All metazoan guts are in permanent contact with the microbial realm. However, understanding of the exact mechanisms by which the strength of gut immune responses is regulated to achieve gut-microbe mutualism is far from complete. Here we identify a signaling network composed of complex positive and negative mechanisms that controlled the expression and activity of dual oxidase (DUOX), which 'fine tuned' the production of microbicidal reactive oxygen species depending on whether the gut encountered infectious or commensal microbes. Genetic analyses demonstrated that negative and positive regulation of DUOX was required for normal host survival in response to colonization with commensal and infectious microbes, respectively. Thus, the coordinated regulation of DUOX enables the host to achieve gut-microbe homeostasis by efficiently combating infection while tolerating commensal microbes.
An emerging electronic material as one of transition metal dichalcogenides (TMDCs), tungsten disulfide (WS2) can be exfoliated as an atomically thin layer and can compensate for the drawback of graphene originating from a gapless band structure. A direct bandgap, which is obtainable in single-layer WS2, is an attractive characteristic for developing optoelectronic devices, as well as field-effect transistors. However, its relatively low mobility and electrical characteristics susceptible to environments remain obstacles for the use of device materials. Here, we demonstrate remarkable improvement in the electrical characteristics of single-layer WS2 field-effect transistor (SL-WS2 FET) using chemical vapor deposition (CVD)-grown hexagonal BN (h-BN). SL-WS2 FET sandwiched between CVD-grown h-BN films shows unprecedented high mobility of 214 cm2/Vs at room temperature. The mobility of a SL-WS2 FET has been found to be 486 cm2/Vs at 5 K. The ON/OFF ratio of output current is ~107 at room temperature. Apart from an ideal substrate for WS2 FET, CVD-grown h-BN film also provides a protection layer against unwanted influence by gas environments. The h-BN/SL-WS2/h-BN sandwich structure offers a way to develop high-quality durable single-layer TMDCs electronic devices.
Ionizable lipid nanoparticles (LNPs) have been widely used for in vivo delivery of RNA therapeutics into the liver. However, a main challenge remains to develop LNP formulations for selective delivery of RNA into certain types of liver cells, such as hepatocytes and liver sinusoidal endothelial cells (LSECs). Here, we report the engineered LNPs for the targeted delivery of RNA into hepatocytes and LSECs. The effects of particle size and polyethylene glycol–lipid content in the LNPs were evaluated for the hepatocyte-specific delivery of mRNA by ApoE-mediated cellular uptake through low-density lipoprotein receptors. Targeted delivery of RNA to LSECs was further investigated using active ligands. Incorporation of mannose allowed the selective delivery of RNA to LSECs, while minimizing the unwanted cellular uptake by hepatocytes. These results demonstrate that engineered LNPs have great potential for the cell type–specific delivery of RNA into the liver and other tissues.
A specific and sensitive fluorescence-based method was developed for the imaging of microbe-induced HOCl production. Furthermore, we demonstrate dual oxidase (DUOX)-mediated HOCl generation in the mucosa of live animals providing a novel insight into mucosal innate immunity.
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