Research on patient-centered design for post-stroke depression patients based on SEM and comprehensive evaluation.

Introduction: Since COVID-19, medical resources have been tight, making it inconvenient to go offline for the sequelae of diseases such as post-stroke depression (PSD) that require long-term follow-up. As a new digital therapy, VRTL began to gain popularity. Method: The research is divided into two parts: pre-test and post-test. In the pre-test, an evaluation method integrating reality-based interaction (RBI), structural equation model (SEM), analytic hierarchy process (AHP), and entropy weight method is proposed. In the post-test the patients' physiological indicators (Diastolic blood pressure, systolic blood pressure and heart rate) are measured to verify the effectiveness of RBI-SEM model using T-test method. Results: In the pre-test, using SEM, it was confirmed that Pi physical awareness, Bi body awareness, Ei environmental awareness, and Si social awareness were significantly correlated and positively affected VRTL satisfaction (p >> F 0.217; B >> F 0.130; E >> F 0.243; S >> F 0.122). The comprehensive weight ranking based on RBI-SEM considered light environment (0.665), vegetation diversity (0.667), accessible roaming space (0.550) et al. relatively of importance. And T-tset in the post-test experiment considered that the data of the two measurements before and after the VRTL experience, systolic blood pressure (p < 0.01), diastolic blood pressure (p < 0.01), and blood pressure (p < 0.01) were significantly decreased; one-way ANOVA concluded that there was no significant difference in the changes of blood pressure and heart rate among participants of different ages and genders (p > 0.01). Conclusion: This research validated the effectiveness of RBI theory for VRTL design guidelines, established an RBI-SEM based VRTL evaluation model, and the output VRTL for PSD in the older adults was confirmed to have significant therapeutic benefits. This lays the foundation for designers to decompose design tasks and integrate VRTL into traditional clinical treatment systems. Contribution from the public or patients: Four public health department employees helped to improve the research's content.

Assessing the impact of architectural and behavioral interventions for controlling indoor COVID-19 infection risk: An agent-based approach

The COVID-19 pandemic changed our lives, forcing us to reconsider our built environment. In some buildings with high traffic flow, infected individuals release viral particles during movement. The complex interactions between humans, building, and viruses make it difficult to predict indoor infection risk by traditional computational fluid dynamics methods. The paper developed a spatially-explicit agent-based model to simulate indoor respiratory pathogen transmission for buildings with frequent movement of people. The social force model simulating pedestrian movement and a simple forcing method simulating indoor airflow were coupled in an agent-based modeling environment. The impact of architectural and behavioral interventions on the indoor infection risk was then compared by simulating a supermarket case. We found that wearing a mask was the most effective single intervention, with all people wearing masks reducing the percentage of infections to 0.08%. Among the combined interventions, the combination of customer control is the most effective and can reduce the percentage of infections to 0.04%. In addition, the extremely strict combination of all the interventions makes the supermarket free of new infections during its 8-hour operation. The approach can help architects, managers, or the government better understand the effect of nonpharmaceutical interventions to reduce the infection risk and improve the level of indoor safety.

Cardiac complications in children with acute COVID-19 vs multisystem inflammatory syndrome in children (MIS-C).

BACKGROUND: Cardiac involvement can lead to significant morbidity in children with acute COVID-19 or multisystem inflammatory syndrome in children (MIS-C). However, the presentation and outcomes of cardiac involvement may differ among these 2 conditions. We aimed to compare the frequency and extent of cardiac involvement among children admitted with acute COVID-19 vs those with MIS-C. METHODS: We conducted a cross sectional study of patients admitted to our hospital from March 2020 to August 2021 with symptomatic acute COVID-19 or MIS-C. Cardiac involvement was defined by presence of 1 or more of the following: elevated troponin, elevated brain natriuretic peptide, reduced left ventricular ejection fraction on echocardiogram, coronary dilation on echocardiogram, or abnormal electrocardiogram reading. RESULTS: Among 346 acute COVID-19 patients with median age of 8.9 years and 304 MIS-C patients with median age of 9.1 years, cardiac involvement was present in 33 acute COVID-19 patients (9.5%) and 253 MIS-C patients (83.2%). The most common cardiac abnormality was abnormal electrocardiogram in acute COVID-19 patients (7.5%) and elevated troponin in MIS-C patients (67.8%). Among acute COVID-19 patients, obesity was significantly associated with cardiac involvement. Among MIS-C patients, non-Hispanic Black race/ethnicity was significantly associated with cardiac involvement. CONCLUSIONS: Cardiac involvement is much more common in children with MIS-C than in those with acute COVID-19. These results reinforce our standardized practice of performing full cardiac evaluations and follow-up in all patients with MIS-C but only in acute COVID-19 patients with signs or symptoms of cardiac involvement.

