Transcatheter closure of multiple coronary artery fistulas: a coronary computed tomography angiography-based anatomic classification.

INTRODUCTION AND OBJECTIVES: This study aimed to retrospectively analyze the anatomical characteristics and classification of multiple coronary artery fistulas (MCAFs), and to compare the outcomes of transcatheter closure between MCAFs and single fistulas. METHODS: All patients who underwent attempts at transcatheter closure of coronary artery fistulas (CAFs) at Fuwai Hospital from 2010 to 2023 were retrospectively reviewed. Patients were categorized into single fistula and MCAFs groups, and anatomical characteristics and transcatheter closure outcomes were compared between the 2 groups. RESULTS: This retrospective study included 146 patients who underwent attempted transcatheter closure of CAFs, with a 14.38% failure rate. Among the 146 patients with CAFs, 32.19% were identified as having MCAFs, with types I, II, and III constituting 40.43%, 42.55%, and 17.02%, respectively. Unlike single fistulas, which predominantly originated from the right coronary artery and terminated in the left ventricle, MCAFs mainly had simultaneous origins from the right coronary artery and left anterior descending artery (29.79%), and predominantly drained into the pulmonary artery (70.21%), with a notable prevalence of plexus-like morphology (38.3% vs 2.02%, P < .001). The success rate of transcatheter closure was significantly lower for multiple fistulas compared with single fistula (64.29% vs 84.34%, P = .011). Multivariate regression analysis indicated that the risk of closure failure for MCAFs was 2.64 times that of single fistulas. CONCLUSIONS: MCAFs are common among CAFs and can be classified into 3 types based on the number and location of their origins and terminations. The risk of failure of transcatheter closure is significantly higher in MCAFs than in single fistulas.

Global trends in heart failure from 1990 to 2019: An age-period-cohort analysis from the Global Burden of Disease study.

AIMS: This study aimed to analyse the global prevalence and disability trends of heart failure (HF) from 1990 to 2019, considering both sexes and country-specific economic strata. METHODS: This study conducted a secondary analysis employing data from the Global Burden of Disease (GBD) study. The analysis is stratified by sex and Socio-demographic Index (SDI) levels. Through age-period-cohort and Joinpoint regression analyses, we investigated the temporal trends in HF prevalence and years lived with disability (YLDs) during this period. RESULTS: Between 1990 and 2019, the global prevalence of HF surged by 106.3% (95% uncertainty interval: 99.3% to 114.3%), reaching 56.2 million cases in 2019. While all-age prevalence and YLDs increased over the 30 year span, age-standardized rates decreased by 2019. Countries with higher SDI experienced a more pronounced percentage decrease compared with those with lower SDI. Longitudinal analysis revealed an overall improvement in both prevalence and YLDs for HF, albeit with notable disparities between SDI quintiles and sexes. Ischaemic heart disease and hypertensive heart disease emerged as the most rapidly increasing and primarily contributing causes of HF, albeit with variations observed across different countries. The average annual percentage change for prevalence and YLDs over the period was -0.26% and -0.25%, respectively. CONCLUSIONS: This study offers valuable insights into the global burden of HF, considering factors such as population aging, regional disparities, sex differences and aetiological variations. The findings hold significant implications for healthcare planning and resource allocation. Continued assessment of these trends and innovative strategies for HF prevention and management are crucial for addressing this pressing global health concern.

Outcomes of Transcatheter Closure of Congenital Left Circumflex Coronary Artery Fistula.

BACKGROUND: Congenital left circumflex coronary artery fistula (LCX-CAF) is a relatively rare type of coronary artery fistula (CAF); little is known about the outcomes of transcatheter closure (TCC) of LCX-CAF.Methods and Results: All consecutive patients admitted to Fuwai Hospital and scheduled for TCC of LCX-CAF between January 2012 and December 2022 were reviewed retrospectively. Of the 25 consecutive patients (mean [±SD] age 34±20 years; 48% male) admitted and scheduled for TCC of congenital LCX-CAF, the procedure was feasible in 22 (77.3%). The mean (±SD) diameter of the fistulas was 6.99±2.04 mm; 21 (84%) patients had a large fistula (i.e., diameter >2-fold greater than non-feeding coronary artery). Occluders were deployed via a transarterial approach and arteriovenous loop in 6 (27.3%) and 16 (72.7%) patients, respectively. No procedural complications were recorded. Although the procedural success rates are similar for single LCX-CAF and left anterior descending CAF (81.25% vs. 92.86%; P=0.602), the mean time from initial angiography to first occluder deployment is significantly longer for LCX-CAF (83.06±36.07 vs. 36.00±9.49 min; P<0.001). The mean (±SD) follow-up time was 62.2±45.5 months. The incidence of myocardial infarction and recanalization of the fistula was 4.5% (1/22) and 9.1% (2/22), respectively. CONCLUSIONS: TCC of LCX-CAF is a feasible and effective alternative to surgical repair, with comparable outcomes in selected patients. Optimal medical therapy to prevent post-closure myocardial infarction requires further investigation.

