A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen Years.

Structure-based virtual screening (SBVS), also known as molecular docking, has been increasingly applied to discover small-molecule ligands based on the protein structures in the early stage of drug discovery. In this review, we comprehensively surveyed the prospective applications of molecular docking judged by solid experimental validations in the literature over the past fifteen years. Herein, we systematically analyzed the novelty of the targets and the docking hits, practical protocols of docking screening, and the following experimental validations. Among the 419 case studies we reviewed, most virtual screenings were carried out on widely studied targets, and only 22% were on less-explored new targets. Regarding docking software, GLIDE is the most popular one used in molecular docking, while the DOCK 3 series showed a strong capacity for large-scale virtual screening. Besides, the majority of identified hits are promising in structural novelty and one-quarter of the hits showed better potency than 1 µM, indicating that the primary advantage of SBVS is to discover new chemotypes rather than highly potent compounds. Furthermore, in most studies, only in vitro bioassays were carried out to validate the docking hits, which might limit the further characterization and development of the identified active compounds. Finally, several successful stories of SBVS with extensive experimental validations have been highlighted, which provide unique insights into future SBVS drug discovery campaigns.

The irreplaceable role of medical massive open online courses in China during the COVID-19 pandemic.

BACKGROUND: Massive open online courses (MOOCs) have become innovative open-learning approach in medical education. This study aimed to evaluate the dynamic changes in the construction and application of medical MOOCs before and after the coronavirus disease 2019 (COVID-19) pandemic in China. METHODS: The dynamic changes of usages about medical MOOCs before and after 2020 were mainly searched on the Smart Education of China Higher Education platform, and the detailed learning profiles and outcome indicators were further analyzed using 40 national first-class medical MOOCs from 'zhihuishu' platform. RESULTS: A total of 2,405 medical MOOCs were exported from the Smart Education of China Higher Education platform, of which 1,313 (54.6%) were launched since 2020. The total and average numbers of participants of 141 national first-class medical MOOCs peaked during the initial spread of COVID-19 in 2020. We further analyzed the dynamic usage of MOOCs from 2018 to 2022 based on 40 national first-class medical MOOCs launched on the 'Zhihuishu' platform. The findings revealed that the number of registered learners (3,240 versus 2,654), questions and answers (27,005 versus 5,116) and students taking the final examination (2,782 versus 1,995) per semester were significantly higher since 2020 compared to these before 2020. Especially, the number of registered learners, registered schools, questions and answers, and students participating in online discussion, taking the unit quiz, taking final examinations and passing final examinations all peaked in the 2020 spring-summer semester. Pearson's correlation analysis found that the number of questions and answers and the number of learners who participated in online discussion were both positively correlated with the number of students who passed the final examination, and the correlation was especially strong since 2020. Moreover, the number of publications on medical MOOC research has soared since 2020 and has maintained a continuous upward trend. CONCLUSIONS: High-quality medical MOOCs have been launched rapidly since the COVID-19 pandemic in China. The number of participants and online interactions of medical MOOCs peaked during the initial spread of COVID-19 in 2020. MOOCs are reliable and valid digital sources that facilitate medical higher education and play irreplaceable roles in emergency management.

Large-scale, national, family-based epidemiological study on Helicobacter pylori infection in China: the time to change practice for related disease prevention.

BACKGROUND AND AIMS: Current practice on Helicobacter pylori infection mostly focuses on individual-based care in the community, but family-based H. pylori management has recently been suggested as a better strategy for infection control. However, the family-based H. pylori infection status, risk factors and transmission pattern remain to be elucidated. METHODS: From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based H. pylori infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for H. pylori infection. RESULTS: Among all participants, the average individual-based H. pylori infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1-7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p<0.05). CONCLUSION: Familial H. pylori infection rate is high in general household in China. Exposure to infected family members is likely the major source of its spread. These results provide supporting evidence for the strategic changes from H. pylori individual-based treatment to family-based management, and the notion has important clinical and public health implications for infection control and related disease prevention.

