Highlights d Myeloid-specific knockout of YAP relieves inflammatory bowel disease (IBD) d YAP regulates the balance between M1 and M2 polarization d YAP expression is differentially regulated by LPS/IFN-g and IL-4/13 treatment d YAP in macrophages affects the abundance of gut microbiota in IBD mice

COVID-19 vaccines are being developed urgently worldwide. Here, we constructed two adenovirus vectored COVID-19 vaccine candidates of Sad23L-nCoV-S and Ad49L-nCoV-S carrying the full-length gene of SARS-CoV-2 spike protein. The immunogenicity of two vaccines was individually evaluated in mice. Specific immune responses were observed by priming in a dose-dependent manner, and stronger responses were obtained by boosting. Furthermore, five rhesus macaques were primed with 5×10 9 PFU Sad23L-nCoV-S, followed by boosting with 5×10 9 PFU Ad49L-nCoV-S at 4-week interval. Both mice and macaques well tolerated the vaccine inoculations without detectable clinical or pathologic changes. In macaques, prime-boost regimen induced high titers of 10 3.16 anti-S, 10 2.75 anti-RBD binding antibody and 10 2.38 pseudovirus neutralizing antibody (pNAb) at 2 months, while pNAb decreased gradually to 10 1.45 at 7 months post-priming. Robust T-cell response of IFN-γ (712.6 SFCs/10 6 cells), IL-2 (334 SFCs/10 6 cells) and intracellular IFN-γ in CD4 + /CD8 + T cell (0.39%/0.55%) to S peptides were detected in vaccinated macaques. It was concluded that prime-boost immunization with Sad23L-nCoV-S and Ad49L-nCoV-S can safely elicit strong immunity in animals in preparation of clinical phase 1/2 trials.

The Hippo pathway, which was identified from genetic screens in the fruit fly, Drosophila melanogaster, has a major size-control function in animals. All key components of the Hippo pathway, including the transcriptional coactivator Yorkie that is the most critical substrate and downstream effector of the Hippo kinase cassette, are found in the silkworm, Bombyx mori. As revealed by microarray and quantitative real-time PCR, expression of Hippo pathway genes is particularly enriched in several mitotic tissues, including the ovary, testis, and wing disc. Developmental profiles of Hippo pathway genes are generally similar (with the exception of Yorkie) within each organ, but vary greatly in different tissues showing nearly opposing expression patterns in the wing disc and the posterior silk gland (PSG) on day 2 of the prepupal stage. Importantly, the reduction of Yorkie expression by RNAi downregulated Yorkie target genes in the ovary, decreased egg number, and delayed larval-pupal-adult metamorphosis. In contrast, baculovirus-mediated YorkieCA overexpression upregulated Yorkie target genes in the PSG, increased PSG size, and accelerated larval-pupal metamorphosis. Together the results show that Yorkie potentially facilitates organ growth and metamorphosis, and suggest that the evolutionarily conserved Hippo pathway is critical for size control, particularly for PSG growth, in the silkworm.

Occult hepatitis B virus infection (OBI) carries a risk of hepatitis B virus (HBV) transmission and hepatocellular carcinoma. As previous studies have had a limited sample size, the characteristics of OBI with genotype B and C (OBI B and OBI C ) mutations relating to hepatitis B surface antibody (anti-HBs) elicited by vaccination or a limited host immune response to HBV have not been fully explored. Methods: In this study, the occurrence of OBI B or OBI C strains associated with envelope protein (pre-S/S) amino acid substitutions obtained from 99 blood donors stratified according to anti-HBs carriage were characterized extensively. Results: According to the presence of anti-HBs within each genotype, the number and frequency of substitution sites specific for anti-HBs(À) OBI B were higher than those specific for anti-HBs(+) OBI B strains (67 vs 31; 117 vs 41), but the reverse pattern was found in OBI C strains (3 vs 24; 3 vs 26). Mutations pre-s 1 T68I and sQ129R/L were found uniquely in 15-25% of anti-HBs(+) OBI B carriers and mutation pres 1 A54E was found preferentially in anti-HBs(+) OBI C , while 17 substitutions were found preferentially in 11-38% of anti-HBs(À) OBI B strains. In the major hydrophilic region (MHR) region, mutations sS167 in OBI B , sT118 in OBI C , and sA166 in both genotypes were possibly immune-induced escape mutation sites. Conclusions: Several mutations in pre-S/S of OBI appeared to be associated with carrier anti-HBs pressure, which might be risk factors for potential reactivation of viruses under anti-HBs selection in OBI carriers.

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