RLR-mediated type I IFN production plays a pivotal role in elevating host immunity for viral clearance and cancer immune surveillance. Here, we report that glycolysis, which is inactivated during RLR activation, serves as a barrier to impede type I IFN production upon RLR activation. RLR-triggered MAVS-RIG-I recognition hijacks hexokinase binding to MAVS, leading to the impairment of hexokinase mitochondria localization and activation. Lactate serves as a key metabolite responsible for glycolysis-mediated RLR signaling inhibition by directly binding to MAVS transmembrane (TM) domain and preventing MAVS aggregation. Notably, lactate restoration reverses increased IFN production caused by lactate deficiency. Using pharmacological and genetic approaches, we show that lactate reduction by lactate dehydrogenase A (LDHA) inactivation heightens type I IFN production to protect mice from viral infection. Our study establishes a critical role of glycolysis-derived lactate in limiting RLR signaling and identifies MAVS as a direct sensor of lactate, which functions to connect energy metabolism and innate immunity.

Highlights d Comprehensive diagrams for comparing the features of the three systems d An open source versatile pipeline for all systems d Systematic comparison on sensitivity, precision, bias, and costs d Demonstration of Smart-seq2 protocols with inDrop platform

Background COVID-19 vaccines will become available in China soon. Understanding communities’ responses to the forthcoming COVID-19 vaccines is important. We applied the theory of planned behavior as the theoretical framework. Objective This study investigates the prevalence of and factors associated with behavioral intention to receive self-financed or free COVID-19 vaccinations among Chinese factory workers who resumed work during the pandemic. We examined the effects of factors including sociodemographics, perceptions related to COVID-19 vaccination, exposure to information about COVID-19 vaccination through social media, and COVID-19 preventive measures implemented by individuals and factories. Methods Participants were full-time employees 18 years or older who worked in factories in Shenzhen. Factory workers in Shenzhen are required to receive a physical examination annually. Eligible workers attending six physical examination sites were invited to complete a survey on September 1-7, 2020. Out of 2653 eligible factory workers, 2053 (77.4%) completed the online survey. Multivariate two-level logistic regression models and ordinal logistic regression models were fitted. Results The prevalence of behavioral intention to receive a COVID-19 vaccination was 66.6% (n=1368, conditional on 80% vaccine efficacy and market rate) and 80.6% (n=1655, conditional on 80% vaccine efficacy and free vaccines). After adjusting for significant background characteristics, positive attitudes toward COVID-19 vaccination (adjusted odds ratio [AOR] 1.20, 95% CI 1.15-1.25 and AOR 1.24, 95% CI 1.19-1.30), perceived support from significant others for getting a COVID-19 vaccination (AOR 1.43, 95% CI 1.32-1.55 and AOR 1.37, 95% CI 1.25-1.50), and perceived behavioral control to get a COVID-19 vaccination (AOR 1.51, 95% CI 1.32-1.73 and AOR 1.28, 95% CI 1.09-1.51) were positively associated with both dependent variables (conditional on 80% vaccine efficacy and market rate or free vaccines, respectively). Regarding social media influence, higher frequency of exposure to positive information related to COVID-19 vaccination was associated with a higher intention to receive a COVID-19 vaccination at market rate (AOR 1.53, 95% CI 1.39-1.70) or a free vaccination (AOR 1.52, 95% CI 1.35-1.71). Higher self-reported compliance with wearing a face mask in the workplace (AOR 1.27, 95% CI 1.02-1.58 and AOR 1.67, 95% CI 1.24-2.27) and other public spaces (AOR 1.80, 95% CI 1.42-2.29 and AOR 1.34, 95% CI 1.01-1.77), hand hygiene (AOR 1.21, 95% CI 1.00-1.47 and AOR 1.52, 95% CI 1.19-1.93), and avoiding social gatherings (AOR 1.22, 95% CI 1.01-1.47 and AOR 1.55, 95% CI 1.23-1.95) and crowded places (AOR 1.24, 95% CI 1.02-1.51 and AOR 1.73, 95% CI 1.37-2.18) were also positively associated with both dependent variables. The number of COVID-19 preventive measures implemented by the factory was positively associated with the intention to receive a COVID-19 vaccination under both scenarios (AOR 1.08, 95% CI 1.04-1.12 and AOR 1.06, 95% CI 1.01-1.11). Conclusions Factory workers in China reported a high behavioral intention to receive a COVID-19 vaccination. The theory of planned behavior is a useful framework to guide the development of future campaigns promoting COVID-19 vaccination.

SummarySince its debut in 2009, single-cell RNA-seq has been a major propeller behind biomedical research progress. Developmental biology and stem cell studies especially benefit from the ability to profile single cells. While most studies still focus on individual tissues or organs, recent development of ultra-high-throughput single-cell RNA-seq has demonstrated potential power to depict more complexed system or even the entire body. Though multiple ultra-high-throughput single-cell RNA-seq systems have acquired attention, systematic comparison of these systems is yet available. Here we focus on three prevalent droplet-based ultrahigh-throughput single-cell RNA-seq systems, inDrop, Drop-seq, and 10X Genomics Chromium. While each system is capable of profiling single-cell transcriptome, detailed comparison revealed distinguishing features and suitable application scenario for each system.