Biodegradable Microrobots for DNA Vaccine Delivery.

The delivery of nucleic acid vaccine to stimulate host immune responses against Coronavirus disease 2019 shows promise. However, nucleic acid vaccines have drawbacks, including rapid clearance and poor cellular uptake, that limit their therapeutic potential. Microrobots can be engineered to sustain vaccine release and further control the interactions with immune cells that are vital for robust vaccination. Here, the 3D fabrication of biocompatible and biodegradable microrobots via the two-photon polymerization of gelatin methacryloyl (GelMA) and their proof-of-concept application for DNA vaccine delivery is reported. Programmed degradation and drug release by varying the local exposure dose in 3D laser lithography and further functionalized the GelMA microspheres with polyethyleneimine for DNA vaccine delivery to dendritic cell and primary cells is demonstrated. In mice, the DNA vaccine delivered by functionalized microspheres elicited fast, enhanced, and durable antigen expression, which may lead to prolonged protection. Furthermore, we demonstrated the maneuverability of microrobots by fabricating GelMA microspheres on magnetic skeletons. In conclusion, GelMA microrobots may provide an efficient vaccination strategy by controlling the expression duration of DNA vaccines.

Heparan sulfate promotes ACE2 super-cluster assembly to enhance SARS-CoV-2-associated syncytium formation.

The mechanism of syncytium formation, caused by spike-induced cell-cell fusion in severe COVID-19, is largely unclear. Here we combine chemical genetics with 4D confocal imaging to establish the cell surface heparan sulfate (HS) as a critical host factor exploited by SARS-CoV-2 to enhance spike’s fusogenic activity. HS binds spike to facilitate ACE2 clustering, generating synapse-like cell-cell contacts to promote fusion pore formation. ACE2 clustering, and thus, syncytium formation is significantly mitigated by chemical or genetic elimination of cell surface HS, while in a cell-free system consisting of purified HS, spike, and lipid-anchored ACE2, HS directly induces ACE2 clustering. Importantly, the interaction of HS with spike allosterically enables a conserved ACE2 linker in receptor clustering, which concentrates spike at the fusion site to overcome fusion-associated activity loss. This fusion-boosting mechanism can be effectively targeted by an investigational HS-binding drug, which reduces syncytium formation in vitro and viral infection in mice.

Repurposing niclosamide as a novel anti-SARS-Cov-2 drug by restricting entry protein CD147.

Background The burst of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the global COVID-19 pandemic. But until today only limited numbers of drugs are discovered to treat COVID-19 patients. Even worse, the rapid mutations of SARS-CoV-2 compromise the effectiveness of existing vaccines and neutralizing antibodies due to the increased viral transmissibility and immune escape. CD147-spike protein, one of the entries of SRAR-CoV-2 into host cells, has been reported as a promising therapeutic target for developing drugs against COVID-19. Methods CRISPR-Cas9 induced gene knockout, western blotting, tet-off protein overexpression, ribonucleoprotein IP and RNA-IP were used to confirm the regulation of HuR on mRNA of CD147. Regulation of niclosamide on HuR nucleo-translocation was assessed by immunofluorescence staining of cell lines, IHC staining of tissue of mouse model and western blotting. Finally, the suppression of niclosamide on SARS-CoV-2 infection induced CD147 was evaluated by ACE2-expressing A549 cells and western blotting. Results We first discovered a novel regulation mechanism of CD147 via the RNA-binding protein HuR. We found that HuR regulates CD147 post-transcription by directly bound to its 3'-UTR. The loss of HuR reduced CD147 in multiple cell lines. Niclosamide inhibited CD147 function by blocking HuR cytoplasmic translocation and diminishing CD147 glycosylation. SARS-CoV-2 infection induced CD147 in ACE2-expressing A549 cells, which could be neutralized by niclosamide in a dose-dependent manner. Conclusion Together, our study reveals a novel regulation mechanism of CD147 and niclosamide can be repurposed as an effective COVID-19 drug by targeting the virus entry, CD147-spike protein.

