Adaptation of the infectious bronchitis virus H120 vaccine strain to Vero cell lines.

Infectious bronchitis virus (IBV) has restricted cell and tissue tropism. IBVs, except the Beaudette strain, can infect and replicate in chicken embryos, primary chicken embryo kidneys, and primary chicken kidney cells, only. The limited viral cell tropism of IBV substantially hinders in vitro cell-based research on pathogenic mechanisms and vaccine development. Herein, the parental H120 vaccine strain was serially passaged for five generations in chicken embryos, 20 passages in CK cells and 80 passages in Vero cells. This passaging yielded a Vero cell-adapted strain designated HV80. To further understand viral evolution, serial assessments of infection, replication, and transmission in Vero cells were performed for the viruses obtained every tenth passage. The ability to form syncytia and the replication efficiency significantly after the 50th passage (strain HV50). HV80 also displayed tropism extension to DF-1, BHK-21, HEK-293 T, and HeLa cells. Whole genome sequencing of viruses from every tenth generation revealed a total of 19 amino acid point mutations in the viral genome by passage 80, nine of which occurred in the S gene. The second furin cleavage site appeared in viral evolution and may be associated with cell tropism extension of HV80.

Acceptability and perception of COVID-19 vaccines among foreign medical students in China: A cross-sectional study.

Background: Acceptability and perception of the COVID-19 vaccine among different social groups have been the subject of several studies. However, little is known about foreign medical students in Chinese universities. Aim: This study, therefore, fills the literature gap using a focus group technique to assess the acceptance and perception of the COVID-19 vaccine among foreign medical students in China. Methods: The study adopted an online cross-sectional survey method following the Chinese universities' lockdowns to collect the data between March and April 2022. A data collection questionnaire was developed, and then the link was shared with the respondents through key informants in different universities in China to obtain the data. The data collection process only included foreign medical students who were in China from May 2021 to April 2022. The authors received a total of 403 responses from the respondents. During data processing, we excluded 17 respondents since they were not in China while administering the questionnaire to enhance the data validity. The authors then coded the remaining 386 respondents for the estimation process. We finally applied the multilinear logistics regression technique to model the COVID-19 vaccine acceptance with the response or influencing factors, including the mediating factors among the foreign medical students in China. Results: The data statistics show that 4.9% of the respondents were younger than 20 years, 91.5% were 20-40 years old, and 3.6% were older than 40 years; 36.3% of respondents were female subjects and 63.7% were male subjects. The results also show that the respondents are from six continents, including the African continent, 72.4%, Asia 17.4%, 3.1% from Europe, 2.8% from North America, 1.6% from Australia, and 2.3% from South America. The mediation analysis for the gender variable (ß = 0.235, p = 0.002) suggests that gender is a significant channel in COVID-19 vaccine acceptance and perception among foreign medical students in China. Also, the main analysis shows that opinion on the safety of the vaccine (ß = 0.081, p = 0.043), doses of the vaccine to receive (ß = 0.175, p = 0.001), vaccine safety with some side effects (ß = 0.15, p = 0.000), and the possibility of acquiring COVID-19 after vaccination (ß = 0.062, p = 0.040) are all positive factors influencing vaccine acceptability and perception. Also, the home continent (ß = -0.062, p = 0.071) is a negative factor influencing COVID-19 vaccine acceptance and perception. Furthermore, the finding shows that fear perceptions has affected 200 (51.81%) respondents. The medical students feared that the vaccines might result in future implications such as infertility, impotence, and systemic health conditions such as cardiovascular, respiratory, or deep vein thrombosis. In addition, 186 (48.19%) students feared that the vaccines were intended to shorten life expectancy. Conclusion: COVID-19 vaccination acceptability and perception among medical students in China is high, most predominantly due to their knowledge of medicine composition formulation. Despite widespread acceptance by the general public and private stakeholders, we concluded that vaccination resistance remains a significant factor among medical students and trainees. The study further adds that in considering the COVID-19 vaccine, the factor of the home continent plays a significant role in vaccine hesitancy among foreign medical students. Also, knowledge, information, and education are important pillars confronting new medicine administered among medical trainees. Finally, there is a low rate of COVID-19 vaccine hesitancy among foreign medical students in China. The study, therefore, recommends targeted policy strategies, including sensitization, detailed public information, and education, especially for medical colleges and institutions on the COVID-19 vaccination, to achieve 100%. Furthermore, the study recommends that future researchers explore other factors influencing accurate information and education for successful COVID-19 vaccination implementation.