Combined lifestyle, mental health, and mortality in US cancer survivors: a national cohort study.

BACKGROUND: Adopting healthy lifestyles and staying mentally health are two cost-effective modifiable strategies that cancer survivors can implement in self-management. We aimed to evaluate the independent, mediation, interaction, and joint associations of combined lifestyle and mental health with mortality in cancer survivors. METHODS: We performed a cohort study including 3145 cancer survivors from National Health and Nutrition Examination Survey (2005-2018). A healthy lifestyle score was constructed based on post-diagnosis body mass index, physical activity, diet, smoking, and drinking. Post-diagnosis mental health was assessed by Patient Health Questionnaire (PHQ-9). Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cancer, and non-cancer mortality were computed using Cox proportional hazards regression models. RESULTS: After 20,900 person-years of follow-up (median, 6.3 years), cancer survivors with higher lifestyle score had decreased mortality, independent of mental health. Compared to participants with lower lifestyle score (0-1), HRs (95% CIs) for all-cause and non-cancer mortality among those with higher lifestyle score (3-5) were 0.68 (0.52-0.89) and 0.69 (0.56-0.85), respectively. 6.2-10.3% of the associations were mediated by mental health. Similar trends were observed among participants categorized by mental health, those with better mental health had lower mortality, independent of lifestyle. Participants with better mental health benefited more from adopting healthy lifestyles, and vice versa. Combinations of higher healthy lifestyle score and better mental health were associated with significant decreased mortality, the lowest mortality was seen in participants with highest healthy lifestyle score and concurrently with best mental health. CONCLUSIONS: For the first time, in this cohort study with a nationally representative sample of US cancer survivors, we comprehensively explored the complex associations of lifestyle, mental health, and mortality. Evidence derived from this study may give much confidence to cancer survivors and healthcare providers that, changing one's lifestyle and/or staying mentally healthy after cancer diagnosis can improve survival.

Distinct gut microbiota and health outcomes in asymptomatic infection, viral nucleic acid test re-positive, and convalescent COVID-19 cases

Gut microbiota composition is suggested to associate with coronavirus disease 2019 (COVID-19) severity, but the impact of gut microbiota on health outcomes is largely unclear. We recruited 81 individuals from Wuhan, China, including 13 asymptomatic infection cases (Group A), 24 COVID-19 convalescents with adverse outcomes (Group C), 31 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) re-positive cases (Group D), and 13 non-COVID-19 healthy controls (Group H). The microbial features of Groups A and D were similar and exhibited higher gut microbial diversity and more abundant short-chain fatty acid (SCFA)-producing species than Group C. Group C was enriched with opportunistic pathogens and virulence factors related to adhesion and toxin production. The abundance of SCFA-producing species was negatively correlated, while Escherichia coli was positively correlated with adverse outcomes. All three groups (A, C, and D) were enriched with the mucus-degrading species Akkermansia muciniphila, but decreased with Bacteroides-encoded carbohydrate-active enzymes. The pathways of vitamin B6 metabolic and folate biosynthesis were decreased, while selenocompound metabolism was increased in the three groups. Specifically, the secondary bile acid (BA) metabolic pathway was enriched in Group A. Antibiotic resistance genes were common among the three groups. Conclusively, the gut microbiota was related to the health outcomes of COVID-19. Dietary supplementations (SCFAs, BA, selenium, folate, vitamin B6) may be beneficial to COVID-19 patients.

Potential of Endogenous Oxytocin in Endocrine Treatment and Prevention of COVID-19.

