Deep Learning-based Network Pharmacology for Exploring the Mechanism of Licorice for the Treatment of COVID-19 (preprint)

Licorice, a traditional Chinese medicine, has been widely used for the treatment of COVID-19, but all active compounds and the corresponding targets are still not clear. Therefore, this study proposed a deep learning-based network pharmacology approach to identify more potential active compounds and targets of licorice and to collect information regarding different representative compounds. A graph convolutional neural network was used to construct a molecular map and a convolutional neural network was used to develop a Morgan fingerprint. Twenty core compounds and 6 core targets were predicted, among which 4 compounds (quercetin, naringenin, liquiritigenin, and licoisoflavanone), 2 targets (SYK and JAK2) and the relevant pathways (P53, cAMP, and NF-kB) were associated with SARS-CoV-2-infection, which were confirmed by previous studies. In addition, 2 new active compounds (glabrone and vestitol) and 2 new targets (PTEN and MAP3K8) were further validated by molecular docking, and the results showed that these active compounds bound to SARS-CoV-2 related targets, including the main protease (Mpro, also called 3CLpro), the spike protein (S protein), and the angiotensin-converting enzyme 2 (ACE2). Overall, we conclude that the findings of this study has the value of further exploration in the following experiment and clinical application.

Ground-level ozone pollution in China: a synthesis of recent findings on influencing factors and impacts

Ozone (O3) in the troposphere is an air pollutant and a greenhouse gas. In mainland China, after the Air Pollution Prevention and Action Plan was implemented in 2013—and despite substantial decreases in the concentrations of other air pollutants—ambient O3 concentrations paradoxically increased in many urban areas. The worsening urban O3 pollution has fuelled numerous studies in recent years, which have enriched knowledge about O3-related processes and their impacts. In this article, we synthesise the key findings of over 500 articles on O3 over mainland China that were published in the past six years in English-language journals. We focus on recent changes in O3 concentrations, their meteorological and chemical drivers, complex O3 responses to the drastic decrease in human activities during coronavirus disease 2019 lockdowns, several emerging chemical processes, impacts on crops and trees, and the latest government interventions.

Analysis on Action Tracking Reports of COVID-19 Informs Control Strategies and Vaccine Delivery in Post-Pandemic Era (preprint)

Understanding the spread of SARS-CoV-2 provides important insights for control policies such as social-distancing interventions and vaccine delivery in the post-pandemic era. In this work, we take the advantage of action tracking reports of confirmed COVID-19 patients, which contain details regarding the mobility trajectory of a patient, along with the people with whom the patient has interacted, the timing of diagnosis, and personal information (e.g., age and sex). We analyzed reports of 4,410 patients from April 2020 to February 2021 in China, a country where the residents are well-prepared for the "new normal" world following COVID-19 spread. We developed natural language processing (NLP) tools to transform the unstructured text of action-tracking reports to a structured network of social contacts. A SEIR model was built on top of the network, and was able to capture important aspects regarding coronavirus transmissions such as location category, age, sex and socioeconomic status. Our analysis provides important insights for the development of control policies. Under the "new normal" conditions, we find that restaurants, locations less protected by mask-wearing, have a greater risk than any other location categories, including locations where people are present at higher densities (e.g., flight). We find that discouraging railway transports is crucial to avoid another wave of breakout during the Chunyun season (a period of travel in China with extremely high traffic load around the Chinese New Year). By formalizing the challenge of finding the optimal vaccine delivery among various different population groups (e.g., sex, age and socioeconomic groups) as an optimization problem, our analysis helps to maximize the efficiency of vaccine delivery under the general situation of vaccine supply shortage. We are able to reduce the numbers of infections and deaths by 7.4% and 10.5% respectively with vaccine supply for only 1% of the population. Furthermore, with 10% vaccination rate, the numbers of infections and deaths further decrease by 52.6% and 78.1% respectively. Our work will be helpful in the design of effective policies regarding interventions, reopening, contact tracing and vaccine delivery in the "new normal" world following COVID-19 spread.

