A 10-valent composite mRNA vaccine against both influenza and COVID-19 (preprint)

The COVID-19 pandemic caused by SARS-CoV-2 viruses has had a persistent and significant impact on global public health for four years. Recently, there has been a resurgence of seasonal influenza transmission worldwide. The co-circulation of SARS-CoV-2 and seasonal influenza viruses results in a dual burden on communities. Additionally, the pandemic potential of zoonotic influenza viruses, such as avian Influenza A/H5N1 and A/H7N9, remains a concern. Therefore, a combined vaccine against all these respiratory diseases is in urgent need. mRNA vaccines, with their superior efficacy, speed in development, flexibility, and cost-effectiveness, offer a promising solution for such infectious diseases and potential future pandemics. In this study, we present FLUCOV-10, a novel 10-valent mRNA vaccine created from our proven platform. This vaccine encodes hemagglutinin (HA) proteins from four seasonal influenza viruses and two avian influenza viruses with pandemic potential, as well as spike proteins from four SARS-CoV-2 variants. A two-dose immunization with the FLUCOV-10 elicited robust immune responses in mice, producing IgG antibodies, neutralizing antibodies, and antigen-specific cellular immune responses against all the vaccine-matched viruses of influenza and SARS-CoV-2. Remarkably, the FLUCOV-10 immunization provided complete protection in mouse models against both homologous and heterologous strains of influenza and SARS-CoV-2. These results highlight the potential of FLUCOV-10 as an effective vaccine candidate for the prevention of influenza and COVID-19.

Functional Foods: A Promising Strategy for Restoring Gut Microbiota Diversity Impacted by SARS-CoV-2 Variants (preprint)

Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked with en-hanced immunity, regeneration, improved cognitive function, maintenance of gut mi-crobiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because the respiratory and gastrointestinal tracts are rich in microbial diversity and contain high ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity and the potential use of functional foods as a strategy to combat these effects.

Wearing Masks Implies Refuting Trump?: Towards Target-specific User Stance Prediction across Events in COVID-19 and US Election 2020 (preprint)

People who share similar opinions towards controversial topics could form an echo chamber and may share similar political views toward other topics as well. The existence of such connections, which we call connected behavior, gives researchers a unique opportunity to predict how one would behave for a future event given their past behaviors. In this work, we propose a framework to conduct connected behavior analysis. Neural stance detection models are trained on Twitter data collected on three seemingly independent topics, i.e., wearing a mask, racial equality, and Trump, to detect people's stance, which we consider as their online behavior in each topic-related event. Our results reveal a strong connection between the stances toward the three topical events and demonstrate the power of past behaviors in predicting one's future behavior.

An investigation of the incidence of post-traumatic stress disorder, turnover intention and psychological resilience among medical staff in a public hospital in China during the outbreak of the omicron variant in the COVID-19 pandemic in 2022.

Objective: To investigate the incidence of post-traumatic stress disorder (PTSD), turnover intention and psychological resilience of medical staff during the Outbreak of the Omicron Variant in the COVID-19 pandemic in 2022 and to provide a basis for adopting relevant psychological interventions to reduce medical staff turnover. Methods: Using the PTSD Checklist-Civilian Version (PCL-C) and a total score ranging from 17 to 85 points, a total score ≥ 38 indicates significant PTSD symptoms and a diagnosis of PTSD. The Chinese version of the Turnover Intention Scale (TIS) has a total score of 6 to 24 points; the higher the score, the stronger the turnover intention. The Chinese version of the Connor-Davidson Resilience Scale (CD-RISC) has a total score of 0 to 100 points, with higher scores indicating a better level of psychological resilience. A total of 443 front-line medical staff working in Chinese public hospitals and still treating all patients normally during COVID-19 were invited via the internet to complete a survey from 15 May to 30 May 2022 in China. Results: The incidence of PTSD was 14.4%, the total turnover intention score was 13.38 ± 4.08, and the total psychological resilience score was 87.16 ± 18.42. The prevalence of PTSD was higher among medical staff who were married, had children, and were worried about being infected; in addition, the PTSD group had a higher level of education, higher turnover intention, and lower psychological resilience than the non-PTSD group. The total scores for turnover intention and fear of being infected were risk factors for PTSD, while a high total psychological resilience score and high education level were protective factors for PTSD; the differences were statistically significant (all P < 0.05). Conclusion: Post-traumatic stress disorder among Chinese medical personnel was associated with the marital status, childbirth, education level, turnover intention, and psychological resilience. Among these factors, psychological resilience might be exploited as a protective factor.