Cross-species recognition and molecular basis of SARS-CoV-2 and SARS-CoV binding to ACE2s of marine animals.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has an extremely broad host range that includes hippopotami, which are phylogenetically closely related to whales. The cellular ACE2 receptor is one of the key determinants of the host range. Here, we found that ACE2s from several marine mammals and hippopotami could efficiently bind to the receptor-binding domain (RBD) of both SARS-CoV and SARS-CoV-2 and facilitate the transduction of SARS-CoV and SARS-CoV-2 pseudoviruses into ACE2-expressing cells. We further resolved the cryo-electron microscopy complex structures of the minke whale ACE2 and sea lion ACE2, respectively, bound to the RBDs, revealing that they have similar binding modes to human ACE2 when it comes to the SARS-CoV-2 RBD and SARS-CoV RBD. Our results indicate that marine mammals could potentially be new victims or virus carriers of SARS-CoV-2, which deserves further careful investigation and study. It will provide an early warning for the prospective monitoring of marine mammals.

Trends in operating room-based glaucoma procedures at a single eye center from 2016-2020.

AIM: To evaluate trends in glaucoma procedures at the Peking University Eye Center in 2016-2020. METHODS: A retrospective search of all glaucoma procedures performed at our institution were performed. Data were analyzed by calculating the absolute numbers and relative weightage of each procedure per year. RESULTS: The average age of glaucoma patients undergoing surgical procedures was 62.33±17.87y, and 55% were women. From 2016 to 2019, the number of surgical procedures performed in glaucoma patients showed an overall upward trend from 749 to 1460, although it decreased slightly in 2020 (n=1393), probably due to the COVID-19 pandemic. The number of trabeculectomies did not change significantly in 2016 (n=161) to 2018 (n=164) but decreased in 2019 (n=139) to 2020 (n=121), indicating a reduction in its relative weightage among glaucoma procedures (from 21.50% to 8.69%). The number of glaucoma drainage device implantations and minimally invasive glaucoma surgeries both increased (50 and 58 respectively in 2019), except in 2020. The number of transscleral cyclophotocoagulation procedures was relatively stable, increasing until 2017 (n=218) and then decreasing. Cataract surgeries with or without glaucoma procedures accounted for a large number of the total surgeries, increasing from 247 (32.97%) in 2016 to 967 (69.42%), among which cataract extraction combined with goniosynechialysis was the most frequent. CONCLUSION: The overall increase in the number of operating room-based surgical procedures is significant. Trabeculectomy is one of the most commonly performed procedures, despite the relative decline in its weightage. Other procedures, including use of glaucoma drainage devices and mini shunts and minimally invasive glaucoma surgeries, are gaining greater acceptance. Notably, lens-related surgery plays an important role in glaucoma management.

Characterization and pathogenicity of the porcine epidemic diarrhea virus isolated in China.

