Chinese Guideline on Allergen Immunotherapy for Allergic Rhinitis: The 2022 Update.

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.

How rumors diffuse in the infodemic: Evidence from the healthy online social change in China

Infodemic is defined as ‘an overabundance of information-some accurate and some not-that makes it hard for people to find trustworthy sources and reliable guidance when they need it’ by the World Health Organization. As unverified information, rumors can widely spread in online society, further diffusing infodemic. Existed studies mainly focused on rumor detection and prediction from the statement itself and give the probability that it will evolve into a rumor in the future. However, the detection and prediction from rumors production perspective is lack. This research explores the production mechanism from the uncertainty perspective using the data from Weibo and public rumor data set. Specifically, we identify the public uncertainty through user-generated content on social media based on systemic functional linguistics theory. Then we empirically verify the promoting effect of uncertainty on rumor production and constructed a model for rumor prediction. The fitting effect of the empirical model with the public uncertainty is significantly better than that with only control variables, indicating that our framework identifies public uncertainty well and uncertainty has a significantly predictive effect on rumors. Our study contributes to the research of rumor prediction and uncertainty identification, providing implications for healthy online social change in the post-epidemic era.

Why SARS-CoV-2 Omicron variant is milder? A single high-frequency mutation of structural envelope protein matters. (preprint)

SARS-CoV-2 Omicron variant is highly transmissible and extensive morbidity, which has raised concerns for antiviral therapy. In addition, the molecular basis for the attenuated pathogenicity and replication capacity of Omicron remains elusive. Here, we report for the first time that a high-frequency mutation T9I on 2-E of SARS-CoV-2 variant Omicron forms a non-selective ion channel with abolished calcium permeability and reduced acid sensitivity compared to the WT channel. In addition, T9I caused less cell death and a weaker cytokine production. The channel property changes might be responsible for the Omicron variant releases less efficiently and induces a comparatively lower level of cell damage in the infected cells. Our study gives valuable insights into key features of the Omicron variant, further supporting 2-E is a promising drug target against SARS-CoV-2 and providing critical information for the COVID-19 treatment.

Structures of the Omicron spike trimer with ACE2 and an anti-Omicron antibody: mechanisms for the high infectivity, immune evasion and antibody drug discovery (preprint)

The Omicron variant of SARS-CoV-2 has rapidly become the dominant infective strain and the focus efforts against the ongoing COVID-19 pandemic. Here we report an extensive set of structures of the Omicron spike trimer by its own or in complex with ACE2 and an anti-Omicron antibody. These structures reveal that most Omicron mutations are located on the surface of the spike protein, which confer stronger ACE2 binding by nearly 10 folds but become inactive epitopes resistant to many therapeutic antibodies. Importantly, both RBD and the closed conformation of the Omicron spike trimer are thermodynamically unstable, with the melting temperature of the Omicron RBD decreased by as much as 7°C, making the spiker trimer prone to random open conformations. An unusual RBD-RBD interaction in the ACE2-spike complex unique to Omicron is observed to support the open conformation and ACE2 binding, serving the basis for the higher infectivity of Omicron. A broad-spectrum therapeutic antibody JMB2002, which has completed Phase 1 clinical trial, is found to interact with the same two RBDs to inhibit ACE2 binding, in a mode that is distinguished from all previous antibodies, thus providing the structural basis for the potent inhibition of Omicron by this antibody. Together with biochemical data, our structures provide crucial insights into higher infectivity, antibody evasion and inhibition of Omicron.

A silver lining in the COVID-19 cloud: examining customers’ value perceptions, willingness to use and pay more for robotic restaurants