Effectiveness of telehealth-based exercise interventions on pain, physical function and quality of life in patients with knee osteoarthritis: A meta-analysis.

OBJECTIVE: The objective of the study was to evaluate the effectiveness of telehealth-based exercise intervention on pain, physical function and quality of life in patients with knee osteoarthritis. DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs). METHODS: Six databases (PubMed, Embase, Cochrane Library, CINAHL, PEDro and Web of Science Core Collection) were searched for relevant randomised controlled trials published from database inception to 3 June 2021. Reviewers independently screened the literature, extracted data and used the Cochrane Collaboration Risk of Bias Tool for quality assessment. A meta-analysis and subgroup analyses, stratified by control condition, intervention duration and delivery type, were conducted by Revman 5.4. The study was reported in compliance with PRISMA statement. RESULTS: A total of 9 independent RCTs with 861 participants were included. The meta-analysis showed that the telehealth-based exercise interventions significantly reduced pain in KOA patients (SMD = -0.28, 95% CI [-0.49, -0.08], p < .01) and produced similar effects to controls in terms of physical function and quality of life. Subgroup analysis revealed that telehealth-based exercise interventions were superior to the use of exercise booklet and usual care in terms of pain and physical function and were similar to face-to-face exercise treatment; a long-term (>3 months) intervention and the use of web and smartphone APPs to deliver exercise interventions were associated with better pain relief and physical function. CONCLUSIONS: Telehealth-based exercise intervention is an effective strategy for KOA management during the COVID-19 epidemic, and it is significantly better than usual care in reducing knee pain and improving physical function and was able to achieve the effects of traditional face-to-face exercise treatment. Although the duration and type of delivery associated with the effect of the intervention have been identified, patient preference and acceptability need to be considered in practice.

A universal CRISPR/Cas12a-powered intelligent point-of-care testing platform for multiple small molecules in the healthcare, environment, and food.

Growing studies focusing on nuclear acid detection via the emerging CRISPR technique demonstrate its promising application. However, limited works solve the identification of non-nucleic acid targets, especially multiple small molecules. To address challenges for point-of-care testing (POCT) in complex matrices for healthcare, environment, and food safety, we developed CRISPR Cas12a-powered highly sensitive, high throughput, intelligent POCT (iPOCT) for multiple small molecules based on a smartphone-controlled reader. As a proof of concept, aflatoxin B1 (AFB1), benzo[a]pyrene (BaP), and capsaicin (CAP) were chosen as multiple targets. First, three antigens were preloaded in independent microwells. Then, the antibody/antigen-induced fluorescent signals were consecutively transferred from the biotin-streptavidin to CRISPR/Cas12a system. Third, the fluorescent signals were recorded by a smartphone-controlled handheld dark-box readout. Under optimization, detection limits in AFB1, BaP, and CAP were 0.00257, 4.971, and 794.6 fg/mL with wide linear ranges up to four orders of magnitude. Using urine, water, soybean oil, wheat, and peanuts as the complex matrix, we recorded high selectivity, considerable recovery, repeatability, and high consistency comparison to HPLC-MS/MS methods. This work promises a practical intelligent POCT platform for multiple targets in lipid-soluble and water-soluble matrices and could be extensively applied for healthcare, environment, and food safety.