Piglet diarrhea caused by the porcine epidemic diarrhea virus (PEDV) is a common problem on pig farms in China associated with high morbidity and mortality rates. In this study, three PEDV isolates were successfully detected after the fourth blind passage in Vero cells. The samples were obtained from infected piglet farms in Jilin (Changchun), and Shandong (Qingdao) Provinces of China and were designated as CH/CC-1/2018, CH/CC-2/2018, and CH/QD/2018. According to the analysis of the complete S protein gene sequence, the CH/CC-1/2018 and CH/CC-2/2018 were allocated to the G2b branch, while CH/QD/2018 was located in the G1a interval and was closer to the vaccine strain CV777. Successful detection and identification of the isolated strains were carried out using electron microscopy and indirect immunofluorescence. Meanwhile, animal challenge experiments and viral RNA copies determination were used to compare the pathogenicity. The results showed that CH/CC-1/2018 in Changchun was more pathogenic than CH/QD/2018 in Qingdao. In conclusion, the discovery of these new strains is conducive to the development of vaccines to prevent the pandemic of PEDV, especially that the CH/CC-1/2018, and CH/CC-2/2018 were not related to the classical vaccine strain CV777.

Comparison of clinical characteristics between COVID-19 and H7N9 fatal cases: An observational study.

Objective: The outbreak of COVID-19 in 2020 is reminiscent of the H7N9 outbreak in 2013, which poses a huge threat to human health. We aim to compare clinical features and survival factors in fatal cases of COVID-19 and H7N9. Methods: Data on confirmed COVID-19 and H7N9 fatal cases identified in mainland China were analyzed to compare demographic characteristics and clinical severity. Survival curves were estimated by the Kaplan-Meier method and compared using log-rank tests and a restricted mean survival time model. A Cox regression model was used to identify survival factors in fatal cases of COVID-19 and H7N9. Results: Similar demographic characteristics were observed in fatal cases of COVID-19 and H7N9. The proportion of fatal cases of H7N9 receiving antibiotics, antiviral drugs, and oxygen treatment was higher than that of COVID-19. The potential protective factors for fatal COVID-19 cases were receiving antibiotics (HR: 0.37, 95% CI: 0.22-0.61), oxygen treatment (HR: 0.66, 95% CI: 0.44-0.99), and corticosteroids (HR: 0.46, 95% CI: 0.35-0.62). In contrast, antiviral drugs (HR: 0.21, 95% CI: 0.08-0.56) and corticosteroids (HR: 0.45, 95% CI: 0.29-0.69) were the protective factors for H7N9 fatal cases. Conclusion: The proportion of males, those having one or more underlying medical condition, and older age was high in COVID-19 and H7N9 fatal cases. Offering antibiotics, oxygen treatment, and corticosteroids to COVID-19 cases extended the survival time. Continued global surveillance remains an essential component of pandemic preparedness.

Inhibitory effects of ultralow-dose sodium hypochlorite on Microcystis aeruginosa and Chlorella vulgaris: Differences in sensitivity and physiology

Throughout the COVID-19 pandemic, the application of residual free chlorine has been emphasized as an effective disinfectant;however, the discharged residual chlorine is associated with potential ecological risk at concentrations even below 0.1 mg/L. However, the influence of free chlorine at ultralow-doses (far below 0.01 mg/L) on phytoplankton remains unclear. Due to limitations of detection limit and non-linear dissolution, different dilution rates (1/500, 1/1000, 1/5000, 1/10000, and 1/50000 DR) of a NaClO stock solution (1 mg/L) were adopted to represent ultralow-dose NaClO gradients. Two typical microalgae species, cyanobacterium Microcystis aeruginosa and chlorophyta Chlorella vulgaris, were explored under solo- and co-culture conditions to analyze the inhibitory effects of NaClO on microalgae growth and membrane damage. Additionally, the effects of ultralow-dose NaClO on photosynthesis activity, intracellular reactive oxygen species (ROS) production, and esterase activity were investigated, in order to explore physiological changes and sensitivity. With an initial microalgae cell density of approximately 1 × 106 cell/mL, an inhibitory effect on M. aeruginosa was achieved at a NaClO dosage above 1/10000 DR, which was lower than that of C. vulgaris (above 1/5000 DR). The variation in membrane integrity and photosynthetic activity further demonstrated that the sensitivity of M. aeruginosa to NaClO was higher than that of C. vulgaris, both in solo- and co-culture conditions. Moreover, NaClO is able to interfere with photosynthetic activity, ROS levels, and esterase activity. Photosynthetic activity declined gradually in both microalgae species under sensitive NaClO dosage, but esterase activity increased more rapidly in M. aeruginosa, similar to the behavior of ROS in C. vulgaris. These findings of differing NaClO sensitivity and variations in physiological activity between the two microalgae species contribute to a clearer understanding of the potential ecological risk associated with ultralow-dose chlorine, and provide a basis for practical considerations. Graphical Unlabelled Image