SARS-CoV-2 spike glycosylation affects function and neutralization sensitivity.

The glycosylation of viral envelope proteins can play important roles in virus biology and immune evasion. The spike (S) glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) includes 22 N-linked glycosylation sequons and 17 O-linked glycosites. We investigated the effect of individual glycosylation sites on SARS-CoV-2 S function in pseudotyped virus infection assays and on sensitivity to monoclonal and polyclonal neutralizing antibodies. In most cases, the removal of individual glycosylation sites decreased the infectiousness of the pseudotyped virus. For glycosylation mutants in the N-terminal domain and the receptor-binding domain (RBD), reduction in pseudotype infectivity was predicted by a commensurate reduction in the level of virion-incorporated S protein and reduced S trafficking to the cell surface. Notably, the presence of a glycan at position N343 within the RBD had diverse effects on neutralization by RBD-specific monoclonal antibodies cloned from convalescent individuals. The N343 glycan reduced the overall sensitivity to polyclonal antibodies in plasma from COVID-19 convalescent individuals, suggesting a role for SARS-CoV-2 S glycosylation in immune evasion. However, vaccination of convalescent individuals produced neutralizing activity that was resilient to the inhibitory effect of the N343 glycan.IMPORTANCEThe attachment of glycans to the spike proteins of viruses during their synthesis and movement through the secretory pathway can affect their properties. This study shows that the glycans attached to the severe acute respiratory syndrome coronavirus-2 spike protein enable its movement to the cell surface and incorporation into virus particles. Certain glycans, including one that is attached to asparagine 343 in the receptor-binding domain of the spike protein, can also affect virus neutralization by antibodies. This glycan can increase or decrease sensitivity to individual antibodies, likely through direct effects on antibody epitopes and modulation of spike conformation. However, the overall effect of the glycan in the context of the polyclonal mixture of antibodies in convalescent serum is to reduce neutralization sensitivity. Overall, this study highlights the complex effects of glycosylation on spike protein function and immune evasion.

Biodegradable Cardiac Occluder with Surface Modification by Gelatin-Peptide Conjugate to Promote Endogenous Tissue Regeneration.

Transcatheter intervention has been the preferred treatment for congenital structural heart diseases by implanting occluders into the heart defect site through minimally invasive access. Biodegradable polymers provide a promising alternative for cardiovascular implants by conferring therapeutic function and eliminating long-term complications, but inducing in situ cardiac tissue regeneration remains a substantial clinical challenge. PGAG (polydioxanone/poly (l-lactic acid)-gelatin-A5G81) occluders are prepared by covalently conjugating biomolecules composed of gelatin and layer adhesive protein-derived peptides (A5G81) to the surface of polydioxanone and poly (l-lactic acid) fibers. The polymer microfiber-biomacromolecule-peptide frame with biophysical and biochemical cues could orchestrate the biomaterial-host cell interactions, by recruiting endogenous endothelial cells, promoting their adhesion and proliferation, and polarizing immune cells into anti-inflammatory phenotypes and augmenting the release of reparative cytokines. In a porcine atrial septal defect (ASD) model, PGAG occluders promote in situ tissue regeneration by accelerating surface endothelialization and regulating immune response, which mitigate inflammation and fibrosis formation, and facilitate the fusion of occluder with surrounding heart tissue. Collectively, this work highlights the modulation of cell-biomaterial interactions for tissue regeneration in cardiac defect models, ensuring endothelialization and extracellular matrix remodeling on polymeric scaffolds. Bioinspired cell-material interface offers a highly efficient and generalized approach for constructing bioactive coatings on medical devices.

Organic-Inorganic Rare-Earth Double Perovskite Ferroelectric with Large Piezoelectric Response and Ferroelasticity for Flexible Composite Energy Harvesters.

Hybrid organic-inorganic perovskite (HOIP) ferroelectric materials have great potential for developing self-powered electronic transducers owing to their impressive piezoelectric performance, structural tunability and low processing temperatures. Nevertheless, their inherent brittle and low elastic moduli limit their application in electromechanical conversion. Integration of HOIP ferroelectrics and soft polymers is a promising solution. In this work, a hybrid organic-inorganic rare-earth double perovskite ferroelectric, [RM3HQ]2RbPr(NO3)6 (RM3HQ = (R)-N-methyl-3-hydroxylquinuclidinium) is presented, which possesses multiaxial nature, ferroelasticity and satisfactory piezoelectric properties, including piezoelectric charge coefficient (d33) of 102.3 pC N-1 and piezoelectric voltage coefficient (g33) of 680 × 10-3 V m N-1. The piezoelectric generators (PEG) based on composite films of [RM3HQ]2RbPr(NO3)6@polyurethane (PU) can generate an open-circuit voltage (Voc) of 30 V and short-circuit current (Isc) of 18 µA, representing one of the state-of-the-art PEGs to date. This work has promoted the exploration of new HOIP ferroelectrics and their development of applications in electromechanical conversion devices.

