Metagenomics of gut microbiome for migratory seagulls in Kunming city revealed the potential public risk to human health.

BACKGROUND: Seagull as a migratory wild bird has become most popular species in southwest China since 1980s. Previously, we analyzed the gut microbiota and intestinal pathogenic bacteria configuration for this species by using 16S rRNA sequencing and culture methods. To continue in-depth research on the gut microbiome of migratory seagulls, the metagenomics, DNA virome and RNA virome were both investigated for their gut microbial communities of abundance and diversity in this study. RESULTS: The metagenomics results showed 99.72% of total species was bacteria, followed by viruses, fungi, archaea and eukaryota. In particular, Shigella sonnei, Escherichia albertii, Klebsiella pneumonia, Salmonella enterica and Shigella flexneri were the top distributed taxa at species level. PCoA, NMDS, and statistics indicated some drug resistant genes, such as adeL, evgS, tetA, PmrF, and evgA accumulated as time went by from November to January of the next year, and most of these genes were antibiotic efflux. DNA virome composition demonstrated that Caudovirales was the most abundance virus, followed by Cirlivirales, Geplafuvirales, Petitvirales and Piccovirales. Most of these phages corresponded to Enterobacteriaceae and Campylobacteriaceae bacterial hosts respectively. Caliciviridae, Coronaviridae and Picornaviridae were the top distributed RNA virome at family level of this migratory animal. Phylogenetic analysis indicated the sequences of contigs of Gammacoronavirus and Deltacoronavirus had highly similarity with some coronavirus references. CONCLUSIONS: In general, the characteristics of gut microbiome of migratory seagulls were closely related to human activities, and multiomics still revealed the potential public risk to human health.

Mechanism of an RBM-targeted rabbit monoclonal antibody 9H1 neutralizing SARS-CoV-2.

The COVID-19 pandemic, caused by SARS-CoV-2, has led to over 750 million infections and 6.8 million deaths worldwide since late 2019. Due to the continuous evolution of SARS-CoV-2, many significant variants have emerged, creating ongoing challenges to the prevention and treatment of the pandemic. Therefore, the study of antibody responses against SARS-CoV-2 is essential for the development of vaccines and therapeutics. Here we perform single particle cryo-electron microscopy (cryo-EM) structure determination of a rabbit monoclonal antibody (RmAb) 9H1 in complex with the SARS-CoV-2 wild-type (WT) spike trimer. Our structural analysis shows that 9H1 interacts with the receptor-binding motif (RBM) region of the receptor-binding domain (RBD) on the spike protein and by directly competing with angiotensin-converting enzyme 2 (ACE2), it blocks the binding of the virus to the receptor and achieves neutralization. Our findings suggest that utilizing rabbit-derived mAbs provides valuable insights into the molecular interactions between neutralizing antibodies and spike proteins and may also facilitate the development of therapeutic antibodies and expand the antibody library.

Sound environment in an urban apartment building during and after the COVID-19 lockdown

Quiet areas, such as quiet communities, are encouraged to maintain a harmonious and peaceful urban living environment, and the design approach has drawn increasing attention in recent years. Related residential standards define the thresholds of quietness concerning noise pollution problems. However, the variations in height across floors of high-rise buildings and time in sound environments have not been detailed. The city of Shanghai experienced a citywide lockdown to contain the spread of COVID-19 showing the evidence of quietness with marked reductions in anthropogenic noise. Here, we conducted noise monitoring in a 14-story apartment building surrounded and shielded by other buildings in a typical urban community during and after lockdown. The mean value of the equivalent continuous A-weighted sound pressure level (LAeq) of all 14 floors after lockdown was higher than that during lockdown, and the differences were 3.6 and 3.1 dB during the daytime and night-time periods, respectively. The LAeq values at low heights were slightly lower than those at high heights during and after lockdown. The variations due to the different heights were not great. However, the change tendency from the ground to the top floors was similar and correlated during and after lockdown. The difference between the maximum and minimum values of the floors was 3 dB during the daytime period and 4.5 to 5.1 dB during the night-time period. The day equivalent continuous A-weighted sound pressure level (Lday) and night equivalent continuous A-weighted sound pressure level (Lnight) at the middle building height increased 4.0 and 1.3 dB, respectively, after lockdown. The LAeq change tendency during a daily cycle during and after lockdown was similar and highly correlated. The differences in the frequency characteristics of noise level were larger within the 63 to 2,000 Hz range. We suggest that the building represents a typical quiet living condition in high-density habitats in China. Notably, the difference is approximately 3 to 4 dB, and the patterns of variation in height and time are similar between the absence and limited presence of anthropogenic noise. In practice, it would be useful to consider specific floor level or time of day.