The COVID-19 pandemic has severely affected the restaurant industry due to enforced closures and limitations on social gatherings, prompting restaurateurs to innovate and adapt in order to ensure the viability of their businesses. Pandemic has also induced changes in our perceptions of safety in public spaces, necessitating the adoption of social distancing and more widespread use of online platforms for purchasing and communication. While the pandemic might be a catalyst for the adoption of contactless technologies, some restaurateurs remain hesitant to invest in service robots because they are not convinced of the return on investment and the potential value service robots can deliver to their customers. Therefore, this study aims to explore customer value perceptions of service robots and their impact on customers’ attitudes and behaviors toward robotic restaurants. Findings yielded by a survey of 445 potential diners in Taiwan show that customers’ willingness to use and to pay more for robotic restaurants are determined by their attitudes toward robots, which are influenced by functional, conditional, epistemic, emotional, co-creation, and social values. Our survey results also reveal that the importance of conditional value is amplified by crisis-specific antecedents, namely the need for physical distancing and mysophobia. These findings have implications for restaurant pricing policies and can be considered by restaurant managers when formulating strategies aimed at sustaining their business in these challenging times. (English) [ABSTRACT FROM AUTHOR] 由于强制关闭和限制社交聚会，COVID-19大流行严重影响了餐饮业，促使餐馆经营者进行创新和调整，以确保其业务的生存能力. 流感大流行还导致我们对公共场所安全的看法发生了变化，这就需要采用社交距离，并更广泛地使用在线购物和交流平台. 虽然这种流行病可能是采用非接触式技术的催化剂，但一些餐馆老板仍然对投资服务机器人犹豫不决，因为他们不相信服务机器人能给顾客带来的投资回报和潜在价值. 因此，本研究旨在探讨顾客对服务机器人的价值认知及其对顾客对机器人餐厅态度与行为的影响. 对台湾445位潜在食客的调查结果显示，顾客对机器人餐厅的态度决定了他们对机器人餐厅的使用意愿和支付意愿，这些态度受到功能、条件、认知、情感、共同创造和社会价值观的影响. 我们的调查结果还显示，条件价值的重要性被特定危机的前因放大，即需要身体距离和神秘恐惧症. 这些发现对餐厅定价政策有一定的启示，可供餐厅经理在制定策略时加以考虑，以期在这个充满挑战的时代维持其业务. (Chinese) [ABSTRACT FROM AUTHOR] Copyright of Journal of Hospitality Marketing & Management is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Longitudinal transcriptome analyses show robust T cell immunity during recovery from COVID-19.

Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for improving treatment. Here, we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell (PBMC) samples from 18 patients with coronavirus disease 2019 (COVID-19) during their treatment, convalescence, and rehabilitation. After analyzing the regulatory networks of differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) between the different clinical stages, we found that humoral immunity and type I interferon response were significantly downregulated, while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19. The formation of this T cell immune response might be driven by the activation of activating protein-1 (AP-1) related signaling pathway and was weakly affected by other clinical features. These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damage and constitutes an antiviral target (preprint)

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of the virus excessively damaging abilities remains unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is sufficient to cause acute respiratory distress syndrome (ARDS)-like damage in vitro and in vivo. Overexpression of 2-E protein induced rapid pyroptosis-like cell death in various susceptible cells and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damage in lung and spleen. Overexpressed 2-E protein formed cation channels in host cell membranes, eventually leading to membrane rupture. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent protective effects against the 2-E-induced damage both in vitro and in vivo. Importantly, their channel inhibition, cell protection and antiviral activities were positively correlated with each other, supporting 2-E is a promising drug target against SARS-CoV-2.

Structure-Based Design, Synthesis and Biological Evaluation of Peptidomimetic Aldehydes as a Novel Series of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease (preprint)

SARS-CoV-2 is the etiological agent responsible for the COVID-19 outbreak in Wuhan. Specific antiviral drug are urgently needed to treat COVID-19 infections. The main protease (Mpro) of SARS-CoV-2 is a key CoV enzyme that plays a pivotal role in mediating viral replication and transcription, which makes it an attractive drug target. In an effort to rapidly discover lead compounds targeting Mpro, two compounds (11a and 11b) were designed and synthesized, both of which exhibited excellent inhibitory activity with an IC50 value of 0.05 M and 0.04 M respectively. Significantly, both compounds exhibited potent anti-SARS-CoV-2 infection activity in a cell-based assay with an EC50 value of 0.42 M and 0.33 M, respectively. The X-ray crystal structures of SARS-CoV-2 Mpro in complex with 11a and 11b were determined at 1.5 [A] resolution, respectively. The crystal structures showed that 11a and 11b are covalent inhibitors, the aldehyde groups of which are bound covalently to Cys145 of Mpro. Both compounds showed good PK properties in vivo, and 11a also exhibited low toxicity which is promising drug leads with clinical potential that merits further studies.