Coronavirus disease 2019 or COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a significant threat to the health of human beings. While wearing mask, maintaining social distance and performing self-quarantine can reduce virus spreading passively, vaccination actively enhances immune defense against COVID-19. However, mutations of SARS-CoV-2 and presence of asymptomatic carriers frustrate the effort of completely conquering COVID-19. A strategy that can reduce the susceptibility and thus prevent COVID-19 while blocking viral invasion and pathogenesis independent of viral antigen stability is highly desirable. In the pathogenesis of COVID-19, endocrine disorders have been implicated. Correspondingly, many hormones have been identified to possess therapeutic potential of treating COVID-19, such as estrogen, melatonin, corticosteroids, thyroid hormone and oxytocin. Among them, oxytocin has the potential of both treatment and prevention of COVID-19. This is based on oxytocin promotion of immune-metabolic homeostasis, suppression of inflammation and pre-existing comorbidities, acceleration of damage repair, and reduction of individuals' susceptibility to pathogen infection. Oxytocin may specifically inactivate SARS-COV-2 spike protein and block viral entry into cells via angiotensin-converting enzyme 2 by suppressing serine protease and increasing interferon levels and number of T-lymphocytes. In addition, oxytocin can promote parasympathetic outflow and the secretion of body fluids that could dilute and even inactivate SARS-CoV-2 on the surface of cornea, oral cavity and gastrointestinal tract. What we need to do now is clinical trials. Such trials should fully balance the advantages and disadvantages of oxytocin application, consider the time- and dose-dependency of oxytocin effects, optimize the dosage form and administration approach, combine oxytocin with inhibitors of SARS-CoV-2 replication, apply specific passive immunization, and timely utilize efficient vaccines. Meanwhile, blocking COVID-19 transmission chain and developing other efficient anti-SARS-CoV-2 drugs are also important. In addition, relative to the complex issues with drug applications over a long term, oxytocin can be mobilized through many physiological stimuli, and thus used as a general prevention measure. In this review, we explore the potential of oxytocin for treatment and prevention of COVID-19 and perhaps other similar pathogens.

Recent advances and perspectives of postoperative neurological disorders in the elderly surgical patients.

Postoperative neurological disorders, including postoperative delirium (POD), postoperative cognitive dysfunction (POCD), postoperative covert ischemic stroke, and hemorrhagic stroke, are challenging clinical problems in the emerging aged surgical population. These disorders can deteriorate functional outcomes and long-term quality of life after surgery, resulting in a substantial social and financial burden to the family and society. Understanding predisposing and precipitating factors may promote individualized preventive treatment for each disorder, as several risk factors are modifiable. Besides prevention, timely identification and treatment of etiologies and symptoms can contribute to better recovery from postoperative neurological disorders and lower risk of long-term cognitive impairment, disability, and even death. Herein, we summarize the diagnosis, risk factors, prevention, and treatment of these postoperative complications, with emphasis on recent advances and perspectives.

Clinical and Virological Features of the First Occurrence of COVID-19 Delta Variant in Anhui Province, China (preprint)

Objectives Since the outbreak of coronavirus disease 2019 (COVID-19), it has caused serious casualties worldwide. In recent months, the virus has mutated into an increasingly infectious form (Delta variant) and spread rapidly.Methods In the current study, we analyzed the clinical, epidemiological and viral genetic characteristics of the first four imported Delta cases in Anhui Province, China.Results The four imported Delta cases developed chest inflammation, tissue damage and recovered after admission, the serum high-sensitivity C-reactive protein (hs-CRP) and CRP levels showed a first increasing and then decreasing trend. The changes of hs-CRP /CRP and serum neutralizing antibodies (Nab) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels were associated with the regression of chest lesions. The combination of genetic sequencing and epidemiological analysis suggested that the SARS-CoV-2 delta variant infection of these four patients may originate from Russia.Conclusions Our study found the certain correlations of serum hs-CRP/CRP and Nab levels with the occurrence, development and outcome of COVID-19 delta variant, suggesting that monitoring hs-CRP/CRP and Nab levels of COVID-19 delta variant patients at hospital admission may be useful for understanding the severity of patients’ current conditions.

AIoT Used for COVID-19 Pandemic Prevention and Control.