A SARS-CoV-2 neutralizing antibody discovery by single cell sequencing and molecular modeling.

Although vaccines have been developed, mutations of SARS-CoV-2, especially the dominant B.1.617.2 (delta) and B.1.529 (omicron) strains with more than 30 mutations on their spike protein, have caused a significant decline in prophylaxis, calling for the need for drug improvement. Antibodies are drugs preferentially used in infectious diseases and are easy to get from immunized organisms. The current study combined molecular modeling and single memory B cell sequencing to assess candidate sequences before experiments, providing a strategy for the fabrication of SARS-CoV-2 neutralizing antibodies. A total of 128 sequences were obtained after sequencing 196 memory B cells, and 42 sequences were left after merging extremely similar ones and discarding incomplete ones, followed by homology modeling of the antibody variable region. Thirteen candidate sequences were expressed, of which three were tested positive for receptor binding domain recognition but only one was confirmed as having broad neutralization against several SARS-CoV-2 variants. The current study successfully obtained a SARS-CoV-2 antibody with broad neutralizing abilities and provided a strategy for antibody development in emerging infectious diseases using single memory B cell BCR sequencing and computer assistance in antibody fabrication.

Effects of coronavirus disease 2019 vaccination on seizures in patients with epilepsy.

BACKGROUND: Given that seizures may be triggered by vaccination, this study aimed to evaluate the risk and correlative factors of seizures in patients with epilepsy (PWE) after being vaccinated against coronavirus disease 2019 (COVID-19). METHODS: This study retrospectively enrolled PWE who were vaccinated against COVID-19 in the epilepsy centers of 11 hospitals in China. We divided the PWE into two groups as follows: (1) patients who developed seizures within 14 days of vaccination were assigned to the SAV (with seizures after vaccination) group; (2) patients who were seizure-free within 14 days of vaccination were assigned to the SFAV (seizure-free after vaccination) group. To identify potential risk factors for seizure reccurence, the binary logistic regression analysis was performed. Besides, 67 PWE who had not been vaccinated were also included for elucidating the effects of vaccination on seizures recurrence, and binary logistic regression analysis was performed to determine whether vaccination would affect the recurrence rate of PWE who had drug reduction or withdrawal. RESULTS: The study included a total of 407 patients; of which, 48 (11.8%) developed seizures within 14 days after vaccination (SAV group), whereas 359 (88.2%) remained seizure-free (SFAV group). The binary logistic regression analysis revealed that duration of seizure freedom ( P  < 0.001) and withdrawal from anti-seizure medications (ASMs) or reduction in their dosage during the peri-vaccination period were significantly associated with the recurrence of seizures (odds ratio = 7.384, 95% confidence interval = 1.732-31.488, P  = 0.007). In addition, 32 of 33 patients (97.0%) who were seizure-free for more than three months before vaccination and had a normal electroencephalogram before vaccination did not have any seizures within 14 days of vaccination. A total of 92 (22.6%) patients experienced non-epileptic adverse reactions after vaccination. Binary logistic regression analysis results showed that vaccine did not significantly affect the recurrence rate of PWE who had the behavior of ASMs dose reduction or withdrawal ( P  = 0.143). CONCLUSIONS: PWE need protection from the COVID-19 vaccine. PWE who are seizure-free for >3 months before vaccination should be vaccinated. Whether the remaining PWE should be vaccinated depends on the local prevalence of COVID-19. Finally, PWE should avoid discontinuing ASMs or reducing their dosage during the peri-vaccination period.

Kaempferol has potential anti-coronavirus disease 2019 (COVID-19) targets based on bioinformatics analyses and pharmacological effects on endotoxin-induced cytokine storm.