The Influence of Academic Self-Efficacy on University Students' Academic Performance: The Mediating Effect of Academic Engagement

Challenges and competition are being faced in higher education. Students' unsatisfactory academic performance and dropouts are obvious problems worldwide. The "student-centered” pedagogy requires universities to pay attention to the needs of students. Research has demonstrated that academic self-efficacy is a positive psychological variable in the prevention of students becoming academically burnt out and withdrawing from their studies. By increasing academic engagement and improving academic performance, academic self-efficacy can reduce the dropout rates. This study attempted to achieve an in-depth comprehension of the nexus between academic self-efficacy and academic achievement among university students and the mediating role of academic engagement in the association between the two. A total of 258 participants were included in the cross-sectional study. The relationships among academic self-efficacy, academic engagement, and academic performance were examined using Pearson correlation coefficients. In order to examine the intermediating role of academic engagement in the relationship between academic self-efficacy and academic performance, a mediation analysis was applied. A favorable and strong correlation among academic self-efficacy, academic engagement, and academic performance was found in this study. Academic self-efficacy can be a direct predictor of academic achievement and can also be an indirect predictor of academic achievement via the intermediating effect of academic engagement. The findings of this study provide theoretical and practical recommendations for university researchers and administrators. The findings confirm the mediating role of academic engagement between academic self-efficacy and academic performance. The results provide universities with evidence for use in the design of projects and programs for the improvement of students' academic performance. Increasing the level of academic self-efficacy and enhancing academic engagement are of utmost importance for university students to maintain and improve their academic performance.

A propensity score matching study: The prevalence of mental health problems among pregnant women at first antenatal care increased in Chongqing during the first wave of the COVID-19 pandemic

Background The 2019 coronavirus disease (COVID-19) pandemic increased the risks of mental health challenges, especially anxiety and depression. However, the impact of COVID-19 on mental health during pregnancy has not been fully established. Therefore, we investigated the impact of the COVID-19 pandemic on maternal mental health. Methods Two cohorts of pregnant women at their first antenatal care in the First Affiliated Hospital of Chongqing Medical University were enrolled in this study. One cohort was enrolled before the COVID-19 outbreak, from 1 June to 31 December 2019 (n = 5,728, pre-COVID-19 group), while the other was enrolled during the COVID-19 pandemic, from 24 January to 23 March 2020 (n = 739, COVID-19 pandemic group). Symptoms of depression, anxiety, and somatization disorders were assessed by the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-15 (PHQ-15), with a cutoff point of 10 for moderate-to-severe depression, anxiety, and somatoform symptoms. The propensity score matching method (1:1) was used to balance differences in demographic characteristics between groups. A chi-square analysis was performed to compare differences in demographic characteristics between the groups. Results Prevalence of moderate-to-severe depression, anxiety, and somatoform symptoms among pregnant women at their first antenatal care visit during the COVID-19 pandemic (9.5, 2.2, and 20.8%, respectively) was significantly lower than those before the pandemic (16.3, 4.4, and 25.7%, respectively) (p < 0.05). Compared with the same period before the pandemic, during the pandemic, the number of women newly registered for antenatal care decreased by nearly 50%. There were significant differences in the distributions of demographic characteristics between the groups (p < 0.05). After matching the demographic characteristics, differences in the prevalence of maternal mental health disorders between the groups reversed dramatically. Prevalence of moderate-to-severe depression, anxiety, and somatoform symptoms during the COVID-19 pandemic in this population (2.3, 9.6, and 20.8%, respectively) was significantly higher than those before the pandemic (0.3, 3.9, and 10%, respectively) (p < 0.05). Conclusion The COVID-19 pandemic increased mental health risks among pregnant women. As a large proportion of pregnant women with mental health challenges delay their prenatal care or change healthcare facilities after the outbreak of public health emergencies, there is a need to establish a balanced healthcare system in medical institutions at all levels.

Dendrobium officinale aqueous extract influences the immune response following vaccination against SARS-CoV-2.