Comparison of clinical characteristics between COVID-19 and H7N9 fatal cases: An observational study

Objective The outbreak of COVID-19 in 2020 is reminiscent of the H7N9 outbreak in 2013, which poses a huge threat to human health. We aim to compare clinical features and survival factors in fatal cases of COVID-19 and H7N9. Methods Data on confirmed COVID-19 and H7N9 fatal cases identified in mainland China were analyzed to compare demographic characteristics and clinical severity. Survival curves were estimated by the Kaplan–Meier method and compared using log-rank tests and a restricted mean survival time model. A Cox regression model was used to identify survival factors in fatal cases of COVID-19 and H7N9. Results Similar demographic characteristics were observed in fatal cases of COVID-19 and H7N9. The proportion of fatal cases of H7N9 receiving antibiotics, antiviral drugs, and oxygen treatment was higher than that of COVID-19. The potential protective factors for fatal COVID-19 cases were receiving antibiotics (HR: 0.37, 95% CI: 0.22–0.61), oxygen treatment (HR: 0.66, 95% CI: 0.44–0.99), and corticosteroids (HR: 0.46, 95% CI: 0.35–0.62). In contrast, antiviral drugs (HR: 0.21, 95% CI: 0.08–0.56) and corticosteroids (HR: 0.45, 95% CI: 0.29–0.69) were the protective factors for H7N9 fatal cases. Conclusion The proportion of males, those having one or more underlying medical condition, and older age was high in COVID-19 and H7N9 fatal cases. Offering antibiotics, oxygen treatment, and corticosteroids to COVID-19 cases extended the survival time. Continued global surveillance remains an essential component of pandemic preparedness.

Structural basis of SARS-CoV-2 and its variants binding to intermediate horseshoe bat ACE2.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic. Intermediate horseshoe bats (Rhinolophus affinis) are hosts of RaTG13, the second most phylogenetically related viruses to SARS-CoV-2. We report the binding between intermediate horseshoe bat ACE2 (bACE2-Ra) and SARS-CoV-2 receptor-binding domain (RBD), supporting the pseudotyped SARS-CoV-2 viral infection. A 3.3 Å resolution crystal structure of the bACE2-Ra/SARS-CoV-2 RBD complex was determined. The interaction networks of Patch 1 showed differences in R34 and E35 of bACE2-Ra compared to hACE2 and big-eared horseshoe bat ACE2 (bACE2-Rm). The E35K substitution, existing in other species, significantly enhanced the binding affinity owing to its electrostatic attraction with E484 of SARS-CoV-2 RBD. Furthermore, bACE2-Ra showed extensive support for the SARS-CoV-2 variants. These results broaden our knowledge of the ACE2/RBD interaction mechanism and emphasize the importance of continued surveillance of intermediate horseshoe bats to prevent spillover risk.

Rapid and Visual RPA-Cas12a Fluorescence Assay for Accurate Detection of Dermatophytes in Cats and Dogs.