COVID-19 has infected 272 million patients and caused 5.33 million deaths around the world, and it remains the main global threat. Previous studies revealed that Chinese traditional medicine is an effective treatment for COVID-19 infection. This study aims to reveal the pharmacological effects of kaempferol, which is the active component of Radix Bupleuri and Tripterygii Radix, and potential mechanisms for the treatment of COVID-19. Here, we employed the bioinformatics methods to filter the anti-COVID-19 candidate genes of kaempferol, which mainly enriched in inflammation (TNF, JUN, etc.) and virus infection (AKT1, JNK, etc.). The Transcription levels of AKT1, JNK and JUN were significantly reduced by kaempferol treatment in the LPS-activated macrophages. In addition, kaempferol reduced the secretion of inflammatory factors by LPS-stimulated macrophages, inhibited MAPK/NF-κB signaling and regulated macrophage polarization to M2 type in vitro, and suppressed endotoxin-induced cytokine storm and improved survival in mice. Molecular docking analysis demonstrated that kaempferol was probable to bind the COVID-19 protein 5R84 and formatted hydrogen bond with the residues, the free binding energy of which was lower than the original ligand. In summary, our current work indicates that kaempferol has anti-COVID-19 potential through the reduction of COVID-19-induced body dysfunction and molecule-protein interaction, and bioinformatics results clarify that some of these key target genes might serve as potential molecular markers for detecting COVID-19.

Effect of inactivated COVID-19 vaccines on seizure frequency in patients with epilepsy: A multicenter, prospective study.

Objectives: Several COVID-19 vaccines list "uncontrolled epilepsy" as a contraindication for vaccination. This consequently restricts vaccination against COVID-19 in patients with epilepsy (PWE). However, there is no strong evidence that COVID-19 vaccination can exacerbate conditions in PWE. This study aims to determine the impact of COVID-19 vaccination on PWE. Methods: PWE were prospectively recruited from 25 epilepsy centers. We recorded the seizure frequency at three time periods (one month before the first vaccination and one month after the first and second vaccinations). A generalized linear mixed-effects model (GLMM) was used for analysis, and the adjusted incidence rate ratio (AIRR) with 95% CI was presented and interpreted accordingly. Results: Overall, 859 PWE were included in the analysis. Thirty-one (3.6%) and 35 (4.1%) patients were found to have increased seizure frequency after the two doses, respectively. Age had an interaction with time. The seizure frequency in adults decreased by 81% after the first dose (AIRR=0.19, 95% CI:0.11-0.34) and 85% after the second dose (AIRR=0.16, 95% CI:0.08-0.30). In juveniles (<18), it was 25% (AIRR=0.75, 95% CI:0.42-1.34) and 51% (AIRR=0.49, 95% CI:0.25-0.95), respectively. Interval between the last seizure before vaccination and the first dose of vaccination (ILSFV) had a significant effect on seizure frequency after vaccination. Seizure frequency in PWE with hereditary epilepsy after vaccination was significantly higher than that in PWE with unknown etiology (AIRR=1.95, 95% CI: 1.17-3.24). Two hundred and seventeen (25.3%) patients experienced non-epileptic but not serious adverse reactions. Discussion: The inactivated COVID-19 vaccine does not significantly increase seizure frequency in PWE. The limitations of vaccination in PWE should focus on aspects other than control status. Juvenile PWE should be of greater concern after vaccination because they have lower safety. Finally, PWE should not reduce the dosage of anti-seizure medication during the peri-vaccination period.

Safety and immunogenicity of inactivated COVID-19 vaccination in adult rheumatic patients in South China: a prospective study.

Patients with rheumatic diseases (RD) are considered to be a high-risk population for infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The effectiveness of inactivated COVID-19 vaccinations (ICVs) was described as more effective than 95%. Despite this, no data on the immunogenicity and safety of the ICV in Han race stable RD patients in China. In this study, we sought to assess the safety and immunogenicity of the ICVs in RD patients in South China. A total of 80 adult stable RD patients were recruited. Following 14-35 days of immunization, cheiluminescence immunoassays (CLIA) were utilized to detect antibodies titers. An investigation into the relative parameters on the immunogenicity response to vaccination was carried out using logistic regression analysis. Compared to the HC group, the positive response of IgG and Nab in RD patients were lower than those in healthy control (HC) (P = .040 and P < .0001, respectively) after two doses of ICV were inoculated. The use of methotrexate (P = .016) and prednisolone (P = .018), and the level of red blood cell distribution width-C (RDW-C) (P = .035) and C-reactive protein (P = .015) were independently associated with lower rises in the magnitude of COVID-19 vaccine antibodies. No vaccine-related serious adverse reactions were observed in either group. After receiving two doses of ICVs, the production of protective antibodies in stable RD patients treated with immunosuppressive agents may decrease. It was discovered that ICVs were safe and well tolerated by RD patients.