Analysis of Online Education Reviews of Universities Using NLP Techniques and Statistical Methods

In the long-running battle against COVID-19, it is worth further discussing how well online education is accepted by users as a new type of education method which is popularized suddenly. The launch of a large-scale online teaching during the COVID-19 pandemic gave us the opportunity to investigate the opinions and emotions of online teaching users. This paper employs NLP techniques and statistical methods to process 93754 comments collected from the three online teaching platforms designated by the Ministry of Education for universities. This study aims to gain a better understanding of the changing characteristics of students’ opinions and emotions regarding online teaching, as well as to learn what students required and how the platforms functioned during the epidemic period. The findings revealed that (1) users of online teaching platforms were mostly concerned about whether the teaching resources provided by the platforms were rich and of high quality all along. The main influencing factors affecting online teaching experiences during the implementation of large-scale online teaching are hardware device deficiencies such as server congestion and network lag. (2) The majority of users expressed positive attitude towards online education which played a positive role during the outbreak. (3) The epidemic had a significant impact on the emotions of online teaching users. In short, the research themes showed that online teaching users are always concerned with the richness and quality of the platform’s resources. Furthermore, the most important issues for users during the period of large-scale online teaching are whether the network infrastructure is efficient and smooth, as well as the platform’s function perfection. The popularity of online teaching helped to solidify the online teaching space and improve its social image. This study provides a point of reference for the development and improvement of online education and compensates for a lack of relevant studies.

Ultraminiature optical fiber-tip directly-printed plasmonic biosensors for label-free biodetection

Miniaturization of biosensors has become an imperative demand because of its great potential in in vivo biomarker detection and disease diagnostics as well as the point-of-care testing for coping with public health crisis, such as the coronavirus disease 2019 pandemic. Here, we present an ultraminiature optical fiber-tip biosensor based on the plasmonic gold nanoparticles (AuNPs) directly printed upon the end face of a standard multimode optical fiber at visible light range. An in-situ precision photoreduction technology is developed to additively print the micropatterns of size-controlled AuNPs. The AuNPs reveal distinct localized surface plasmon resonance, whose peak wavelength provides an ideal spectral signal for label-free biodetection. The fabricated optical fiber-tip plasmonic biosensor can not only detect antibody, but also test SARS-CoV-2 mimetic DNA sequence at the concentration level of 0.8 pM. Such an ultraminiature fiber-tip plasmonic biosensor offers a cost-effective biodetection technology for a myriad of applications ranging from point-of-care testing to in vivo diagnosis of stubborn diseases.

Genetic engineering of baculovirus-insect cell system to improve protein production

The Baculovirus Expression Vector System (BEVS), a mature foreign protein expression platform, has been available for decades, and has been effectively used in vaccine production, gene therapy, and a host of other applications. To date, eleven BEVS-derived products have been approved for use, including four human vaccines [Cervarix against cervical cancer caused by human papillomavirus (HPV), Flublok and Flublok Quadrivalent against seasonal influenza, Nuvaxovid/Covovax against COVID-19], two human therapeutics [Provenge against prostate cancer and Glybera against hereditary lipoprotein lipase deficiency (LPLD)] and five veterinary vaccines (Porcilis Pesti, BAYOVAC CSF E2, Circumvent PCV, Ingelvac CircoFLEX and Porcilis PCV). The BEVS has many advantages, including high safety, ease of operation and adaptable for serum-free culture. It also produces properly folded proteins with correct post-translational modifications, and can accommodate multi-gene– or large gene insertions. However, there remain some challenges with this system, including unstable expression and reduced levels of protein glycosylation. As the demand for biotechnology increases, there has been a concomitant effort into optimizing yield, stability and protein glycosylation through genetic engineering and the manipulation of baculovirus vector and host cells. In this review, we summarize the strategies and technological advances of BEVS in recent years and explore how this will be used to inform the further development and application of this system.