The pandemic of COVID-19 is continuing to wreak havoc in 2021, with at least 170 million victims around the world. Healthcare systems are overwhelmed by the large-scale virus infection. Luckily, Internet of Things (IoT) is one of the most effective paradigms in the intelligent world, in which the technology of artificial intelligence (AI), like cloud computing and big data analysis, is playing a vital role in preventing the spread of the pandemic of COVID-19. AI and 5G technologies are advancing by leaps and bounds, further strengthening the intelligence and connectivity of IoT applications, and conventional IoT has been gradually upgraded to be more powerful AI + IoT (AIoT). For example, in terms of remote screening and diagnosis of COVID-19 patients, AI technology based on machine learning and deep learning has recently upgraded medical equipment significantly and has reshaped the workflow with minimal contact with patients, so medical specialists can make clinical decisions more efficiently, providing the best protection not only to patients but also to specialists themselves. This paper reviews the latest progress made in combating COVID-19 with both IoT and AI and also provides comprehensive details on how to combat the pandemic of COVID-19 as well as the technologies that may be applied in the future.

Risk factors for myocardial injury at admission of 325 patients with coronavirus disease 2019 in Shanghai, China.

OBJECTIVE: Myocardial injury leads to higher mortality in COVID-19, but the causes and risk factors are variable. We evaluated the potential risk factors for myocardial injury in COVID-19 patients to improve treatment strategies and reduce mortality. METHODS: This retrospective analysis enrolled 325 COVID-19 patients in Shanghai, China. RESULTS: The median age in our cohort was 51 [range 15-88] years, 26 (8%) were critically ill, and 177 patients (19.7%) had myocardial injury. The myocardial injury group comprised older, more critically ill patients with hypertension, other comorbidities, history of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, lower peripheral blood lymphocyte count and higher D-dimer levels. Binary logistic regression analysis identified only age was an independent risk factor for myocardial injury (odds ratio 1.019; 95% confidence interval 1.003-1.036; age increase by 1 year = myocardial injury risk increase by 1.9%). CONCLUSIONS: Older age was associated with a higher incidence of myocardial injury for COVID-19 patients.

Predictive Value of Eosinophil Count on COVID-19 Disease Progression and Outcomes, a Retrospective Study of Leishenshan Hospital in Wuhan, China.

BACKGROUND: The potential protective role of eosinophils in the COVID-19 pandemic has aroused great interest, given their potential virus clearance function and the infection resistance of asthma patients to this coronavirus. However, it is unknown whether eosinophil counts could serve as a predictor of the severity of COVID-19. METHODS: A total of 1004 patients with confirmed COVID-19 who were admitted to Leishenshan Hospital in Wuhan, China, were enrolled in this study, including 905 patients in the general ward and 99 patients in the intensive care unit (ICU). We reviewed their medical data to analyze the association between eosinophils and ICU admission and death. RESULTS: Of our 1004 patients with COVID-19, low eosinophil counts/ratios were observed in severe cases. After adjusting for confounders that could have affected the outcome, we found that eosinophil counts might not be a predictor of ICU admission. In 99 ICU patients, 58 of whom survived and 41 of whom died, low eosinophil level was an indicator of death in severe COVID-19 patients with a cutoff value of 0.04 × 109/L, which had an area under the curve of 0.665 (95% CI = 1.089-17.839; P = .045) with sensitivity and specificity of 0.569 and 0.7317, respectively. CONCLUSION: Our research revealed that a low eosinophil level is a predictor of death in ICU patients rather than a cause of ICU admission.

Prevalence of Self-Reported Symptoms of Computer Vision Syndrome and Associated Risk Factors among School Students in China during the COVID-19 Pandemic.