BACKGROUND: Vaccination is the most effective way to prevent coronavirus disease 2019 (COVID-19). However, it is often less protective and does not significantly increase antibody levels, especially in individuals with impaired immune systems. Nevertheless, the immunocompetence can be enhanced using a natural immunomodulator, such as Dendrobium officinale aqueous extract (DoAE). METHODS: To determine whether DoAE promotes antibody production, we treated healthy volunteers with DoAE during COVID-19 vaccination. Meanwhile, the control volunteers were given a placebo (cornstarch) during the vaccination. Antibody levels were measured at three-week intervals in the DoAE and control groups. RESULTS: DoAE enhanced immunity and preserved immune cell homeostasis. However, the neutralizing antibody (nAb) levels in the DoAE group were lower than those in the control group. Analysis of the gut microbiota revealed that the abundance of anti-inflammatory flora was increased, while the pro-inflammatory flora was reduced in the DoAE group. CONCLUSION: DoAE has immunomodulatory and anti-inflammatory properties. Therefore, DoAE has the potential for COVID-19 prophylaxis, treatment, and recovery from the adverse effects of COVID-19. However, its anti-inflammatory activity affects the production of nAbs. Thus, DoAE may not be recommended for consumption during COVID-19 vaccination.

The construction of patient quality management model in oral post anesthesia care unit in China: a grounded theory approach.

BACKGROUND: Nowadays, people have paid more and more attention to the quality of physical and mental health recovery after oral surgery anesthesia. As a remarkable feature of patient quality management, it can effectively reduce the risk of postoperative complications and pain in Post Anesthesia Care Unit (PACU). However, the patient management model in oral PACU remains unknown, especially in China. The purpose of this study is to explore the management elements of patient quality management in the oral PACU and to construct the management model. METHODS: Strauss and Corbin's grounded theory method was used to explore the experiences of three anesthesiologists, six anesthesia nurses and three administrators working in oral PACU. Twelve semi-structured interviews were conducted using face-to-face in a tertiary stomatological hospital from March to June, 2022. The interviews were transcribed and thematically analysed according to QSR NVivo 12.0 qualitative analysis tool. RESULTS: Three themes and ten subthemes were identified through an active analysis process, including three of the core team members: stomatological anesthesiologists, stomatological anesthesia nurses and administrators, three of the main functions: education and training, patient care and quality control and four of the team operation processes: analysis, plan, do, check. CONCLUSION: The patient quality management model of the oral PACU is helpful for the professional identity and career development of stomatological anesthesia staff in China, which can accelerate the professional development of oral anesthesia nursing quality. According to the model, the patient's pain and fear will decrease, meanwhile, safety and comfort will increase. It can make contributions to the theoretical research and clinical practice in the future.

Characteristics of humoral and cellular responses to coronavirus disease 2019 (COVID-19) inactivated vaccine in central China: A prospective, multicenter, longitudinal study

Introduction In China, the long-term immunogenicity and adverse effects of inactivated vaccines produced by different or the same manufacturer remain unclear. Therefore, the objective of this study was to evaluate the cellular immune responses and neutralizing antibody kinetics of homologous and heterologous administrations of an inactivated coronavirus disease 2019 (COVID-19) vaccine 240 days after the second vaccination. Methods This prospective, multicenter, observational, longitudinal study involved 595 participants with a negative SARS-CoV-2 polymerase chain reaction result who were serologically tested and followed for 8 months after vaccination. Neutralizing antibodies, interferon-gamma (IFN-γ), interleukin (IL)-6, CD4+ T-lymphocyte, and B-lymphocyte counts were evaluated in serum samples after stimulation with 2 μg/mL SARS-CoV-2 spike protein for 16 h at follow-up intervals of 2 months. Results Most participants [582/595;146 male participants, 449 female participants;mean age 35 (26–50 years)] rapidly developed neutralizing antibodies after two doses of the vaccine administered 3-weeks apart. The positive rate of neutralizing antibodies peaked at 97.7% at 60–90 days, decreased, and stabilized at 82.9% at 181–240 days post-vaccination. Lower antibody concentrations were correlated with older age, longer duration after vaccination, non-health care workers, mixed-manufacturer vaccinations, and intervals of less than 40 days between two doses of vaccination, whereas lower IFN-γ levels and B-lymphocyte counts were associated with older age, blood type A, and non-health care workers. A higher IL-6 level was associated with older age, mixed-manufacturer vaccinations, intervals of less than 40 days between two doses of vaccination, and medical staff. Adverse reactions were mild or moderate and self-limited, with no serious events reported. Discussion Two doses of the Chinese inactivated vaccine induced robust and rapid antibody expression and cellular immune responses. Boosting vaccination is considered important, as antibodies and cellular immune responses were reduced in susceptible populations.