An investigation of the incidence of post-traumatic stress disorder, turnover intention and psychological resilience among medical staff in a public hospital in China during the outbreak of the omicron variant in the COVID-19 pandemic in 2022

Objective To investigate the incidence of post-traumatic stress disorder (PTSD), turnover intention and psychological resilience of medical staff during the Outbreak of the Omicron Variant in the COVID-19 pandemic in 2022 and to provide a basis for adopting relevant psychological interventions to reduce medical staff turnover. Methods Using the PTSD Checklist-Civilian Version (PCL-C) and a total score ranging from 17 to 85 points, a total score ≥ 38 indicates significant PTSD symptoms and a diagnosis of PTSD. The Chinese version of the Turnover Intention Scale (TIS) has a total score of 6 to 24 points;the higher the score, the stronger the turnover intention. The Chinese version of the Connor-Davidson Resilience Scale (CD-RISC) has a total score of 0 to 100 points, with higher scores indicating a better level of psychological resilience. A total of 443 front-line medical staff working in Chinese public hospitals and still treating all patients normally during COVID-19 were invited via the internet to complete a survey from 15 May to 30 May 2022 in China. Results The incidence of PTSD was 14.4%, the total turnover intention score was 13.38 ± 4.08, and the total psychological resilience score was 87.16 ± 18.42. The prevalence of PTSD was higher among medical staff who were married, had children, and were worried about being infected;in addition, the PTSD group had a higher level of education, higher turnover intention, and lower psychological resilience than the non-PTSD group. The total scores for turnover intention and fear of being infected were risk factors for PTSD, while a high total psychological resilience score and high education level were protective factors for PTSD;the differences were statistically significant (all P < 0.05). Conclusion Post-traumatic stress disorder among Chinese medical personnel was associated with the marital status, childbirth, education level, turnover intention, and psychological resilience. Among these factors, psychological resilience might be exploited as a protective factor.

Semantic Cues Modulate Children’s and Adults’ Processing of Audio-Visual Face Mask Speech

During the COVID-19 pandemic, questions have been raised about the impact of face masks on communication in classroom settings. However, it is unclear to what extent visual obstruction of the speaker’s mouth or changes to the acoustic signal lead to speech processing difficulties, and whether these effects can be mitigated by semantic predictability, i.e., the availability of contextual information. The present study investigated the acoustic and visual effects of face masks on speech intelligibility and processing speed under varying semantic predictability. Twenty-six children (aged 8-12) and twenty-six adults performed an internet-based cued shadowing task, in which they had to repeat aloud the last word of sentences presented in audio-visual format. The results showed that children and adults made more mistakes and responded more slowly when listening to face mask speech compared to speech produced without a face mask. Adults were only significantly affected by face mask speech when both the acoustic and the visual signal were degraded. While acoustic mask effects were similar for children, removal of visual speech cues through the face mask affected children to a lesser degree. However, high semantic predictability reduced audio-visual mask effects, leading to full compensation of the acoustically degraded mask speech in the adult group. Even though children did not fully compensate for face mask speech with high semantic predictability, overall, they still profited from semantic cues in all conditions. Therefore, in classroom settings, strategies that increase contextual information such as building on students’ prior knowledge, using keywords, and providing visual aids, are likely to help overcome any adverse face mask effects.

Re-emergence of Severe Acute Diarrhea Syndrome Coronavirus (SADS-CoV) in Guangxi, China, 2021 (preprint)

Severe acute diarrhea syndrome coronavirus (SADS-CoV) has had a major impact on the swine industry in China, but has not been detected since 2019. Using real-time qPCR and metagenomic surveillance we identified SADS-CoV in a pig farm experiencing diarrheal disease. Genomic analysis supported the undetected circulation of SADS-CoV since 2019.

Cuffless and Touchless Measurement of Blood Pressure from Ballistocardiogram Based on a Body Weight Scale

Currently, in terms of reducing the infection risk of the COVID-19 virus spreading all over the world, the development of touchless blood pressure (BP) measurement has potential benefits. The pulse transit time (PTT) has a high relation with BP, which can be measured by electrocardiogram (ECG) and photoplethysmogram (PPG). The ballistocardiogram (BCG) reflects the mechanical vibration (or displacement) caused by the heart contraction/relaxation (or heart beating), which can be measured from multiple degrees of the body. The goal of this study is to develop a cuffless and touchless BP-measurement method based on a commercial weight scale combined with a PPG sensor when measuring body weight. The proposed method was that the PTTBCG-PPGT was extracted from the BCG signal measured by a weight scale, and the PPG signal was measured from the PPG probe placed at the toe. Four PTT models were used to estimate BP. The reference method was the PTTECG-PPGF extracted from the ECG signal and PPG signal measured from the PPG probe placed at the finger. The standard BP was measured by an electronic blood pressure monitor. Twenty subjects were recruited in this study. By the proposed method, the root-mean-square error (ERMS) of estimated systolic blood pressure (SBP) and diastolic blood pressure (DBP) are 6.7 ±1.60 mmHg and 4.8 ±1.47 mmHg, respectively. The correlation coefficients, r2, of the proposed model for the SBP and DBP are 0.606 ±0.142 and 0.284 ±0.166, respectively. The results show that the proposed method can serve for cuffless and touchless BP measurement.

