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The first complete mitochondrial genome and phylogenetic analysis of the ornate flying snake Chrysopelea ornata (Shaw 1802) Colubridae
Enhanced energy storage performance of nano-submicron structural dielectric films by suppressed ferroelectric phase aggregation
Transcriptome‑wide excavation and expression pattern analysis of the NAC transcription factors in methyl jasmonate- and sodium chloride-induced Glycyrrhiza uralensis
Design of high-affinity binders to immune modulating receptors for cancer immunotherapy
Abstract Immune receptors have emerged as critical therapeutic targets for cancer immunotherapy. Designed protein binders can have high affinity, modularity, and stability and hence could be attractive components of protein therapeutics directed against these receptors, but traditional Rosetta based protein binder methods using small globular scaffolds have difficulty achieving high affinity on convex targets. Here we describe the development of helical concave scaffolds tailored to the convex target sites typically involved in immune receptor interactions. We employed these scaffolds to design proteins that bind to TGFβRII, CTLA-4, and PD-L1, achieving low nanomolar to picomolar affinities and potent biological activity following experimental optimization. Co-crystal structures of the TGFβRII and CTLA-4 binders in complex with their respective receptors closely match the design models. These designs should have considerable utility for downstream therapeutic applications.
Effects of different organic materials and reduced nitrogen fertilizer application on sorghum yield and soil nutrients
8q24 derived ZNF252P promotes tumorigenesis by driving phase separation to activate c-Myc mediated feedback loop
A colonic polyps detection algorithm based on an improved YOLOv5s
Retraction of “Cooperative Fe/Co-Catalyzed Remote Desaturation for the Synthesis of Unsaturated Amide Derivatives”
Measurement of interfacial thermal resistance in high-energy-density matter
Comfort, consistency, and efficiency of garments with textile electrodes versus hydrogel electrodes for neuromuscular electrical stimulation in a randomized crossover trial
Magneto-ionic vortices: voltage-reconfigurable swirling-spin analog-memory nanomagnets
Assessing the influence of olive waste on the filtration properties, elasticity, porosity, and strength of oil well cement
Author Correction: Isotopic evidence for initial coastal colonization and subsequent diversification in the human occupation of Wallacea
Early prediction of CKD from time series data using adaptive PSO optimized echo state networks
Author Correction: Atypical function of a centrosomal module in WNT signalling drives contextual cancer cell motility
Development of hypoeutectic SnBi alloy solder reinforced with WO3 nanoparticles for connecting Cu substrates via thermal bonding
CD301b+ dendritic cell-derived IL-2 dictates CD4+ T helper cell differentiation
Abstract T helper (Th) cell differentiation is fundamental to functional adaptive immunity. Different subsets of dendritic cells (DC) preferentially induce different types of Th cells, but the DC-derived mechanism for Th type 2 (Th2) differentiation is not fully understood. Here, we show that in mice, CD301b+ DCs, a major Th2-inducing DC subset, drive Th2 differentiation through cognate interaction by rapidly inducing IL-2 receptor signalling in CD4+ T cells. Mechanistically, CD40 engagement prompts IL-2 production selectively from CD301b+ DCs to maximize CD25 expression in CD4+ T cells, which instructs the Th2 fate decision, while simultaneously skewing CD4+ T cells away from the T follicular helper fate. Moreover, CD301b+ DCs utilize their own CD25 to facilitate directed action of IL-2 toward cognate CD4+ T cells, as genetic deletion of CD25 in CD301b+ DCs results in reduced IL-2-mediated signalling in antigen-specific CD4+ T cells and hence their Th2 differentiation. These results highlight the critical role of DC-intrinsic CD40–IL-2 axis in Th cell fate decision.