The Value of Peripheral Blood Cell Ratios in Primary Membranous Nephropathy: A Single Center Retrospective Study.

Background: Primary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults. Forty percent of the patients continue to progress and eventually develop into chronic renal failure. Although phospholipase A2 receptor (PLA2R) is the major antigen of PMN, the clinical features do not often parallel with the antibody titers. Therefore, it is significant to find relative credible markers to predict the treatment response. Methods: One hundred and eighteen PMN patients were recruited. The response to treatment was defined as ALB≥30g/L at 6 months and complete remission (CR) or not at the end of the follow-up. Renal outcome endpoint was defined as 50% or more Cr increase at the end. Results: The patients with poor treatment effects had numerically higher platelet-lymphocytes ratio (PLR). For patients with CR or not, the difference was near to statistic significant (P=0.095). When analyzing CR or not, the fitting of the binary logistic regression model including both PLA2R Ab titer and PLR (Hosmer-Lemeshow test: χ 2=8.328, P = 0.402; OR (PLA2R Ab titer) = 1.002 (95% CI 1.000-1.004, P = 0.042); OR (PLR) = 1.006 (95% CI 0.999-1.013, P = 0.098)) was markedly better than that with only PLA2R Ab titer (Hosmer-Lemeshow test: χ 2=13.885, P = 0.016). The patients with renal function deterioration showed significantly higher monocyte-lymphocyte ratio (MLR) (0.26 (0.22-0.31) vs 0.18 (0.13-0.22), P = 0.012). Conclusion: PMN patients with poor treatment response tended to have higher PLR at the time of renal biopsy, and a higher MLR was associated with poor renal outcomes. Our findings suggested that PLR and MLR might be used to predict treatment efficacy and prognosis for PMN patients, respectively.

Characteristics of humoral and cellular responses to coronavirus disease 2019 (COVID-19) inactivated vaccine in central China: A prospective, multicenter, longitudinal study.

Introduction: In China, the long-term immunogenicity and adverse effects of inactivated vaccines produced by different or the same manufacturer remain unclear. Therefore, the objective of this study was to evaluate the cellular immune responses and neutralizing antibody kinetics of homologous and heterologous administrations of an inactivated coronavirus disease 2019 (COVID-19) vaccine 240 days after the second vaccination. Methods: This prospective, multicenter, observational, longitudinal study involved 595 participants with a negative SARS-CoV-2 polymerase chain reaction result who were serologically tested and followed for 8 months after vaccination. Neutralizing antibodies, interferon-gamma (IFN-γ), interleukin (IL)-6, CD4+ T-lymphocyte, and B-lymphocyte counts were evaluated in serum samples after stimulation with 2 µg/mL SARS-CoV-2 spike protein for 16 h at follow-up intervals of 2 months. Results: Most participants [582/595; 146 male participants, 449 female participants; mean age 35 (26-50 years)] rapidly developed neutralizing antibodies after two doses of the vaccine administered 3-weeks apart. The positive rate of neutralizing antibodies peaked at 97.7% at 60-90 days, decreased, and stabilized at 82.9% at 181-240 days post-vaccination. Lower antibody concentrations were correlated with older age, longer duration after vaccination, non-health care workers, mixed-manufacturer vaccinations, and intervals of less than 40 days between two doses of vaccination, whereas lower IFN-γ levels and B-lymphocyte counts were associated with older age, blood type A, and non-health care workers. A higher IL-6 level was associated with older age, mixed-manufacturer vaccinations, intervals of less than 40 days between two doses of vaccination, and medical staff. Adverse reactions were mild or moderate and self-limited, with no serious events reported. Discussion: Two doses of the Chinese inactivated vaccine induced robust and rapid antibody expression and cellular immune responses. Boosting vaccination is considered important, as antibodies and cellular immune responses were reduced in susceptible populations.