Low-rank Latent Matrix-factor Prediction Modeling for Generalized High-dimensional Matrix-variate Regression (preprint)

Motivated by diagnosing the COVID-19 disease using 2D image biomarkers from computed tomography (CT) scans, we propose a novel latent matrix-factor regression model to predict responses that may come from an exponential distribution family, where covariates include high-dimensional matrix-variate biomarkers. A latent generalized matrix regression (LaGMaR) is formulated, where the latent predictor is a low-dimensional matrix factor score extracted from the low-rank signal of the matrix variate through a cutting-edge matrix factor model. Unlike the general spirit of penalizing vectorization plus the necessity of tuning parameters in the literature, instead, our prediction modeling in LaGMaR conducts dimension reduction that respects the geometry characteristic of intrinsic two-dimensional structure of the matrix covariate and thus avoids iteration. This greatly relieves the computation burden, and meanwhile maintains structural information so that the latent matrix factor feature can perfectly replace the intractable matrix-variate owing to high-dimensionality. The estimation procedure of LaGMaR is subtly derived by transforming the bilinear form matrix factor model onto a high-dimensional vector factor model, so that the method of principle components can be applied. We establish bilinear-form consistency of the estimated matrix coefficient of the latent predictor and consistency of prediction. The proposed approach can be implemented conveniently. Through simulation experiments, prediction capability of LaGMaR is shown to outperform existing penalized methods under diverse scenarios of generalized matrix regressions. Through the application to a real COVID-19 dataset, the proposed approach is shown to predict efficiently the COVID-19.

Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2 (preprint)

Background The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social. The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health and economic stability worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19.Methods We first established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus S protein and its host receptor ACE2. Two compound libraries of 2,864 molecules were screened with this platform. Selected candidate compounds were validated by SARS-CoV-2_S pseudotyped lentivirus and ACE2-overexpressing cell system. Molecular docking was used to analyze the interaction between S-protein and compounds.Results We identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S-protein and the human cell ACE2 receptor. Additionally, tannic acid showed moderate inhibitory effect on the interaction of S-protein and ACE2.Conclusion This platform is a rapid, sensitive, specific, and high throughput system, and available for screening large compound libraries. TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.

The Different Impacts of Emissions and Meteorology on PM2.5 Changes in Various Regions in China: A Case Study

Emissions and meteorology are significant factors affecting aerosol pollution, but it is not sufficient to understand their relative contributions to aerosol pollution changes. In this study, the observational data and the chemical model (GRAPES_CUACE) are combined to estimate the drivers of PM2.5 changes in various regions (the Beijing–Tianjin–Hebei (BTH), the Central China (CC), the Yangtze River Delta (YRD), and the Pearl River Delta (PRD)) between the first month after COVID-19 (FMC_2020) (i.e., from 23 January to 23 February 2020) and the corresponding period in 2019 (FMC_2019). The results show that PM2.5 mass concentration increased by 26% (from 61 to 77 µg m−3) in the BTH, while it decreased by 26% (from 94 to 70 µg m−3) in the CC, 29% (from 52 to 37 µg m−3) in the YRD, and 32% (from 34 to 23 µg m−3) in the PRD in FMC_2020 comparing with FMC_2019, respectively. In the BTH, although emissions reductions partly improved PM2.5 pollution (−5%, i.e., PM2.5 mass concentration decreased by 5% due to emissions) in FMC_2020 compared with that of FMC_2019, the total increase in PM2.5 mass concentration was dominated by more unfavorable meteorological conditions (+31%, i.e., PM2.5 mass concentration increased by 31% due to meteorology). In the CC and the YRD, emissions reductions (−33 and −36%) played a dominating role in the total decrease in PM2.5 in FMC_2020, while the changed meteorological conditions partly worsened PM2.5 pollution (+7 and +7%). In the PRD, emissions reductions (−23%) and more favorable meteorological conditions (−9%) led to a total decrease in PM2.5 mass concentration. This study reminds us that the uncertainties of relative contributions of meteorological conditions and emissions on PM2.5 changes in various regions are large, which is conducive to policymaking scientifically in China.

