Baligang is a Neolithic site on a northern tributary of the middle Yangtze and provides a long archaeobotanical sequence from the Seventh Millennium BC upto the First Millennium BC. It provides evidence for developments in rice and millet agriculture influenced by shifting cultural affiliation with the north (Yangshao and Longshan) and south (Qujialing and Shijiahe) between 4300 and 1800 BC. This paper reports on plant macro-remains (seeds), from systematic flotation of 123 samples (1700 litres), producing more than 10,000 identifiable remains. The earliest Pre-Yangshao occupation of the sites provide evidence for cultivation of rice (Oryza sativa) between 6300–6700 BC. This rice appears already domesticated in on the basis of a dominance of non-shattering spikelet bases. However, in terms of grain size changes has not yet finished, as grains are still thinner than more recent domesaticated rice and are closer in grain shape to wild rices. This early rice was cultivated alongside collection of wild staple foods, especially acorns (Quercus/Lithicarpus sensu lato). In later periods the sites has evidence for mixed farming of both rice and millets (Setaria italica and Panicum miliaceum). Soybean appears on the site in the Shijiahe period (ca.2500 BC) and wheat (Triticum cf. aestivum) in the Late Longshan levels (2200–1800 BC). Weed flora suggests an intensification of rice agriculture over time with increasing evidence of wetland weeds. We interpret these data as indicating early opportunistic cultivation of alluvial floodplains and some rainfed rice, developing into more systematic and probably irrigated cultivation starting in the Yangshao period, which intensified in the Qujialing and Shijiahe period, before a shift back to an emphasis on millets with the Late Longshan cultural influence from the north.

Bats harbor severe acute respiratory syndrome (SARS)-like coronaviruses (SL-CoVs) from which the causative agent of the 2002-2003SARS pandemic is thought to have originated. However, despite the fact that a large number of genetically diverse SL-CoV sequences have been detected in bats, only two strains (named WIV1 and WIV16) have been successfully cultured in vitro. These two strains differ from SARS-CoV only in containing an extra open reading frame (ORF) (named ORFX), between ORF6 and ORF7, which has no homology to any known protein sequences. In this study, we constructed a full-length cDNA clone of SL-CoV WIV1 (rWIV1), an ORFX deletion mutant (rWIV1-⌬X), and a green fluorescent protein (GFP)-expressing mutant (rWIV1-GFP-⌬X). Northern blotting and fluorescence microscopy indicate that ORFX was expressed during WIV1 infection. A virus infection assay showed that rWIV1-⌬X replicated as efficiently as rWIV1 in Vero E6, Calu-3, and HeLa-hACE2 cells. Further study showed that ORFX could inhibit interferon production and activate NF-B. Our results demonstrate for the first time that the unique ORFX in the WIV1 strain is a functional gene involving modulation of the host immune response but is not essential for in vitro viral replication. IMPORTANCE Bats harbor genetically diverse SARS-like coronaviruses (SL-CoVs), and some of them have the potential for interspecies transmission. A unique open reading frame (ORFX) was identified in the genomes of two recently isolated bat SL-CoV strains (WIV1 and -16). It will therefore be critical to clarify whether and how this protein contributes to virulence during viral infection.Here we revealed that the unique ORFX is a functional gene that is involved in the modulation of the host immune response but is not essential for in vitro viral replication. Our results provide important information for further exploration of the ORFX function in the future. Moreover, the reverse genetics system we constructed will be helpful for study of the pathogenesis of this group of viruses and to develop therapeutics for future control of emerging SARS-like infections. Severe acute respiratory syndrome coronavirus (SARS-CoV) is a zoonotic pathogen that caused the 2002-2003 SARS pandemic, which originated in China (1). Since then, genetically diverse SARS-like coronaviruses (SL-CoVs) have been reported in bats in China, Europe, and Africa (2-11), indicating a wide geographic distribution of this group of viruses. However, most bat SL-CoVs have been identified only by sequences and are not fully characterized due to the lack of cultured viruses. Thus, their potential for transmission to and likely pathogenesis in domestic animals and humans remain untested. WIV1 and WIV16 are two recently identified SL-CoV strains with high genomic similarity to human SARS-CoV. These two strains have been successfully cultured in vitro and have been shown to use the same molecule (angiotensin-converting enzyme [ACE2]) for cellular entry as SARS-CoV (2, 10). Recently, another bat SL-CoV strain, SHC014, ...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19.