PURPOSE: To determine the prevalence and risk factors of self-reported symptoms of Computer Vision Syndrome (CVS) in school students during COVID-19 pandemic. METHODS: In this cross-sectional study in Nanjing, China, students (grades 1-12) from six randomly selected schools self-administered the online survey questionnaire about hours on electronic devices, outdoor activities, frequency and intensity of 17 CVS symptoms during virtual learning period of COVID-19 pandemic. RESULTS: Among 2363 invited students, 2005 (84.8%) completed the survey. Mean (SD) age was 12 (3.0) years, 51% were male, 53% wore glasses, 56% did not know the 20-20-20 rule (take a 20 second break every 20 min of close work and gaze at objects at least 20 feet away) and 6.5% knew but never followed the 20-20-20 rule. Mean (SD) hours/day was 4.6 (3.4) for screen time and 1.2 (1.0) for outdoor activities. Total of 1543 (77.0%) students reported at least one CVS symptom (median = 4) with eye dryness and itching the most common (48%). In multivariable analysis, CVS score 4 or more was independently associated with older age (adjusted odds ratio (aOR) = 1.05 for per-year increase, p = 0.02), children with myopia not wearing glasses (aOR = 2.12, p = 0.0003), astigmatism (aOR = 1.37, p = 0.04), other ocular diseases (aOR = 1.59, p = 0.005), not complying 20-20-20 rule (aOR = 2.13, p = 0.04), more screen time (aOR = 1.53 for >6 vs. ≤2 hours, p = 0.0001) and less outdoor activities (aOR = 1.37 for ≤0.6 vs. ≥1.9 hours, p = 0.005). CONCLUSIONS: During COVID-19 pandemic, self-reported CVS symptoms occurred in more than three-quarters of students. Besides pre-existing ocular diseases, children with myopia not wearing glasses, excessive time on screens, non-compliance of the 20-20-20 rule and reduced outdoor activities were associated with higher risk of CVS.

COVID-19-related stigma and its influencing factors: a nationwide cross-sectional study during the early stage of the pandemic in China.

OBJECTIVES: To describe the situation of COVID-19-related stigma towards patients with COVID-19 and people from the city of Wuhan in China and to assess the associations between COVID-19-related stigma, health literacy and sociodemographic characteristics during March 2020, the early stage of the pandemic. DESIGN: A cross-sectional online survey. SETTING: The study surveyed 31 provinces in China. PARTICIPANTS: This study surveyed 5039 respondents in China. OUTCOME MEASURES: Public stigma towards both patients with COVID-19 and Wuhan residents was measured. Binary logistic regression was used to identify the factors associated with public COVID-19-related stigma. RESULTS: Among the participants, 122 (2.4%) reported themselves and 254 (5.0%) reported the communities they lived in as holding a stigmatising attitude towards patients with COVID-19, respectively. Additionally, 114 (2.5%) and 475 (10.3%) reported that themselves and the communities they lived in, respectively, held a stigma against people from Wuhan, which was the most severely affected area in China. People aged over 40, lived in areas with severe epidemics (adjusted OR (aOR)=2.03, 95% CI (1.05 to 3.92)) and who felt it difficult to find and understand information about COVID-19 (aOR=1.91, 95% CI (1.08 to 3.37); aOR=1.88, 95% CI (1.08 to 3.29)) were more likely to stigmatise patients with COVID-19. People who were male, aged 41-50 and had difficulty understanding information (aOR=2.08, 95% CI (1.17 to 3.69)) were more likely to stigmatise people from Wuhan. CONCLUSIONS: Patients with COVID-19 and Wuhan residents suffered stigma at both the individual and the community levels. Those who had low health literacy, who lived in areas with a large number of COVID-19 cases and who were of ethnic minorities were more likely to stigmatise others. Tailored interventions are encouraged to improve health literacy and consequently to reduce public COVID-19-related stigma.

Risk factors for prolonged virus shedding of respiratory tract and fecal in adults with severe acute respiratory syndrome coronavirus-2 infection.

