Cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA during virus infection and induces an antiviral state. cGAS signals by synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING). We show that cGAMP is incorporated into viral particles, including lentivirus and herpesvirus virions, when these are produced in cGAS-expressing cells. Virions transferred cGAMP to newly infected cells and triggered a STING-dependent antiviral program. These effects were independent of exosomes and viral nucleic acids. Our results reveal a way by which a signal for innate immunity is transferred between cells, potentially accelerating and broadening antiviral responses. Moreover, infection of dendritic cells with cGAMP-loaded lentiviruses enhanced their activation. Loading viral vectors with cGAMP therefore holds promise for vaccine development.
Complex biological processes such as plant growth and development are often under the control of transcription factors that regulate the expression of large sets of genes and activate subordinate transcription factors in a cascade-like fashion. Here, by screening candidate photosynthesis-related transcription factors in rice, we identified a DREB (Dehydration Responsive Element Binding) family member, OsDREB1C, in which expression is induced by both light and low nitrogen status. We show that OsDREB1C drives functionally diverse transcriptional programs determining photosynthetic capacity, nitrogen utilization, and flowering time. Field trials with
OsDREB1C
-overexpressing rice revealed yield increases of 41.3 to 68.3% and, in addition, shortened growth duration, improved nitrogen use efficiency, and promoted efficient resource allocation, thus providing a strategy toward achieving much-needed increases in agricultural productivity.
Highly
infiltrative and invasive glioma cells obscure the boundary
between tumor and normal brain tissue, making it extremely difficult
to precisely diagnose and completely remove. The combination of multimodal
imaging with effective treatments to diagnose precisely and guide
surgery and therapy accurately is desperately needed for glioma in
the brain. Here, we report a biomimetic catalase-integrated-albumin
phototheranostic nanoprobe (ICG/AuNR@BCNP) to realize multimodal imaging,
amplify phototherapy, and guide surgery for glioma after penetrating
the blood–brain barrier, accumulating into deep-seated glioma via albumin-binding protein mediated transportation. The
phototheranostic nanoprobe enabled fluorescence, photoacoustic, and
infrared thermal imaging with desirable detecting depth and high signal-to-background
ratio for clearly differentiating brain tumors from surrounding tissues.
Meanwhile, the nanoprobe could effectively induce local hyperthermia
and promote the level of singlet oxygen based on alleviated hypoxic
glioma microenvironment by decomposing endogenous hydrogen peroxide
to oxygen to amplify phototherapy. Thus, significant inhibition of
glioma growth, extended survival time, alleviated tumor hypoxia, improved
apoptosis, and antiangiogenesis effects were exhibited in several
animal models including the periphery and the brain through intravenous
or intratumoral injection, meanwhile with low toxicity to normal tissue.
The phototherapy was also guided by the assistance of external bioluminescence,
magnetic resonance, and positron emission tomography imaging. Moreover,
the nanoprobe could accurately guide the glioma resection. These results
suggest that the phototheranostic nanoprobe is a promising nanoplatform
specifically for glioma to achieve multimodal diagnosis, effective
phototherapy, and accurate imaging-guided surgery.
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