The global state of antibiotic resistance highlights the necessity for new drugs that can treat a wide range of microbial infections. Drug repurposing has several advantages, including lower costs and improved safety compared to developing a new compound. The aim of the current study is to evaluate the repurposed antimicrobial activity of Brimonidine tartrate (BT), a well-known antiglaucoma drug, and to potentiate its antimicrobial effect by using electrospun nanofibrous scaffolds. BT-loaded nanofibers were fabricated in different drug concentrations (1.5, 3, 6, and 9%) the electrospinning technique using two biopolymers (PCL and PVP). Then, the prepared nanofibers were characterized by SEM, XRD, FTIR, swelling ratio, and drug release. Afterward, the antimicrobial activities of the prepared nanofibers were investigated using different methods against several human pathogens and compared to the free BT. The results showed that all nanofibers were prepared successfully with a smooth surface. The diameters of nanofibers were reduced after loading of BT compared to the unloaded ones. In addition, scaffolds showed controlled-drug release profiles that were maintained for more than 7 days. The antimicrobial assessments revealed good activities for all scaffolds against most of the investigated human pathogens, particularly the one prepared with 9% BT which showed superiority in the antimicrobial effect over other scaffolds. To conclude, our findings proved the capability of nanofibers in loading BT and improving its repurposed antimicrobial efficacy. Therefore, it could be a promising carrier for BT to be used in combating numerous human pathogens.

Immune checkpoint therapy (ICT) has the power to eradicate cancer, but the mechanisms that determine effective therapy-induced immune responses are not fully understood. Here, using high-dimensional single-cell profiling, we interrogate whether the landscape of T cell states in the peripheral blood predict responses to combinatorial targeting of the OX40 costimulatory and PD-1 inhibitory pathways. Single-cell RNA sequencing and mass cytometry expose systemic and dynamic activation states of therapy-responsive CD4 and CD8 T cells in tumor-bearing mice with expression of distinct natural killer (NK) cell receptors, granzymes, and chemokines/chemokine receptors. Moreover, similar NK cell receptor-expressing CD8 T cells are also detected in the blood of immunotherapy-responsive cancer patients. Targeting the NK cell and chemokine receptors in tumor-bearing mice shows the functional importance of these receptors for therapy-induced anti-tumor immunity. These findings provide a better understanding of ICT and highlight the use and targeting of dynamic biomarkers on T cells to improve cancer immunotherapy.

Despite their role in host nutrition, the anaerobic gut fungal (AGF) component of the herbivorous gut microbiome remains poorly characterized. Here, to examine global patterns and determinants of AGF diversity, we generate and analyze an amplicon dataset from 661 fecal samples from 34 mammalian species, 9 families, and 6 continents. We identify 56 novel genera, greatly expanding AGF diversity beyond current estimates (31 genera and candidate genera). Community structure analysis indicates that host phylogenetic affiliation, not domestication status and biogeography, shapes the community rather than. Fungal-host associations are stronger and more specific in hindgut fermenters than in foregut fermenters. Transcriptomics-enabled phylogenomic and molecular clock analyses of 52 strains from 14 genera indicate that most genera with preferences for hindgut hosts evolved earlier (44-58 Mya) than those with preferences for foregut hosts (22-32 Mya). Our results greatly expand the documented scope of AGF diversity and provide an ecologically and evolutionary-grounded model to explain the observed patterns of AGF diversity in extant animal hosts.

Four concentrations of Klucel E and cellulose nanofiber (CNF) nanocomposite were prepared by adding 10, 20, 30, and 50 ml of 2% (wt./v) CNF to 3% (wt./v) of Klucel E to obtain a 100 ml. final volume of the composite. The composites were characterized using transmission electron microscopy (TEM), scan- ning electron microscopy (SEM), and X-ray diffraction (XRD). The addition of CNF to Klucel E improved the mechanical properties of the prepared composites; namely the composite which contains 50% CNF showed an improvement in tensile strength by 102% compared to pure Klucel E. Additionally, Young’s modulus, and hardness increased dramatically with the increase of CNF within the composite. To fur- ther evaluate the nanocomposites, CNF 30% and CNF 50%, were used to treat aged wood specimens. The compression strength of the untreated and treated specimen was measured, where the sample treated with Klucel E/30% CNF composite showed the highest compression strength value with an improvement of 14.5% compared to the untreated wood sample.

With the advent of multiplex fluorescence in situ hybridization (FISH) and in situ RNA sequencing technologies, spatial transcriptomics analysis is advancing rapidly, providing spatial location and gene expression information about cells in tissue sections at single cell resolution. Cell type classification of these spatially-resolved cells can be inferred by matching the spatial transcriptomics data to reference atlases derived from single cell RNA-sequencing (scRNA-seq) in which cell types are defined by differences in their gene expression profiles. However, robust cell type matching of the spatially-resolved cells to reference scRNA-seq atlases is challenging due to the intrinsic differences in resolution between the spatial and scRNA-seq data. In this study, we systematically evaluated six computational algorithms for cell type matching across four image-based spatial transcriptomics experimental protocols (MERFISH, smFISH, BaristaSeq, and ExSeq) conducted on the same mouse primary visual cortex (VISp) brain region. We find that many cells are assigned as the same type by multiple cell type matching algorithms and are present in spatial patterns previously reported from scRNA-seq studies in VISp. Furthermore, by combining the results of individual matching strategies into consensus cell type assignments, we see even greater alignment with biological expectations. We present two ensemble meta-analysis strategies used in this study and share the consensus cell type matching results in the Cytosplore Viewer ( https://viewer.cytosplore.org ) for interactive visualization and data exploration. The consensus matching can also guide spatial data analysis using SSAM, allowing segmentation-free cell type assignment.