• Bergmann Weber posted an update 6 hours, 44 minutes ago

    A leading pharmacological strategy toward HIV cure requires “shock” or activation of HIV gene expression in latently infected cells with latency reversal agents (LRAs) followed by their subsequent clearance. In a screen for novel LRAs, we used fungal secondary metabolites as a source of bioactive molecules. Using orthogonal mass spectrometry (MS) coupled to latency reversal bioassays, we identified gliotoxin (GTX) as a novel LRA. GTX significantly induced HIV-1 gene expression in latent ex vivo infected primary cells and in CD4+ T cells from all aviremic HIV-1+ participants. RNA sequencing identified 7SK RNA, the scaffold of the positive transcription elongation factor b (P-TEFb) inhibitory 7SK small nuclear ribonucleoprotein (snRNP) complex, to be significantly reduced upon GTX treatment of CD4+ T cells. GTX directly disrupted 7SK snRNP by targeting La-related protein 7 (LARP7), releasing active P-TEFb, which phosphorylated RNA polymerase II (Pol II) C-terminal domain (CTD), inducing HIV transcription.Recent advances in inkjet printing of two-dimensional (2D) crystals show great promise for next-generation printed electronics development. Printing nonuniformity, however, results in poor reproducibility in device performance and remains a major impediment to their large-scale manufacturing. check details At the heart of this challenge lies the coffee-ring effect (CRE), ring-shaped nonuniform deposits formed during postdeposition drying. We present an experimental study of the drying mechanism of a binary solvent ink formulation. We show that Marangoni-enhanced spreading in this formulation inhibits contact line pinning and deforms the droplet shape to naturally suppress the capillary flows that give rise to the CRE. This general formulation supports uniform deposition of 2D crystals and their derivatives, enabling scalable and even wafer-scale device fabrication, moving them closer to industrial-level additive manufacturing.The Dzyaloshinskii-Moriya interaction (DMI) is an antisymmetric exchange interaction that stabilizes chiral spin textures. It is induced by inversion symmetry breaking in noncentrosymmetric lattices or at interfaces. Recently, interfacial DMI has been found in magnetic layers adjacent to transition metals due to the spin-orbit coupling and at interfaces with graphene due to the Rashba effect. We report direct observation of strong DMI induced by chemisorption of oxygen on a ferromagnetic layer at room temperature. The sign of this DMI and its unexpectedly large magnitude-despite the low atomic number of oxygen-are derived by examining the oxygen coverage-dependent evolution of magnetic chirality. We find that DMI at the oxygen/ferromagnet interface is comparable to those at ferromagnet/transition metal interfaces; it has enabled direct tailoring of skyrmion’s winding number at room temperature via oxygen chemisorption. This result extends the understanding of the DMI, opening up opportunities for the chemisorption-related design of spin-orbitronic devices.”Efficiency droop,” i.e., a decline in brightness of light-emitting diodes (LEDs) at high electrical currents, limits the performance of all commercial LEDs and has limited the output power of submicrometer LEDs and lasers to nanowatts. We present a fin p-n junction LED pixel that eliminates efficiency droop, allowing LED brightness to increase linearly with current. With record current densities of 1000 kA/cm2, the LEDs transition to lasing, with brightness over 20 μW. Despite a light extraction efficiency of only 15%, these devices exceed the output power of any previous electrically driven submicrometer LED or laser pixel by 100 to 1000 times while showing comparable external quantum efficiencies. Modeling suggests that spreading of the electron-hole recombination region in fin LEDs at high injection levels suppresses the nonradiative Auger recombination processes. Further refinement of this design is expected to enable a new generation of high-brightness LED and laser pixels for macro- and microscale applications.We discovered that attenuated Salmonella after intravenous injection would proliferate within various types of solid tumors but show rapid clearance in normal organs, without rendering notable toxicity. Bacteria-induced inflammation would trigger thrombosis in the infected tumors by destroying tumor blood vessels. Six types of tested tumors would all turn into darkened color with strong near-infrared absorbance, as observed by photoacoustic imaging. Under laser irradiation, those bacterial-infected tumors would be effectively ablated. Because of the immune-stimulation function, such bacteria-based photothermal therapy (PTT) would subsequently trigger antitumor immune responses, which could be further enhanced by immune checkpoint blockade to effectively suppress the growth of abscopal tumors. A robust immune memory effect to reject rechallenged tumors is also observed after bacteria-based PTT. Our work demonstrates that bacteria by themselves could act as a tumor-specific PTT agent to enable photoimmunotherapy cancer therapy to inhibit tumor metastasis and recurrence.Zebrafish faithfully regenerate their caudal fin after amputation. During this process, both differentiated cells and resident progenitors migrate to the wound site and undergo lineage-restricted, programmed cellular state transitions to populate the new regenerate. Until now, systematic characterizations of cells comprising the new regenerate and molecular definitions of their state transitions have been lacking. We hereby characterize the dynamics of gene regulatory programs during fin regeneration by creating single-cell transcriptome maps of both preinjury and regenerating fin tissues at 1/2/4 days post-amputation. We consistently identified epithelial, mesenchymal, and hematopoietic populations across all stages. We found common and cell type-specific cell cycle programs associated with proliferation. In addition to defining the processes of epithelial replenishment and mesenchymal differentiation, we also identified molecular signatures that could better distinguish epithelial and mesenchymal subpopulations in fish.