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The interaction between foot-and-mouth disease virus (FMDV) and the host is extremely important for virus infection, but there are few researches on it, which is not conducive to vaccine development and FMD control. In this study, we designed a porcine genome-scale CRISPR/Cas9 knockout library containing 93,859 single guide RNAs targeting 16,886 protein-coding genes, 25 long ncRNAs, and 463 microRNAs. Using this library, several previously unreported genes required for FMDV infection are highly enriched post-FMDV selection in IBRS-2 cells. Follow-up studies confirmed the dependency of FMDV on these genes, and we identified a functional role for one of the FMDV-related host genes: TOB1 (Transducer of ERBB2.1). TOB1-knockout significantly inhibits FMDV infection by positively regulating the expression of RIG-I and MDA5. We further found that TOB1-knockout led to more accumulation of mRNA transcripts of transcription factor CEBPA, and thus its protein, which further enhanced transcription of RIG-I and MDA5 genes. In addition, TOB1-knockout was shown to inhibit FMDV adsorption and internalization mediated by EGFR/ERBB2 pathway. Finally, the FMDV lethal challenge on TOB1-knockout mice confirmed that the deletion of TOB1 inhibited FMDV infection in vivo. These results identify TOB1 as a key host factor involved in FMDV infection in pigs. Author summary: Host factors play a critical role in FMDV infection, however, the mechanisms are poorly understood. Aiming to comprehensively study the host factors involved in FMDV infection, we develop a porcine genome-scale CRISPR/Cas9 knockout library and successfully confirmed that the knockout of TOB1 (Transducer of ERBB2.1) could significantly inhibit FMDV infection. On one hand, TOB1-knockout could promote the expression of RIG-I and MDA5, and thus IFNB and ISGs (interferon stimulating genes), thereby inhibiting FMDV infection. On the other hand, TOB1-knockout inhibits FMDV entry mediated by EGFR/ERBB2 pathway. These findings reveal TOB1 as a key host factor mediating FMDV infection in pigs. [ABSTRACT FROM AUTHOR]

Recently, a G-protein coupled receptor 44 (GPR44) was discovered to play a significant role in the process of inflammation-related diseases, including cancer and diabetes. However, the precise role of GPR44 has yet to be fully elucidated. Currently, there is a strong and urgent need for the development of GPR44 radiotracers as a non-invasive methodology to explore the exact mechanism of GPR44 on inflammation-related diseases and monitor the progress of therapy. TM-30089 is a potent GPR44 antagonist that exhibits a high specificity and selectivity for GPR44. Its structure contains a fluorine nuclide, which could potentially be replaced with 18F. In the present study, we successfully took a highly effective synthesis strategy that pretreated the unprotected carboxylic acid group of the precursor and developed a feasible one-step automatic radiosynthesis strategy for [18F]TM-30089 with a high radiochemical purity and a good radiochemical yield. We further evaluated this radiotracer using mice models implanted with 1.1 B4 cell lines (GPR44-enriched cell lines) and human islets (high GPR44 expression), respectively. The results revealed the persistent and specific uptake of [18F]TM-30089 in GPR44 region, indicating that [18F]TM-30089 is a promising candidate for targeting GPR44. Further evaluation is ongoing. [ABSTRACT FROM AUTHOR]

The world-wide high incidence of non-alcoholic fatty liver disease (NAFLD) is of concern for its progression to insulin resistance, steatohepatitis and cardiovascular disease (CVD). The increased uptake of fatty acids in critical organs plays a major role in NAFLD progression. Male Ceacam1−/− mice that develop NAFLD, insulin resistance and CVD on normal chow are a potential model for studying the dysregulation of fatty acid uptake. [18F]fluoro-4-thia-oleate ([18F]FTO) was chosen as a fatty acid reporter because of its higher uptake and retention in the heart in an animal model of CVD. Male wild-type (WT) or Ceacam1−/− mice fasted 4–6 h were administered [18F]FTO i.v., and dynamic PET scans were conducted in an MR/PET small animal imaging system along with terminal tissue biodistributions. Quantitative heart image analysis revealed significantly higher uptake at 35 min in Ceacam1−/− (6.0 ± 1.0% ID/cc) vs. WT (3.9 ± 0.6% ID/cc) mice (p = 0.006). Ex vivo heart uptake/retention (% ID/organ) was 2.82 ± 0.45 for Ceacam1−/− mice vs. 1.66 ± 0.45 for WT mice (p < 0.01). Higher kidney and pancreas uptake/retention in Ceacam1−/− was also evident, and the excretion of [18F]FTO into the duodenum was observed for both WT and Ceacam1−/− mice starting at 10 min. This study suggests that the administration of [18F]FTO as a marker of fatty acid uptake and retention may be an important tool in analyzing the effect of NAFLD on lipid dysregulation in the heart. [ABSTRACT FROM AUTHOR]

A simpleand efficient method for the synthesis of β-aminoacryaldehydesvia Cu(OAc)2·H2O and FeCl3cocatalyzedMeyer–Schuster-Like rearrangement of propargylic amines wasdeveloped. The reactions proceed selectively as the E-isomers in generally good yields under aerobic conditions, and arecompatible with a broad range of functional groups. This method combinesC–N bond cleavage as well as the N-aryl groupmigration and provides a practical and mild synthetic approach toα,β-unsaturated carbonyl compounds, which are useful precursorsin a variety of functional group transformations. [ABSTRACT FROM AUTHOR]

A copper-catalyzed C–H amidationprocess, with azides as amino sources under oxidant-free conditions,has been developed. When N-heterocycles were employedas directing groups, sulfonylazide and benzoylazide could be usedas amidating reagents to provide corresponding N-arylamides.When amidines or imine were used, tandem C–N/N–N bondformation occurred to afford indazole derivatives in one pot. [ABSTRACT FROM AUTHOR]

An unprecedented palladium-catalyzed cyanation of aromatic C–H bonds by using tertiary amine derived isocyanide as a novel cyano source was developed. Cu(TFA)2was used as a requisite stoichiometric oxidant. Mechanistic studies suggest that a tertiary carbon cation-based intermediate is involved following the C–N bond breakage. [ABSTRACT FROM AUTHOR]

An efficient synthesis of free (NH)-phenanthridinones through Pd-catalyzed C(sp2)–H aminocarbonylation of unprotected o-arylanilines under an atmospheric pressure of CO has been developed. Some ortho heteroarene substituted anilines as well as N-alkyl protected o-arylanilines are also suitable substrates for this C–H aminocarbonylation reaction. [ABSTRACT FROM AUTHOR]

A synthesis of imidazo[1,5-a]pyridines through a three-component reaction involving benzyl substituted pyridines, aldehydes, and TMSN3 is developed. [ABSTRACT FROM AUTHOR]

The article presents chemical equations related to the article "Copper-Catalyzed C(sp²)--H Amidation with Azides as Amino Sources" by J. Peng and others, published in the periodical "Organic Letters" in 2014.

Mechanistic studies indicate a tertiary carbon cation to be an intermediate. [ABSTRACT FROM AUTHOR]