflammatory disease of the airways and lungs that leads to severe multi-organ damage and death. Here we show that cellular lipid synthesis is required for SARS-CoV-2 replication and offers an opportunity for pharmacological intervention. Screening a short-hairpin RNA sublibrary that targets metabolic genes, we identified genes that either inhibit or promote SARS-CoV-2 viral infection, including two key candidate genes, ACACA and FASN , which operate in the same lipid synthesis pathway. We further screened and identified several potent inhibitors of fatty acid synthase (encoded by FASN ), including the US Food and Drug Administration-approved anti-obesity drug orlistat, and found that it inhibits in vitro replication of SARS-CoV-2 variants, including more contagious new variants, such as Delta. In a mouse model of SARS-CoV-2 infection (K18-hACE2 transgenic mice), injections of orlistat resulted in lower SARS-CoV-2 viral levels in the lung, reduced lung pathology and increased mouse survival. Our findings identify fatty acid synthase inhibitors as drug candidates for the prevention and treatment of COVID-19 by inhibiting SARS-CoV-2 replication. Clinical trials are needed to evaluate the efficacy of repurposing fatty acid synthase inhibitors for severe COVID-19 in humans.