Dermatophytosis, an infectious disease caused by several fungi, can affect the hair, nails, and/or superficial layers of the skin and is of global significance. The most common dermatophytes in cats and dogs are Microsporum canis and Trichophyton mentagrophytes. Wood's lamp examination, microscopic identification, and fungal culture are the conventional clinical diagnostic methods, while PCR (Polymerase Chain Reaction) and qPCR (Quantitative PCR) are playing an increasingly important role in the identification of dermatophytes. However, none of these methods could be applied to point-of-care testing (POCT). The recent development of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) based diagnostic platform promises a rapid, accurate, and portable diagnostic tool. In this paper, we present a Cas12a-fluorescence assay to detect and differentiate the main dermatophytes in clinical samples with high specificity and sensitivity. The Cas12a-based assay was performed with a combination of recombinase polymerase amplification (RPA). The results could be directly visualized by naked eyes under blue light, and all tested samples were consistent with fungal culture and sequencing results. Compared with traditional methods, the RPA-Cas12a-fluorescence assay requires less time (about 30 min) and less complicated equipment, and the visual changes can be clearly observed with naked eyes, which is suitable for on-site clinical diagnosis.

A new circular RNA-encoded protein BIRC6-236aa inhibits transmissible gastroenteritis virus (TGEV)-induced mitochondrial dysfunction.

Transmissible gastroenteritis virus (TGEV), a member of the coronavirus family, is the pathogen responsible for transmissible gastroenteritis, which results in mitochondrial dysfunction in host cells. Previously, we identified 123 differentially expressed circular RNAs (cRNA)from the TGEV-infected porcine intestinal epithelial cell line jejunum 2 (IPEC-J2). Previous bioinformatics analysis suggested that, of these, circBIRC6 had the potential to regulate mitochondrial function. Furthermore, mitochondrial permeability transition, a key step in the process of mitochondrial dysfunction, is known to be caused by abnormal opening of mitochondrial permeability transition pores (mPTPs) regulated by the voltage-dependent anion-selective channel protein 1 (VDAC)-Cyclophilin D (CypD) complex. Therefore, in the present study, we investigated the effects of circBIRC6-2 on mitochondrial dysfunction and opening of mPTPs. We found that TGEV infection reduced circBIRC6-2 levels, which in turn reduced mitochondrial calcium (Ca2+) levels, the decrease of mitochondrial membrane potential, and opening of mPTPs. In addition, we also identified ORFs and internal ribosomal entrance sites within the circBIRC6-2 RNA. We demonstrate circBIRC6-2 encodes a novel protein, BIRC6-236aa, which we show inhibits TGEV-induced opening of mPTPs during TGEV infection. Mechanistically, we identified an interaction between BIRC6-236aa and VDAC1, suggesting that BIRC6-236aa destabilizes the VDAC1-CypD complex. Taken together, the results suggest that the novel protein BIRC6-236aa encoded by cRNA circBIRC6-2 inhibits mPTP opening and subsequent mitochondrial dysfunction by interacting with VDAC1.

Broader-species receptor binding and structural bases of Omicron SARS-CoV-2 to both mouse and palm-civet ACE2s.

The Omicron variant of SARS-CoV-2 carries multiple unusual mutations, particularly in the receptor-binding domain (RBD) of the spike (S) protein. Moreover, host-adapting mutations, such as residues 493, 498, and 501, were also observed in the Omicron RBD, which indicates that it is necessary to evaluate the interspecies transmission risk of the Omicron variant. Herein, we evaluated the interspecies recognition of the Omicron BA.1 and Delta RBDs by 27 ACE2 orthologs, including humans. We found that Omicron BA.1 expanded its receptor binding spectra to palm-civet, rodents, more bats (least horseshoe bat and greater horseshoe bat) and lesser hedgehog tenrec. Additionally, we determined the cryo-electron microscopy (cryo-EM) structure of the Omicron BA.1 S protein complexed with mouse ACE2 (mACE2) and the crystal structure of Omicron RBD complexed with palm-civet ACE2 (cvACE2). Several key residues for the host range have been identified. These results suggest that surveillance should be enhanced on the Omicron variant for its broader-species receptor binding to prevent spillover and expansion of reservoir hosts for a prolonged pandemic.