BACKGROUND: The dynamic alteration and comparative study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding pattern during treatment are limited. This study explores the potential risk factors influencing prolonged viral shedding in COVID-19. METHODS: A total of 126 COVID-19 patients were enrolled in this retrospective longitudinal study. A multivariate logistic regression analysis was carried out to estimate the potential risk factors. RESULTS: 38.1% (48/126) cases presented prolonged respiratory tract viral shedding, and 30 (23.8%) cases presented prolonged rectal swab viral shedding. Obesity (OR, 3.31; 95% CI, 1.08-10.09), positive rectal swab (OR, 3.43; 95% CI, 1.53-7.7), treatment by lopinavir/ritonavir with chloroquine phosphate (OR, 2.5; 95% CI, 1.04-6.03), the interval from onset to antiviral treatment more than 7 days (OR, 2.26; 95% CI, 1.04-4.93), lower CD4+ T cell (OR, 0.92; 95% CI, 0.86-0.99) and higher NK cells (OR, 1.11; 95% CI, 1.02-1.20) were significantly associated with prolonged respiratory tract viral shedding. CD3-CD56+ NK cells (OR, 0.87; 95% CI, 0.76-0.99) were related with prolonged fecal shedding. CONCLUSIONS: Obesity, delayed antiviral treatment, and positive SARS-CoV-2 for stool were independent risk factors for prolonged SARS-CoV-2 RNA shedding of the respiratory tract. A combination of LPV/r and abidol as the initial antiviral regimen was effective in shortening the duration of viral shedding compared with LPV/r combined with chloroquine phosphate. CD4+ T cell and NK cells were significantly associated with prolonged viral shedding, and further studies are to be warranted to determine the mechanism of immunomodulatory response in virus clearance.

COVID-19 vaccination intention and influencing factors among different occupational risk groups: a cross-sectional study.

As an effective measure to manage the Coronavirus disease 2019 (COVID-19) pandemic, the acceptance of the COVID-19 vaccine and understanding the influencing factors of vaccination intention is particularly important. This study aimed to describe the COVID-19 vaccination intention among three different occupational risk groups and identify influencing factors of vaccination intention since a COVID-19 vaccine is available in China. A cross-sectional questionnaire survey was conducted from January 10 to February 5, 2021 in Hangzhou city of Zhejiang Province, an eastern coastal province in China. The intention to accept COVID-19 vaccination and health beliefs based on the Health Belief Model were collected. Of the participants, college students reported the lowest COVID-19 vaccination intention (64.6%), followed by public transportation workers (72.4%) and health care workers (79.9%). Perceived barriers were identified as negative factors of vaccination intention among all three occupational groups. For college students and public transportation workers, perceived benefits and cues to action were identified as protective factors, and cues to action had a positive effect on vaccination intention of health care workers. Tailored interventions are encouraged to reduce barriers of vaccination, improve health beliefs and promote COVID-19 vaccination intentions.

Fatigue and Its Association With Quality of Life Among Carers of Patients Attending Psychiatric Emergency Services During the COVID-19 Pandemic.

Aims: Carers of psychiatric patients often suffered from mental and physical burden during the coronavirus disease 2019 (COVID-19) pandemic due to the lack of mental health services. This study investigated the pattern of fatigue and its association with quality of life (QOL) among the carers of patients attending psychiatric emergency services during the COVID-19 pandemic. Methods: In this cross-sectional study, carers of patients attending psychiatric emergency services during the COVID-19 pandemic were consecutively included. Fatigue, insomnia symptoms, depressive symptoms, and QOL were assessed with standardized instruments. Results: A total of 496 participants were included. The prevalence of fatigue was 44.0% (95% CI = 39.6-48.4%). Multivariate logistic regression analysis revealed that fatigue was positively associated with higher education level (OR = 1.92, P < 0.01) and more severe depressive (OR = 1.18, P < 0.01) and insomnia symptoms (OR = 1.11, P < 0.01). ANCOVA analysis revealed that the QOL was significantly lower in carers with fatigue compared with those without (P = 0.03). Conclusions: Fatigue was common among carers of patients attending psychiatric emergency services during the COVID-19 pandemic. Considering the adverse impact of fatigue on QOL and other health outcomes, routine screening and appropriate intervention for fatigue are warranted for this subpopulation.

