HR121 targeting HR2 domain in S2 subunit of spike protein can serve as a broad-spectrum SARS-CoV-2 inhibitor via intranasal administration.

The continuously emerging SARS-CoV-2 variants pose a great challenge to the efficacy of current drugs, this necessitates the development of broad-spectrum antiviral drugs. In the previous study, we designed a recombinant protein, heptad repeat (HR) 121, as a variant-proof vaccine. Here, we found it can act as a fusion inhibitor and demonstrated broadly neutralizing activities against SARS-CoV-2 and its main variants. Structure analysis suggested that HR121 targets the HR2 domain in SARS-CoV-2 spike (S) 2 subunit to block virus-cell fusion. Functional experiments demonstrated that HR121 can bind HR2 at serological-pH and endosomal-pH, highlighting its inhibition capacity when SARS-CoV-2 enters via either cellular membrane fusion or endosomal route. Importantly, HR121 can effectively inhibit SARS-CoV-2 and Omicron variant pseudoviruses entering the cells, as well as block authentic SARS-CoV-2 and Omicron BA.2 replications in human pulmonary alveolar epithelial cells. After intranasal administration to Syrian golden hamsters, it can protect hamsters from SARS-CoV-2 and Omicron BA.2 infection. Together, our results suggest that HR121 is a potent drug candidate with broadly neutralizing activities against SARS-CoV-2 and its variants.

Who's Next: Rising Star Prediction via Diffusion of User Interest in Social Networks

Finding items with potential to increase sales is of great importance in online market. In this paper, we propose to study this novel and practical problem: rising star prediction. We call these potential items Rising Star , which implies their ability to rise from low-turnover items to best-sellers in the future. Rising stars can be used to help with unfair recommendation in e-commerce platform, balance supply and demand to benefit the retailers and allocate marketing resources rationally. Although the study of rising star can bring great benefits, it also poses challenges to us. The sales trend of rising star fluctuates sharply in the short-term and exhibits more contingency caused by some external events (e.g., COVID-19 caused increasing purchase of the face mask) than other items, which cannot be solved by existing sales prediction methods. To address above challenges, in this paper, we observe that the presence of rising stars is closely correlated with the early diffusion of user interest in social networks, which is validated in the case of Taocode (an intermediary that diffuses user interest in Taobao). Thus, we propose a novel framework, RiseNet, to incorporate the user interest diffusion process with the item dynamic features to effectively predict rising stars. Specifically, we adopt a coupled mechanism to capture the dynamic interplay between items and user interest, and a special designed GNN based framework to quantify user interest. Our experimental results on large-scale real-world datasets provided by Taobao demonstrate the effectiveness of our proposed framework.

Significant neutralizing escapes of Omicron and its sublineages in SARS-CoV-2-infected individuals vaccinated with inactivated vaccines.

In China, most SARS-CoV-2-infected individuals had been vaccinated with inactivated vaccines. However, little is known about their immune resistances to the previous variants of concerns (VOCs) and the current Omicron sublineages. Here, we collected convalescent serum samples from SARS-CoV-2-infected individuals during the ancestral, Delta, and Omicron BA.1 waves, and evaluated their cross-neutralizing antibodies (nAbs) against the previous VOCs and the current Omicron sublineages using VSV-based pseudoviruses. In the convalescents who had been unvaccinated and vaccinated with two doses of inactivated vaccines, we found infections from either the ancestral or the Delta strain elicited moderate cross-nAbs to previous VOCs, but very few cross-nAbs to the Omicron sublineages, including BA.1, BA.2, BA.3, and BA.4/5. The individuals who had been vaccinated with two doses of inactivated vaccines before Omicron BA.1 infection had moderate nAbs to Omicron BA.1, but weak cross-nAbs to the other Omicron sublineages. While three doses of inactivated vaccines followed Omicron BA.1 infection induced elevated and still weak cross-nAbs to other Omicron sublineages. Our results indicate that the Omicron sublineages show significant immune escape in the previously SARS-CoV-2-infected individuals and thus highlights the importance of vaccine boosters in this population.

A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein.

The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1-linker1-HR2-linker2-HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.

Who is next: rising star prediction via diffusion of user interest in social networks (preprint)

Finding items with potential to increase sales is of great importance in online market. In this paper, we propose to study this novel and practical problem: rising star prediction. We call these potential items Rising Star, which implies their ability to rise from low-turnover items to best-sellers in the future. Rising stars can be used to help with unfair recommendation in e-commerce platform, balance supply and demand to benefit the retailers and allocate marketing resources rationally. Although the study of rising star can bring great benefits, it also poses challenges to us. The sales trend of rising star fluctuates sharply in the short-term and exhibits more contingency caused by some external events (e.g., COVID-19 caused increasing purchase of the face mask) than other items, which cannot be solved by existing sales prediction methods. To address above challenges, in this paper, we observe that the presence of rising stars is closely correlated with the early diffusion of user interest in social networks, which is validated in the case of Taocode (an intermediary that diffuses user interest in Taobao). Thus, we propose a novel framework, RiseNet, to incorporate the user interest diffusion process with the item dynamic features to effectively predict rising stars. Specifically, we adopt a coupled mechanism to capture the dynamic interplay between items and user interest, and a special designed GNN based framework to quantify user interest. Our experimental results on large-scale real-world datasets provided by Taobao demonstrate the effectiveness of our proposed framework.

Combining Direct PCR Technology and Capillary Electrophoresis for an Easy-to-Operate and Highly Sensitive Infectious Disease Detection System for Shrimp.

Infectious diseases are considered the greatest threat to the modern high-density shrimp aquaculture industry. Specificity, rapidity, and sensitivity of molecular diagnostic methods for the detection of asymptomatic infected shrimp allows preventive measures to be taken before disease outbreaks. Routine molecular detection of pathogens in infected shrimp can be made easier with the use of a direct polymerase chain reaction (PCR). In this study, four direct PCR reagent brands were tested, and results showed that the detection signal of direct PCR in hepatopancreatic tissue was more severely affected. In addition, portable capillary electrophoresis was applied to improve sensitivity and specificity, resulting in a pathogen detection limit of 25 copies/PCR-reaction. Juvenile shrimp from five different aquaculture ponds were tested for white spot syndrome virus infection, and the results were consistent with the Organization for Animal Health's certified standard method. Furthermore, this methodology could be used to examine single post larvae shrimp. The overall detection time was reduced by more than 58.2%. Therefore, the combination of direct PCR and capillary electrophoresis for on-site examination is valuable and has potential as a suitable tool for diagnostic, epidemiological, and pathological studies of shrimp aquaculture.