BackgroundNo clinically proven effective antiviral strategy exists for the epidemic Coronavirus Disease 2019 . MethodsWe conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Patients were randomly assigned in a 1:1 ratio to receive conventional therapy plus Umifenovir (Arbidol) (200mg*3/day) or Favipiravir (1600mg*2/first day followed by 600mg*2/day) for 10 days. The primary outcome was clinical recovery rate of Day 7. Latency to relief for pyrexia and cough, the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV) were the secondary outcomes. Safety data were collected for 17 days.

Cryptochromes (CRYs) are blue-light photoreceptors that mediate various light responses in plants and animals. The signaling mechanism by which CRYs regulate light responses involves their physical interactions with COP1. Here, we report that CRY1 interacts physically with SPA1 in a blue-light-dependent manner. SPA acts genetically downstream from CRYs to regulate light-controlled development. Blue-light activation of CRY1 attenuates the association of COP1 with SPA1 in both yeast and plant cells. These results indicate that the blue-light-triggered CRY1-SPA1 interaction may negatively regulate COP1, at least in part, by promoting the dissociation of COP1 from SPA1. This interaction and consequent dissociation define a dynamic photosensory signaling mechanism.

Nanomaterials are at the leading edge of the emerging field of nanotechnology. Their unique and tunable size-dependent properties (in the range 1-100 nm) make these materials indispensable in many modern technological applications. In this Review, we summarize the state-of-art in the manufacture and applications of inorganic nanoparticles made using continuous hydrothermal flow synthesis (CHFS) processes. First, we introduce ideal requirements of any flow process for nanoceramics production, outline different approaches to CHFS, and introduce the pertinent properties of supercritical water and issues around mixing in flow, to generate nanoparticles. This Review then gives comprehensive coverage of the current application space for CHFS-made nanomaterials including optical, healthcare, electronics (including sensors, information, and communication technologies), catalysis, devices (including energy harvesting/conversion/fuels), and energy storage applications. Thereafter, topics of precursor chemistry and products, as well as materials or structures, are discussed (surface-functionalized hybrids, nanocomposites, nanograined coatings and monoliths, and metal-organic frameworks). Later, this Review focuses on some of the key apparatus innovations in the field, such as in situ flow/rapid heating systems (to investigate kinetics and mechanisms), approaches to high throughput flow syntheses (for nanomaterials discovery), as well as recent developments in scale-up of hydrothermal flow processes. Finally, this Review covers environmental considerations, future directions and capabilities, along with the conclusions and outlook.

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Direct injection of cell-laden hydrogels shows high potential for tissue regeneration in translational therapy. The traditional cell-laden hydrogels are often used as bulk space fillers to tissue defects after injection, likely limiting their structural controllability. On the other hand, patterned cell-laden hydrogel constructs often necessitate invasive surgical procedures. To overcome these problems, herein, a unique strategy is reported for encapsulating living human cells in a pore-forming gelatin methacryloyl (GelMA)-based bioink to ultimately produce injectable hierarchically macro-micro-nanoporous cellladen GelMA hydrogel constructs through 3D extrusion bioprinting. The hydrogel constructs can be fabricated into various shapes and sizes that are defect-specific. Due to the hierarchically macro-micro-nanoporous structures, the cell-laden hydrogel constructs can readily recover to their original shapes, and sustain high cell viability, proliferation, spreading, and differentiation after compression and injection. In addition, in vivo studies further reveal that the hydrogel constructs can integrate well with the surrounding host tissues. These findings suggest that the unique 3D-bioprinted pore-forming GelMA hydrogel constructs are promising candidates for applications in minimally invasive tissue regeneration and cell therapy.