The novel Nsp9-interacting host factor H2BE promotes PEDV replication by inhibiting endoplasmic reticulum stress-mediated apoptosis.

Porcine epidemic diarrhoea (PED) caused by porcine epidemic diarrhoea virus (PEDV) has led to significant economic losses in the swine industry worldwide. Histone Cluster 2, H2BE (HIST2H2BE), the main protein component in chromatin, has been proposed to play a key role in apoptosis. However, the relationship between H2BE and PEDV remains unclear. In this study, H2BE was shown to bind and interact with PEDV nonstructural protein 9 (Nsp9) via immunoprecipitation-mass spectrometry (IP-MS). Next, we verified the interaction of Nsp9 with H2BE by immunoprecipitation and immunofluorescence. H2BE colocalized with Nsp9 in the cytoplasm and nuclei. PEDV Nsp9 upregulated the expression of H2BE by inhibiting the expression of IRX1. We demonstrated that overexpression of H2BE significantly promoted PEDV replication, whereas knockdown of H2BE by small interfering RNA (siRNA) inhibited PEDV replication. Overexpression of H2BE led to significantly inhibited GRP78 expression, phosphorylated PERK (p-PERK), phosphorylated eIF2 (p-eIF2), phosphorylated IRE1 (p-IRE1), and phosphorylated JNK (p-JNK); negatively regulated CHOP and Bax expression and caspase-9 and caspase-3 cleavage; and promoted Bcl-2 production. Knocking down H2BE exerted the opposite effects. Furthermore, we found that after deletion of amino acids 1-28, H2BE did not promote PEDV replication. In conclusion, these studies revealed the mechanism by which H2BE is associated with ER stress-mediated apoptosis to regulate PEDV replication. Nsp9 upregulates H2BE. H2BE plays a role in inhibiting apoptosis and thus facilitating viral replication, which depends on the N-terminal region of H2BE (amino acids 1-28). These findings provide a reference for host-PEDV interactions and offer the possibility for developing strategies for PEDV decontamination and prevention.

GRAMD4 regulates PEDV-induced cell apoptosis inhibiting virus replication via the endoplasmic reticulum stress pathway.

Porcine epidemic diarrhea (PED) caused by the porcine epidemic diarrhea virus (PEDV) has caused huge losses in the swine industry worldwide. Glucosyltransferase Rab-like GTPase activator and myotubularin domain containing 4 (GRAMD4) is a proapoptotic protein, which replaced p53 inducing mitochondrial apoptosis. However, the relationship between GRAMD4 and PEDV has not been reported. Here, we aimed to investigate the potential role of GRAMD4 during PEDV infection. In this study, we used co-immunoprecipitation (co-IP) and mass spectrometry to identify GRAMD4 interaction with PEDV non-structural protein 6 (NSP6). Immunoprecipitation and laser confocal microscopy were utilized to demonstrate that GRAMD4 interacts with NSP6. NSP6 reduces GRAMD4 production through PERK and IRE1 pathway-mediated apoptosis. We demonstrated that overexpression of GRAMD4 effectively impaired the replication of PEDV, whereas knockdown of GRAMD4 facilitated the replication of PEDV. Overexpression of GRAMD4 increased GRP78, phosphorylated PERK (p-PERK), phosphorylated IRE1(p-IRE1) levels, promoted CHOP, phosphorylated JNK (p-JNK), Bax expression, caspase 9 and caspase 3 cleavage, and inhibited Bcl-2 production. Knockdown of GRAMD4 has the opposite effect. Finally, deletion of the GRAM domain of GRAMD4 cannot cause endoplasmic reticulum stress (ER stress)-mediated apoptosis and inhibit virus replication. In conclusion, these studies revealed the mechanism by which GRAMD4 was associated with ER stress and apoptosis regulating PEDV replication. NSP6 acted as a potential down-regulator of GRAMD4 and promoted the degradation of GRAMD4. GRAMD4 played a role in facilitating apoptosis and restricting virus replication, and the GRAM domain was required. These findings provided a reference for host-PEDV interactions and offered the possibility for PEDV decontamination and prevention.