Associations of COVID-19 Pandemic with Clinical Manifestations Among the Uninfected Pregnant Women in China: A Combined Cohort Study (preprint)

Background: Whether coronavirus disease 2019 (COVID-19) pandemic would affect pregnancy-associated factors of uninfected pregnant women was rarely reported.Methods: A total of 32,277 pregnant women from six sites (Hubei Province, Guangdong Province, Hebei Province, Shandong Province, Yunnan Province and Beijing City) were finally recruited. We conducted a retrospective combined cohort study to analyze the associations between the number of prenatal examinations (NPE), delivery gestational week (DGW), the risk of caesarean section (CS), stillbirth, neonatal weight, preterm birth, macrosomia, small for gestational age (SGA), large for gestational age (LGA) and the COVID-19 in two time-periods, the pre-pandemic period (P-2019, 1/1/19-5/31/19) and the pandemic period (P-2020, 1/1/20-5/31/20).Findings: After adjusting for other covariates, we found the NPE, DGW, and SGA were negatively associated with the COVID-19 pandemic, whereas the CS and preterm birth rates were positively associated with the COVID-19, with adjusted relative risks (aRRs) of 1.11 [95% confidence interval (CI) 1.06–1.17] and 1.37 (95% CI: 1.02–1.84) respectively in Hubei. For Guangdong, the associations of CS and preterm birth with the COVID-19 were similar in Hubei. In contrast, limited associations were evident in other areas, except for a positive association with macrosomia [aRR = 1.26 (95% CI: 1.03–1.55)] in Beijing.Interpretation: The CS and preterm birth rates increased slightly in areas that were more affected by the pandemic than other areas among uninfected pregnant women. NPEs were not significantly interrupted and most maternal and neonatal clinical characteristics were within the normal ranges.Funding: National Key Research and Development Program, National Natural Science Foundation of China and National Health Commission Capacity Building and Continuing Education Center.Declaration of Interests: All authors declare to have no conflict of interest.Ethics Approval Statement: The study was approved by the Peking University ethics board (no. IRB00001052-20025).

SARS pandemic exposure impaired early childhood development: A lesson for COVID-19 (preprint)

Social and mental stressors associated with the COVID-19 pandemic may promote long-term effects on child development. However, reports aimed at identifying the relationship between pandemics and child health are limited. We conducted a retrospective study to evaluate the severe acute respiratory syndrome (SARS) pandemic in 2003 and its relationship to child development indicators using a representative sample across China. Our study involved longitudinal measurements of 14,647 children, 36% of whom (n = 5216) were born before or during the SARS pandemic. Cox models were utilized to examine the effects of SARS on preterm birth and four milestones of development: age to (1) walk independently, (2) say a complete sentence, (3) count from 0 to 10, and (4) undress him/herself for urination. Mixed effect models were utilized to associate SARS with birthweight, body weight and height. Our results show that experiencing SARS during early childhood was significantly associated with delayed milestones, with adjusted hazard ratios of 3.17 [95% confidence intervals (CI): 2.71, 3.70], 3.98 (3.50, 4.53), 4.96 (4.48, 5.49), or 5.57 (5.00, 6.20) for walking independently, saying a complete sentence, counting from 0 to 10, and undressing him/herself for urination, respectively. Experiencing SARS was also associated with reduced body weight. This effect was strongest for preschool children [a weight reduction of 4.86 (0.36, 9.35) kg, 5.48 (-0.56, 11.53) kg or 5.09 (-2.12, 12.30) kg for 2, 3, 4 year-olds, respectively]. We did not identify a significant effect of maternal SARS exposure on birthweight or gestational length. Collectively, our results showed that the SARS pandemic was associated with delayed child development and provided epidemiological evidence to support the association between infectious disease epidemics and impaired child health. These results provide a useful framework to investigate and mitigate relevant impacts from the COVID-19 pandemic.