SARS-CoV-2 infection in the mouse olfactory system.

SARS-CoV-2 infection causes a wide spectrum of clinical manifestations in humans, and olfactory dysfunction is one of the most predictive and common symptoms in COVID-19 patients. However, the underlying mechanism by which SARS-CoV-2 infection leads to olfactory disorders remains elusive. Herein, we demonstrate that intranasal inoculation with SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), not the olfactory bulb (OB), resulting in transient olfactory dysfunction in humanized ACE2 (hACE2) mice. The sustentacular cells and Bowman's gland cells in the OE were identified as the major target cells of SARS-CoV-2 before invasion into olfactory sensory neurons (OSNs). Remarkably, SARS-CoV-2 infection triggers massive cell death and immune cell infiltration and directly impairs the uniformity of the OE structure. Combined transcriptomic and quantitative proteomic analyses revealed the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptor (OR) genes in the OE from the infected animals. Overall, our mouse model recapitulates olfactory dysfunction in COVID-19 patients and provides critical clues for understanding the physiological basis for extrapulmonary manifestations of COVID-19.

Impact of socioeconomic status，population mobility and control measures on COVID-10 development in major cities of China.

:To evaluate the impact of socioeconomic status，population mobility，prevention and control measures on the early-stage coronavirus disease 2019 (COVID-19) development in major cities of China. : The rate of daily new confirmed COVID-19 cases in the 51 cities with the largest number of cumulative confirmed cases as of February 19，2020 (except those in Hubei province) were collected and analyzed using the time series cluster analysis. It was then assessed according to three aspects，that is, socioeconomic status，population mobility，and control measures for the pandemic. : According to the analysis on the 51 cities，4 development patterns of COVID-19 were obtained，including a high-incidence pattern (in Xinyu)，a late high-incidence pattern (in Ganzi)，a moderate incidence pattern (in Wenzhou and other 12 cities)，and a low and stable incidence pattern (in Hangzhou and other 35 cities). Cities with different types and within the same type both had different scores on the three aspects. : There were relatively large difference on the COVID-19 development among different cities in China，possibly affected by socioeconomic status，population mobility and prevention and control measures that were taken. Therefore，a timely public health emergency response and travel restriction measures inside the city can interfere the development of the pandemic. Population flow from high risk area can largely affect the number of cumulative confirmed cases.

Eating Habits and Lifestyles during the Initial Stage of the COVID-19 Lockdown in China: A Cross-Sectional Study.

Due to the outbreak of coronavirus disease 2019 (COVID-19), the Chinese government implemented strict lockdown measures to control the spread of infection. The impact of the COVID-19 lockdown on eating habits and lifestyles in the general population is unclear. This cross-sectional study was conducted via an online survey to obtain an overview of the food access, food intake, and physical activity of Chinese residents during the initial stage of the COVID-19 lockdown, and to investigate the association between staying at home/working from home and changes in eating habits and lifestyles. A total of 2702 participants (70.7% women) were included. Most of the participants maintained their habitual diet, while 38.2% increased their snack intake, 54.3% reported reduced physical activity, and 45.5% had increased sleep duration. Most people (70.1%) reported no change in body weight, while 25.0% reported an increase. Always staying at home/working from home was associated with an increase in animal product, vegetable, fruit, mushroom, nut, water, and snack intake, as well as sleep duration and frequency of skipping breakfast (odds ratio (OR) 1.54, 1.62, 1.58, 1.53, 1.57, 1.52, 1.77, 2.29, and 1.76 respectively). Suggestions should be made to encourage people to reduce their snack intake, maintain the daily consumption of breakfast, and increase physical activity during future lockdown periods.