Infection with wild-type SARS-CoV-2 elicits broadly neutralizing and protective antibodies against omicron subvariants.

The omicron variants of SARS-CoV-2 have substantial ability to escape infection- and vaccine-elicited antibody immunity. Here, we investigated the extent of such escape in nine convalescent patients infected with the wild-type SARS-CoV-2 during the first wave of the pandemic. Among the total of 476 monoclonal antibodies (mAbs) isolated from peripheral memory B cells, we identified seven mAbs with broad neutralizing activity to all variants tested, including various omicron subvariants. Biochemical and structural analysis indicated the majority of these mAbs bound to the receptor-binding domain, mimicked the receptor ACE2 and were able to accommodate or inadvertently improve recognition of omicron substitutions. Passive delivery of representative antibodies protected K18-hACE2 mice from infection with omicron and beta SARS-CoV-2. A deeper understanding of how the memory B cells that produce these antibodies could be selectively boosted or recalled can augment antibody immunity against SARS-CoV-2 variants.

Impact of COVID-19 pandemic on neuropathology service: Experience at one Canadian center.

The COVID-19 pandemic has had a significant impact on medical services. Many countries postponed nonemergent procedures to preserve hospital resources for the unprecedented situation. Surgical backlogs caused by the COVID-19 pandemic have been evaluated by different groups. However, the impact of this pandemic on pathology and specifically neuropathology (NP) services has received limited attention. In this study, we reviewed all NP reports of the London Health Sciences Centre from January 2018 (2 years before the pandemic declaration) until the end of the year 2021. Demographic information and pathology details were collected. For tumors, site, histopathology types, and WHO grading were analyzed. In nontumoral specimens, pathological diagnoses were compared in pre- and postpandemic time. The total number of NP samples reached its lowest in April 2020, corresponding to the first Ontario provincial lockdown, and fluctuated throughout the studied period. Among the different types of NP surgical specimens, muscle and epilepsy-related specimens showed a more significant reduction, compared to neoplastic specimens. In 2020, the proportion of tumor specimens from patients older than 40 years of age increased. Similarly, the proportion of high-grade glioma and brain metastasis diagnoses also increased. Lastly, we observed a marked increase in biopsies for temporal arteritis and other inflammatory lesions.

Digital Magnetic Detection of Biomolecular Interactions with Single Nanoparticles.

Biomolecular interactions compose a fundamental element of all life forms and are the biological basis of many biomedical assays. However, current methods for detecting biomolecular interactions have limitations in sensitivity and specificity. Here, using nitrogen-vacancy centers in diamond as quantum sensors, we demonstrate digital magnetic detection of biomolecular interactions with single magnetic nanoparticles (MNPs). We first developed a single-particle magnetic imaging (SiPMI) method on 100 nm-sized MNPs with negligible magnetic background, high signal stability, and accurate quantification. The single-particle method was performed on biotin-streptavidin interactions and DNA-DNA interactions in which a single-base mismatch was specifically differentiated. Subsequently, SARS-CoV-2-related antibodies and nucleic acids were examined by a digital immunomagnetic assay derived from SiPMI. In addition, a magnetic separation process improved the detection sensitivity and dynamic range by more than 3 orders of magnitude and also the specificity. This digital magnetic platform is applicable to extensive biomolecular interaction studies and ultrasensitive biomedical assays.