Problematic Internet use and academic engagement during the COVID-19 lockdown: The indirect effects of depression, anxiety, and insomnia in early, middle, and late adolescence.

BACKGROUND: During the COVID-19 pandemic, the transition of online learning introduces challenges for adolescents to engage in learning. The increased access and persistent Internet use could heighten the risk of problematic Internet use (PIU) that has been increasingly recognized as a risk factor for academic engagement. This study aims to investigate the direct and indirect relationships between PIU and academic engagement through psychopathological symptoms (i.e., depression, anxiety, insomnia) in early, middle, and late adolescence. METHODS: In all, 4852 adolescents (51.5% females; Mage = 13.80 ± 2.38) from different regions of Chinese mainland participated in the study and completed questionnaires. RESULTS: Depression and then insomnia as well as anxiety and then insomnia mediated the relationship between PIU and academic engagement. Anxiety exhibited a double-edged effect, that is, a positive relation with academic engagement directly and a negative relation with academic engagement indirectly through insomnia. Multigroup analyses showed that the indirect effects of PIU on academic engagement through depression and subsequent insomnia in middle and late adolescence were stronger than that in early adolescence, whereas the direct effect in early adolescence was stronger than that in middle adolescence. LIMITATION: This study was cross-sectional in design and relied upon self-report measures. CONCLUSION: These findings improve the understandings of how PIU relates to academic engagement through psychopathological symptoms and highlight developmental differences of adolescence.

Predicting Psychological State Among Chinese Undergraduate Students in the COVID-19 Epidemic: A Longitudinal Study Using a Machine Learning.

BACKGROUND: The outbreak of the 2019 novel coronavirus disease (COVID-19) not only caused physical abnormalities, but also caused psychological distress, especially for undergraduate students who are facing the pressure of academic study and work. We aimed to explore the prevalence rate of probable anxiety and probable insomnia and to find the risk factors among a longitudinal study of undergraduate students using the approach of machine learning. METHODS: The baseline data (T1) were collected from freshmen who underwent psychological evaluation at two months after entering the university. At T2 stage (February 10th to 13th, 2020), we used a convenience cluster sampling to assess psychological state (probable anxiety was assessed by general anxiety disorder-7 and probable insomnia was assessed by insomnia severity index-7) based on a web survey. We integrated information attained at T1 stage to predict probable anxiety and probable insomnia at T2 stage using a machine learning algorithm (XGBoost). RESULTS: Finally, we included 2009 students (response rate: 80.36%). The prevalence rate of probable anxiety and probable insomnia was 12.49% and 16.87%, respectively. The XGBoost algorithm predicted 1954 out of 2009 students (translated into 97.3% accuracy) and 1932 out of 2009 students (translated into 96.2% accuracy) who suffered anxiety and insomnia symptoms, respectively. The most relevant variables in predicting probable anxiety included romantic relationship, suicidal ideation, sleep symptoms, and a history of anxiety symptoms. The most relevant variables in predicting probable insomnia included aggression, psychotic experiences, suicidal ideation, and romantic relationship. CONCLUSION: Risks for probable anxiety and probable insomnia among undergraduate students can be identified at an individual level by baseline data. Thus, timely psychological intervention for anxiety and insomnia symptoms among undergraduate students is needed considering the above factors.

The Impact of Consumer Purchase Behavior Changes on the Business Model Design of Consumer Services Companies Over the Course of COVID-19.

The COVID-19 pandemic has had a profound psychological and behavioral impact on people around the world. Consumer purchase behaviors have thus changed greatly, and consumer services companies need to adjust their business models to adapt to this change. From the perspective of consumer psychology, this paper explores the impact of consumer purchase behavior changes over the course of the pandemic on the business model design of consumer services companies using a representative survey of 1,742 individuals. Our results show that changes in consumer purchase behavior have a significant impact on the design of consumer services firms' business models. Specifically, changes in consumers' purchase object, motive, and timeframe are more likely to spark a novelty-centered business model design, whereas changes in purchase method tend to inspire an efficiency-centered one. Our findings provide a theoretical reference for consumer services companies in designing business models when faced with unexpected crises.

Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic continues worldwide with many variants arising, some of which are variants of concern (VOCs). A recent VOC, omicron (B.1.1.529), which obtains a large number of mutations in the receptor-binding domain (RBD) of the spike protein, has risen to intense scientific and public attention. Here, we studied the binding properties between the human receptor ACE2 (hACE2) and the VOC RBDs and resolved the crystal and cryoelectron microscopy structures of the omicron RBD-hACE2 complex as well as the crystal structure of the delta RBD-hACE2 complex. We found that, unlike alpha, beta, and gamma, omicron RBD binds to hACE2 at a similar affinity to that of the prototype RBD, which might be due to compensation of multiple mutations for both immune escape and transmissibility. The complex structures of omicron RBD-hACE2 and delta RBD-hACE2 reveal the structural basis of how RBD-specific mutations bind to hACE2.

Effect of the App-Based Video Guidance on Prenatal Pelvic Floor Muscle Training Combined with Global Postural Re-education for Stress Urinary Incontinence Prevention: A Protocol for a Multicenter, Randomized Controlled Trial.

BACKGROUND: As the effectiveness on stress urinary incontinence (SUI) prevention of pelvic floor muscle training (PFMT) for pregnant women has been inconclusive, we are planning to conduct a trial to evaluate a video program designed for prevention of SUI developed through combining PFMT with global postural reeducation (GPR). METHODS: As a randomized controlled trial, eligible participants will be randomized (1:1) into an exercise group and a control group to perform PFMT regularly following video guidance or with no intervention, respectively. The experimental stage will be from the 16th gestation week (GW) to the 12th month postpartum, with eight appointments at the 16th, 28th, 37th GW, delivery, the 6th week and the 3rd, 6th, and 12th month postpartum. Data will be collected regarding urinary leakage symptoms, the stress test, the modified Oxford Scale, pelvic floor ultrasound, perineal laceration classification at delivery, neonatal Apgar score, and questionnaires (PISQ-12, ICIQ-UI SF, I-QOL, OABSS). The primary outcome is the occurrence of the symptomatic SUI and positive stress test at the 6th week postpartum. DISCUSSION: This protocol is anticipated to evaluate the efficacy of the intervention via video app for the design of a future randomized control trial (RCT). TRIAL REGISTRATION: The trial has been registered at Chinese Clinical Trial Registry (registration number: ChiCTR2000029618).

Hydrophobic Optimization of Functional Poly(TPAE-co-suberoyl chloride) for Extrahepatic mRNA Delivery following Intravenous Administration.

Messenger RNA (mRNA) has generated great attention due to its broad potential therapeutic applications, including vaccines, protein replacement therapy, and immunotherapy. Compared to other nucleic acids (e.g., siRNA and pDNA), there are more opportunities to improve the delivery efficacy of mRNA through systematic optimization. In this report, we studied a high-throughput library of 1200 functional polyesters for systemic mRNA delivery. We focused on the chemical investigation of hydrophobic optimization as a method to adjust mRNA polyplex stability, diameter, pKa, and efficacy. Focusing on a region of the library heatmap (PE4K-A17), we further explored the delivery of luciferase mRNA to IGROV1 ovarian cancer cells in vitro and to C57BL/6 mice in vivo following intravenous administration. PE4K-A17-0.2C8 was identified as an efficacious carrier for delivering mRNA to mouse lungs. The delivery selectivity between organs (lungs versus spleen) was found to be tunable through chemical modification of polyesters (both alkyl chain length and molar ratio in the formulation). Cre recombinase mRNA was delivered to the Lox-stop-lox tdTomato mouse model to study potential application in gene editing. Overall, we identified a series of polymer-mRNA polyplexes stabilized with Pluronic F-127 for safe and effective delivery to mouse lungs and spleens. Structure-activity relationships between alkyl side chains and in vivo delivery were elucidated, which may be informative for the continued development of polymer-based mRNA delivery.

