Bioorthogonal late-stage diversification of structurally complex peptides bears enormous potential for drug discovery and molecular imaging. Despite major accomplishments, these strategies heavily rely on noble-metal catalysis. Herein, we report on a manganese(I)-catalyzed peptide C─H hydroarylation that enabled the stitching of peptidic and sugar fragments, under exceedingly mild and racemization-free conditions. This convergent approach represents an atom-economical alternative to traditional iterative peptide synthesis. The robustness of the manganese(I) catalysis regime is reflected by the full tolerance of a plethora of sensitive functional groups. Our strategy enabled an expedient access to challenging cyclic peptides by a modular late-stage macrocyclization of structurally complex peptides.Swarming micro/nanorobots offer great promise in performing targeted delivery inside diverse hard-to-reach environments. However, swarm navigation in dynamic environments challenges delivery capability and real-time swarm localization. Here, we report a strategy to navigate a nanoparticle microswarm in real time under ultrasound Doppler imaging guidance for active endovascular delivery. A magnetic microswarm was formed and navigated near the boundary of vessels, where the reduced drag of blood flow and strong interactions between nanoparticles enable upstream and downstream navigation in flowing blood (mean velocity up to 40.8 mm/s). https://www.selleckchem.com/products/BI-2536.html The microswarm-induced three-dimensional blood flow enables Doppler imaging from multiple viewing configurations and real-time tracking in different environments (i.e., stagnant, flowing blood, and pulsatile flow). We also demonstrate the ultrasound Doppler-guided swarm formation and navigation in the porcine coronary artery ex vivo. Our strategy presents a promising connection between swarm control and real-time imaging of microrobotic swarms for localized delivery in dynamic environments.Fisheries in waters beyond national jurisdiction ("high seas") are difficult to monitor and manage. Their regulation for sustainability requires critical information on how fishing effort is distributed across fishing and landing areas, including possible border effects at the exclusive economic zone (EEZ) limits. We infer the global network linking harbors supporting fishing vessels to fishing areas in high seas from automatic identification system tracking data in 2014, observing a modular structure, with vessels departing from a given harbor fishing mostly in a single province. The top 16% of these harbors support 84% of fishing effort in high seas, with harbors in low- and middle-income countries ranked among the top supporters. Fishing effort concentrates along narrow strips attached to the boundaries of EEZs with productive fisheries, identifying a free-riding behavior that jeopardizes efforts by nations to sustainably manage their fisheries, perpetuating the tragedy of the commons affecting global fishery resources.CD4 T cells have been implicated in cancer immunity for their helper functions. Moreover, their direct cytotoxic potential has been shown in some patients with cancer. Here, by mining single-cell RNA-seq datasets, we identified CD4 T cell clusters displaying cytotoxic phenotypes in different human cancers, resembling CD8 T cell profiles. Using the peptide-MHCII-multimer technology, we confirmed ex vivo the presence of cytolytic tumor-specific CD4 T cells. We performed an integrated phenotypic and functional characterization of these cells, down to the single-cell level, through a high-throughput nanobiochip consisting of massive arrays of picowells and machine learning. We demonstrated a direct, contact-, and granzyme-dependent cytotoxic activity against tumors, with delayed kinetics compared to classical cytotoxic lymphocytes. Last, we found that this cytotoxic activity was in part dependent on SLAMF7. Agonistic engagement of SLAMF7 enhanced cytotoxicity of tumor-specific CD4 T cells, suggesting that targeting these cells might prove synergistic with other cancer immunotherapies.Van der Waals heterostructures consisting of graphene and transition metal dichalcogenides have shown great promise for optoelectronic applications. However, an in-depth understanding of the critical processes for device operation, namely, interfacial charge transfer (CT) and recombination, has so far remained elusive. Here, we investigate these processes in graphene-WS2 heterostructures by complementarily probing the ultrafast terahertz photoconductivity in graphene and the transient absorption dynamics in WS2 following photoexcitation. We observe that separated charges in the heterostructure following CT live extremely long beyond 1 ns, in contrast to ~1 ps charge separation reported in previous studies. This leads to efficient photogating of graphene. Furthermore, for the CT process across graphene-WS2 interfaces, we find that it occurs via photo-thermionic emission for sub-A-exciton excitations and direct hole transfer from WS2 to the valence band of graphene for above-A-exciton excitations. These findings provide insights to further optimize the performance of optoelectronic devices, in particular photodetection.The innate immune response influences neural repair after spinal cord injury (SCI). Here, we combined myeloid-specific transcriptomics and single-cell RNA sequencing to uncover not only a common core but also temporally distinct gene programs in injury-activated microglia and macrophages (IAM). Intriguingly, we detected a wide range of microglial cell states even in healthy spinal cord. Upon injury, IAM progressively acquired overall reparative, yet diversified transcriptional profiles, each comprising four transcriptional subtypes with specialized tasks. Notably, IAM have both distinct and common gene signatures as compared to neurodegeneration-associated microglia, both engaging phagocytosis, autophagy, and TyroBP pathways. We also identified an immediate response microglia subtype serving as a source population for microglial transformation and a proliferative subtype controlled by the epigenetic regulator histone deacetylase 3 (HDAC3). Together, our data unveil diversification of myeloid and glial subtypes in SCI and an extensive influence of HDAC3, which may be exploited to enhance functional recovery.