What is the context?There are currently no accessible data on the efficacy and safety of inactivated COVID-19 vaccinations in South China RD patients who are receiving immunosuppressive medications.What is new?Inactivated COVID-19 vaccinations were immunogenic in stable RD patients in our investigation. No significant adverse reactions to the vaccination were seen in either group. No disease flares were observed in our study.What is the impact?Inactivated COVID-19 vaccinations are immunogenic and safe in stable RD patients in China, according to the findings of this study. The use of methotrexate or prednisolone, the RDW-C level, and the CRP level may all have an effect on the development of protective antibodies following vaccination.

Structures of Omicron spike complexes and implications for neutralizing antibody development.

The emergence of the SARS-CoV-2 Omicron variant is dominant in many countries worldwide. The high number of spike mutations is responsible for the broad immune evasion from existing vaccines and antibody drugs. To understand this, we first present the cryo-electron microscopy structure of ACE2-bound SARS-CoV-2 Omicron spike. Comparison to previous spike antibody structures explains how Omicron escapes these therapeutics. Secondly, we report structures of Omicron, Delta, and wild-type spikes bound to a patient-derived Fab antibody fragment (510A5), which provides direct evidence where antibody binding is greatly attenuated by the Omicron mutations, freeing spike to bind ACE2. Together with biochemical binding and 510A5 neutralization assays, our work establishes principles of binding required for neutralization and clearly illustrates how the mutations lead to antibody evasion yet retain strong ACE2 interactions. Structural information on spike with both bound and unbound antibodies collectively elucidates potential strategies for generation of therapeutic antibodies.

Timeliness of information disclosure during the low transmission period of COVID-19: resident-level observational study in China.

BACKGROUND: Only when people feel they have received timely disclosure will they have sufficient incentive to implement community prevention and control measures. The timely and standardized information published by authorities as a response to the crisis can better inform the public and enable better preparations for the pandemic during the low transmission period of COVID-19; however, there is limited evidence of whether people consent that information is disclosed timely and influencing factors. METHODS: A cross-sectional survey was conducted in China from 4 to 26 February 2021. Convenient sampling strategy was adopted to recruit participators. Participants were asked to filled out the questions that assessed questionnaire on the residents' attitudes to information disclosure timely. A binary logistic regression analysis was performed to identify the risk factors affecting the residents' attitudes. RESULTS: A total of 2361 residents filled out the questionnaire. 1704 (72.17%) consented COVID-19 information has been disclosed timely. Furthermore, age (OR = 0.093, 95%CI = 0.043 ~ 0.201), gender (OR = 1.396, 95%CI = 1.085 ~ 1.797), place of residence (OR = 0.650, 95%CI = 0.525 ~ 0.804), employed status (OR = 2.757, 95%CI = 1.598 ~ 4.756), highest educational level (OR = 0.394, 95%CI = 0.176 ~ 0.880), region (OR = 0.561, 95%CI = 0.437 ~ 0.720) and impact on life by the COVID-19 (OR = 0.482, 95%CI = 0.270 ~ 0.861) were mainly factors associated with residents' attitudes. CONCLUSIONS: The aims of this study were to evaluate the residents attitudes to information disclosure timely during the low transmission period in China and to provide a scientific basis for effective information communication in future public health crises. Timely and effective efforts to disclose information need to been made during the low transmission period. Continued improvements to local authority reporting will contribute to more effective public communication and efficient public health research responses. The development of protocols and the standardization of epidemic message templates-as well as the use of uniform operating procedures to provide regular information updates-should be prioritized to ensure a coordinated national response.

Molecular Mechanism of SARS-CoVs Orf6 Targeting the Rae1-Nup98 Complex to Compete With mRNA Nuclear Export.

The accessory protein Orf6 is uniquely expressed in sarbecoviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is an ongoing pandemic. SARS-CoV-2 Orf6 antagonizes host interferon signaling by inhibition of mRNA nuclear export through its interactions with the ribonucleic acid export 1 (Rae1)-nucleoporin 98 (Nup98) complex. Here, we confirmed the direct tight binding of Orf6 to the Rae1-Nup98 complex, which competitively inhibits RNA binding. We determined the crystal structures of both SARS-CoV-2 and SARS-CoV-1 Orf6 C-termini in complex with the Rae1-Nup98 heterodimer. In each structure, SARS-CoV Orf6 occupies the same potential mRNA-binding groove of the Rae1-Nup98 complex, comparable to the previously reported structures of other viral proteins complexed with Rae1-Nup98, indicating that the Rae1-Nup98 complex is a common target for different viruses to impair the nuclear export pathway. Structural analysis and biochemical studies highlight the critical role of the highly conserved methionine (M58) of SARS-CoVs Orf6. Altogether our data unravel a mechanistic understanding of SARS-CoVs Orf6 targeting the mRNA-binding site of the Rae1-Nup98 complex to compete with the nuclear export of host mRNA, which further emphasizes that Orf6 is a critical virulence factor of SARS-CoVs.