Disinformation of text mining online about tobacco and the COVID-19 discussed on Sina Weibo.

INTRODUCTION: During the COVID-19 pandemic, various types of disinformation have emerged from the media. This study focuses on the online disinformation about tobacco and the COVID-19 on the Sina Weibo, the Chinese largest new media microblog platform. METHODS: The related posts from the beginning of the epidemic in December 2019 to 19 January 2021 were searched. Text mining technology was applied on these posts to identify content on 'smoking can prevent COVID-19'. Descriptive research was used to analyze the dataset. RESULTS: Among the 912 original posts, 508 informative posts were selected after artificial recognition, including 112 posts of spreading disinformation and 396 which dispel the disinformation. Of the disinformation posts, 74% (83/112) cited the results of scientific research, and 17% (19/112) mentioned that smog from burning Asian wormwood could prevent COVID-19. By analyzing the public's comments on these 112 disinformation posts, it was suggested that about 12% of the comments were in support, and 88% of the posts were opposed or invalid. The proportion of supportive comments on pseudo-scientific information was higher than on plain disinformation, 21% and 9%, respectively. CONCLUSIONS: The disinformation of promoting smoking as a way to prevent COVID-19 has the typical feature of using pseudo-scientific arguments to package disinformation, making it very difficult for readers without professional knowledge to identify. Such actions harm both tobacco control and COVID-19 prevention.

Risk of Covid-19-Related Hospitalization and More Severe Outcomes in Medicare Beneficiaries Treated with Renin-Angiotensin-Aldosterone System Inhibitors for Hypertension.

BACKGROUND: There are theoretical concerns that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could increase the risk of severe Covid-19. OBJECTIVE: To determine if ACEIs and ARBs are associated with an increased risk of Covid-19 hospitalization overall, or hospitalization involving intensive care unit (ICU) admission, invasive mechanical ventilation, or death. DESIGN: Observational case-control study. PARTICIPANTS: Medicare beneficiaries aged ≥ 66 years with hypertension, treated with ACEIs, ARBs, calcium channel blockers (CCBs), or thiazide diuretics. MAIN MEASURES: Adjusted odds ratios (OR) and 95% confidence intervals (CI) for the outcomes of Covid-19 hospitalization, or hospitalization involving ICU admission, invasive mechanical ventilation, or death. RESULTS: A total of 35,300 cases of hospitalized Covid-19 were matched to 228,228 controls on calendar date and neighborhood of residence. The median age of cases was 79 years, 57.4% were female, and the median duration of hospitalization was 8 days (interquartile range 5-12). ACEIs and ARBs were associated with a slight reduction in Covid-19 hospitalization risk compared with treatment with other first-line antihypertensives (OR for ACEIs 0.95, 95% CI 0.92-0.98; OR for ARBs 0.94, 95% CI 0.90-0.97). Similar results were obtained for hospitalizations involving ICU admission, invasive mechanical ventilation, or death. There were no meaningful differences in risk for ACEIs compared with ARBs. In an analysis restricted to monotherapy with a first-line agent, CCBs were associated with a small increased risk of Covid-19 hospitalization compared with ACEIs (OR 1.09, 95% CI 1.04-1.14), ARBs (OR 1.10, 95% CI 1.05-1.15), or thiazide diuretics (OR 1.11, 95% CI 1.03-1.19). CONCLUSIONS: ACEIs and ARBs were not associated with an increased risk of Covid-19 hospitalization or with hospitalization involving ICU admission, invasive mechanical ventilation, or death. The finding of a small increased risk of Covid-19 hospitalization with CCBs was unexpected and could be due to residual confounding.