Ludangshen Oral Liquid for Treatment of Convalescent COVID-19 Patients: A Randomized, Double-Blind, Placebo-Controlled Multicenter Trial (preprint)

Objective To explore the effect of Ludangshen Oral Liquid for treatment of convalescent patients with coronavirus disease 2019 (COVID-19) with randomized, double-blind, placebo-controlled multicenter method.Methods200 convalescent COVID-19 patients who had symptoms related to decreased digestive and respiratory function were randomly divided to either receive Ludangshen Oral Liquid or placebo for 2 weeks. The severity of clinical symptoms including fatigue, anorexia, abdominal distension, loose stools, and shortness of breath were assessed by visual analogue scale and observed at before and after treatment. The improvement and resolution rates of clinical symptoms were evaluated. Full analysis set (FAS) and per-protocol set (PPS) were used for statistical analyses. Adverse events were recorded during the study. Results8 patients did not complete the study. After 2 weeks of treatment, both FAS and PPS results showed that patients in Ludangshen group had significantly lower score of fatigue, anorexia, loose stools, and shortness of breath than placebo group (P < 0.05), while there was no significant difference in distention (P > 0.05). The improvement rate of fatigue, anorexia, distension, loose stools and shortness of breath were significantly higher in Ludangshen group (P < 0.05), as well as the resolution rates (P < 0.05) except for shortness of breath (P > 0.05). There were two cases of adverse events, with one nose bleeding in Ludangshen group and one headache in placebo group. ConclusionThe study suggested that two weeks of Ludangshen Oral Liquid treatment may have certain effects for convalescent COVID-19 patients on improving digestive and respiratory symptoms including fatigue, anorexia, loose stools and shortness of breath, which may be one of the choices for management of convalescent COVID-19 patients with digestive and respiratory symptoms.

Immunosuppression impaired the immunogenicity of inactivated SARS-CoV-2 vaccine in non-dialysis kidney disease patients (preprint)

Patients with chronic kidney disease (CKD) are at higher risk for coronavirus disease 2019 (COVID-19)-related morbidity and mortality. However, a significant portion of CKD patients showed hesitation toward vaccination in telephone survey of our center. Yet no serial data available on humoral response in patients with CKD, especially those on immunosuppression. We conducted a pilot, prospective study to survey the safety and humoral response to inactivated SARS-CoV-2 vaccine in CKD patients receiving a 2-dose immunization of inactivated SARS-CoV-2 vaccine. We found the neutralizing antibody titers in CKD patients was significantly lower than that in healthy controls, hypertension patients, and diabetes patients. Notably, immunosuppressive medication rather than eGFR levels or disease types showed effect on the reduction of immunogenicity. Interestingly, a third dose significantly boosted neutralizing antibody in CKD patients while immunosuppressants impeded the boosting effects. In conclusion, our data demonstrates that CKD patients, even for those on immunosuppression treatment, can benefit from a third vaccination boost by improving their humoral immunity.

Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2 (preprint)

ABSTRACT The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social and economic stability. In this study, we established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus S protein and its host receptor ACE2. This platform is a rapid, sensitive, specific, and high throughput system. With this platform, we screened two compound libraries of 2,864 molecules and identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S-protein and the human cell ACE2 receptor. This data suggests that TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug. SIGNIFICANCE The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. In this present study, we screened two compound libraries of 2,864 molecules and identified a potent inhibitor (TS-984) for blocking the coronavirus S-protein and the human cell ACE2 receptor. TS-984 might have the potential to be developed into an effective anti-coronavirus drug for treating COVID-19.

Mathematical Analysis of the TB Model with Treatment via Caputo-Type Fractional Derivative

In this study, we formulate a noninteger-order mathematical model via the Caputo operator for the transmission dynamics of the bacterial disease tuberculosis (TB) in Khyber Pakhtunkhwa (KP), Pakistan. The number of confirmed cases from 2002 to 2017 is considered as incidence data for the estimation of parameters or to parameterize the model and analysis. The positivity and boundedness of the model solution are derived. For the dynamics of the tuberculosis model, we find the equilibrium points and the basic reproduction number. The proposed model is locally and globally stable at disease-free equilibrium, if the reproduction number ℛ0<1. Furthermore, to examine the behavior of the various parameters and different values of fractional-order derivative graphically, the most common iterative scheme based on fundamental theorem and Lagrange interpolation polynomial is implemented. From the numerical result, it is observed that the contact rate and treatment rate have a great impact on curtailing the tuberculosis disease. Furthermore, proper treatment is a key factor in reducing the TB transmission and prevalence. Also, the results are more precise for lower fractional order. The results from various numerical plots show that the fractional model gives more insights into the disease dynamics and on how to curtail the disease spread.