Attitudes to Being Vaccinated Against COVID-19: A Survey of People With Epilepsy in China.

Objective: We conducted a survey to assess vaccination coverage, vaccination willingness, and variables associated with vaccination hesitancy to provide evidence on coronavirus disease (COVID-19) vaccination strategies. Methods: This anonymous questionnaire study conducted a multicenter, cross-sectional survey of outpatients and inpatients with epilepsy (PWE) registered in epilepsy clinics, in 2021, in 10 hospitals in seven cities of Shandong Province. Results: A total of 600 questionnaires were distributed, and 557 valid questionnaires were returned. A total of 130 people were vaccinated against COVID-19. Among 427 unvaccinated participants, 69.32% (296/427) were willing to receive the COVID-19 vaccine in the future, and the remaining 30.68% (131/427) were unwilling to receive vaccination. Most (89.9%) of the participants believed that the role of vaccination was crucial in response to the spread of COVID-19. A significant association was found between willingness to receive the COVID-19 vaccine and the following variables: age, marital status, level of education, occupation, residence, seizure type, and seizure control after antiepileptic drug therapy. It is noteworthy that education level, living in urban areas, and seizure freedom were significantly related to willingness to receive COVID-19 vaccination. Conclusions: Vaccination is a key measure for the prevention and control of COVID-19, and most PWE are willing to be vaccinated. Vaccine safety, effectiveness, and accessibility are essential in combatting vaccine hesitation and increasing vaccination rates.

Semen quality and windows of susceptibility: A case study during COVID-19 outbreak in China.

BACKGROUND: To evaluate the impact of air pollution exposure on semen quality parameters during COVID-19 outbreak in China, and to identify potential windows of susceptibility for semen quality. METHODS: A retrospective observational study was carried out on 1991 semen samples collected between November 23, 2019 and July 23, 2020 (a period covering COVID-19 lock-down in China) from 781 sperm donor candidates at University-affiliated Sichuan Provincial Human Sperm Bank. Multivariate mixed-effects regression models were constructed to investigate the relationship between pollution exposure, windows of susceptibility, and semen quality, while controlling for biographic and meteorologic confounders. RESULT(S): The results indicated multiple windows of susceptibility for semen quality, especially sperm motility, due to ambient pollution exposure. Exposure to particulate matters (PM2.5 and PM10), O3 and NO2 during late stages of spermatogenesis appeared to have weak but positive association with semen quality. Exposure to CO late in sperm development appeared to have inverse relationship with sperm movement parameters. Exposure to SO2 appeared to influence semen quality throughout spermatogenesis. CONCLUSION(S): Potential windows of susceptibility for semen quality varied depending on air pollutants. Sperm motility was sensitive to pollution exposure. Findings from current study further elucidate the importance of sensitive periods during spermatogenesis and provide new evidence for the determinants of male fertility.

Analysis on the Characteristics of Air Pollution in China during the COVID-19 Outbreak

The COVID-19 pandemic poses a serious global threat to human health. In China, the government immediately implemented lockdown measures to curb the spread of this virus. These measures severely affected transportation and industrial production across the country, resulting in a significant change in the concentration of air pollutants. In this study, the Euclidean distance method was used to select the most similar meteorological field during the COVID-19 lockdown period. Changes in the concentration of air pollutants in China were analyzed under similar meteorological background conditions. Results indicate that, compared with data from 2015–2019, air quality in China significantly improved;with the exception of ozone (O3), the concentration of major air pollutants declined. Compared with baseline conditions, the reduction of air pollutants in China from 25 January to 22 February 2020 (Period 2) was the most significant. In particular, NO2 decreased by 41.7% in the Yangtze River Delta. In Period 2, the reduction of air pollutants in areas other than Hubei gradually decreased, but the reduction of NO2 in Wuhan reached 61.92%, and the reduction of air pollutants in various regions after February 23 was significantly reduced. By excluding the influence of meteorological factors and calculating the contribution of human activities to atmospheric pollutants by linear fitting, in Period 2 the effect of artificial controls on NO2 in Wuhan attained 30.66%, and reached 48.17% from 23 February to 23 March (Period 3). Results from this investigation provides effective theoretical support for pollution prevention and control in China.