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Self-reactive CD8+ T cells are important mediators of progressive tissue damage in autoimmune diseases, but the molecular program underlying these cells' functional adaptation is unclear. Here we characterize the transcriptional and epigenetic landscape of self-reactive CD8+ T cells in a mouse model of protracted central nervous system (CNS) autoimmunity and compare it to populations of CNS-resident memory CD8+ T cells emerging from acute viral infection. We find that autoimmune CD8+ T cells persisting at sites of self-antigen exhibit characteristic transcriptional regulation together with distinct epigenetic remodeling. This self-reactive CD8+ T cell fate depends on the transcriptional regulation by the DNA-binding HMG-box protein TOX which remodels more than 400 genomic regions including loci such as Tcf7, which is central to stemness of CD8+ T cells. Continuous exposure to CNS self-antigen sustains TOX levels in self-reactive CD8+ T cells, whereas genetic ablation of TOX in CD8+ T cells results in shortened persistence of self-reactive CD8+ T cells in the inflamed CNS. Our study establishes and characterizes the genetic differentiation program enabling chronic T cell-driven immunopathology in CNS autoimmunity.Stringent nonpharmaceutical interventions (NPIs) such as lockdowns and border closures are not currently recommended for pandemic influenza control. New Zealand used these NPIs to eliminate coronavirus disease 2019 during its first wave. Using multiple surveillance systems, we observed a parallel and unprecedented reduction of influenza and other respiratory viral infections in 2020. This finding supports the use of these NPIs for controlling pandemic influenza and other severe respiratory viral threats.Electrochromic devices can modulate their light absorption under a small driving voltage, but the requirement for external electrical supplies causes response-lag. To address this problem, self-powered electrochromic devices have been studied recently. However, insensitivity to the surrounding light and unsatisfactory stability of electrochromic devices have hindered their critical applications. Herein, novel perovskite solar cell-powered all-in-one gel electrochromic devices have been assembled and studied in order to achieve automatic light adjustment. Two alkynyl-containing viologen derivatives are synthesized as electrochromic materials, the devices with very high stability (up to 70000 cycles) serves as the energy storage and smart window, while the perovskite solar cell with power-conversion-efficiency up to 18.3% serves as the light detector and power harvester. The combined devices can automatically switch between bleached and colored state to adjust light absorption with variable surrounding light intensity in real-time swiftly, which establish significant potentials for applications as modern all-day intelligent windows.Semiconductors have long been perceived as a prerequisite for solid-state transistors. Although switching principles for nanometer-scale devices have emerged based on the deployment of two-dimensional (2D) van der Waals heterostructures, tunneling and ballistic currents through short channels are difficult to control, and semiconducting channel materials remain indispensable for practical switching. In this study, we report a semiconductor-less solid-state electronic device that exhibits an industry-applicable switching of the ballistic current. This device modulates the field emission barrier height across the graphene-hexagonal boron nitride interface with ION/IOFF of 106 obtained from the transfer curves and adjustable intrinsic gain up to 4, and exhibits unprecedented current stability in temperature range of 15-400 K. check details The vertical device operation can be optimized with the capacitive coupling in the device geometry. The semiconductor-less switching resolves the long-standing issue of temperature-dependent device performance, thereby extending the potential of 2D van der Waals devices to applications in extreme environments.Improved methods for malaria diagnosis are urgently needed. Here, we evaluate a novel method named rotating-crystal magneto-optical detection (RMOD) in 956 suspected malaria patients in Papua New Guinea. RMOD tests can be conducted within minutes and at low cost. We systematically evaluate the capability of RMOD to detect infections by directly comparing it with expert light microscopy, rapid diagnostic tests and polymerase chain reaction on capillary blood samples. We show that compared to light microscopy, RMOD exhibits 82% sensitivity and 84% specificity to detect any malaria infection and 87% sensitivity and 88% specificity to detect Plasmodium vivax. This indicates that RMOD could be useful in P. vivax dominated elimination settings. Parasite density correlates well with the quantitative magneto-optical signal. Importantly, residual hemozoin present in malaria-negative patients is also detectable by RMOD, indicating its ability to detect previous infections. This could be exploited to reveal transmission hotspots in low-transmission settings.Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in the live mouse brain, differential therapeutic responses in both niches are determined. Both the PVN, a preferential location of long-term quiescent glioma cells, and network integration facilitate resistance against cytotoxic effects of radiotherapy and chemotherapy-independently of each other, but with additive effects. Perivascular glioblastoma cells are particularly able to actively repair damage to tumor regions. Population of the PVN and resistance in it depend on proficient NOTCH1 expression. In turn, NOTCH1 downregulation induces resistant multicellular networks by TM extension. Our findings identify NOTCH1 as a central switch between the PVN and network niche in glioma, and demonstrate robust cross-compensation when only one niche is targeted.
Homepage: https://www.selleckchem.com/products/ldc203974-imt1b.html
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