Alerting trends in epidemiology for non-rheumatic degenerative mitral valve disease, 1990-2019: An age-period-cohort analysis for the Global Burden of Disease Study 2019.

BACKGROUND: The global and national burden of rheumatic mitral valve disease (MVD) has been well studied and estimated before. However, little is known about non-rheumatic degenerative MVD. Therefore, this study aimed to assess the trends in non-rheumatic degenerative MVD (NRDMVD) epidemiology, with an emphasis on NRDMVD mortality, leading risk factors, and their associations with age, period, and birth cohort. METHODS: Using the data derived from the Global Burden of Disease Study 2019, including prevalence, mortality, and disability-adjusted life years, we analyzed the burden of NRDMVD and the detailed trends of NRDMVD mortality over the past 30 years in 204 countries and territories by implementing the age-period-cohort framework. RESULTS: Globally, the number of deaths due to NRDMVD increased from 5695.89 (95% uncertainty interval [UI]: 5405.19 to 5895.4) × 1000 in 1990 to 9137.79 (95% UI: 8395.68 to 9743.55) × 1000 in 2019. The all-age mortality rate increased from 106.47 (95% UI: 101.03 to 110.2) per 100,000 to 118.1 (95% UI: 108.51 to 125.93) per 100,000, whereas the age-standardized mortality rate decreased from 170.45 (95% UI: 159.61 to 176.94) per 100,000 to 117.95 (95% UI: 107.83 to 125.92) per 100,000. The estimated net drift of mortality per year was -1.1% (95% confidence interval: -1.17 to -1.04). The risk of death due to NRDMVD increased with age, reaching its peak after 85 years old globally. Despite female patients being associated with lower local drift than male patients, no significant gender differences were observed in the age effect across countries and regions for all sociodemographic index (SDI) levels, except low-SDI regions. CONCLUSIONS: We estimated the global disease prevalence of and mortality due to NRDMVD over approximately a 30-year period. The health-related burden of NRDMVD has declined worldwide; however, the condition persisted in low-SDI regions. Moreover, higher attention should be paid to female patients.

Study design and rationale of COMPETE: Comparison of the effect of medication therapy in alleviating migraine with patent foramen ovale.

BACKGROUND: Previous studies have examined the impact of antithrombotic agents on Patent Foramen Ovale (PFO) in relation to migraine. However, differences in effectiveness of different antithrombotic agents and traditional migraine medications are not known. METHODS/DESIGN: This study is an investigator-initiated, randomized, multicenter, single-masked (outcomes assessor), and active-controlled parallel-group trial (ClinicalTrials.gov Identifier: NCT05546320), with the objective of evaluating the prevention efficacy of antithrombotic agents compared to first-line migraine medication in PFO patients. The trial involves 1,000 migraine patients with a right-to-left shunt at the atrial level, randomized in a 1:1:1:1 fashion to receive either aspirin 300 mg QD, clopidogrel 75 mg QD, rivaroxaban 20 mg QD, or the active-control metoprolol 25 mg BID. The primary efficacy end point is the response rate, defined as a 50% or greater reduction in the average migraine attack days per month or in the average number of migraine attacks per month at 12-week visit compared to baseline. CONCLUSIONS: The COMPETE trial aims to provide valuable insights into the comparative effectiveness of antithrombotic agents and standard migraine therapies in patients with PFO. This study holds the promise of advancing treatment approaches for individuals having migraines associated with PFO, thus addressing an important gap in current migraine management strategies.

Noncontact remote sensing of abnormal blood pressure using a deep neural network: a novel approach for hypertension screening.

Background: As the global burden of hypertension continues to increase, early diagnosis and treatment play an increasingly important role in improving the prognosis of patients. In this study, we developed and evaluated a method for predicting abnormally high blood pressure (HBP) from infrared (upper body) remote thermograms using a deep learning (DL) model. Methods: The data used in this cross-sectional study were drawn from a coronavirus disease 2019 (COVID-19) pilot cohort study comprising data from 252 volunteers recruited from 22 July to 4 September 2020. Original video files were cropped at 5 frame intervals to 3,800 frames per slice. Blood pressure (BP) information was measured using a Welch Allyn 71WT monitor prior to infrared imaging, and an abnormal increase in BP was defined as a systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg. The PanycNet DL model was developed using a deep neural network to predict abnormal BP based on infrared thermograms. Results: A total of 252 participants were included, of which 62.70% were male and 37.30% were female. The rate of abnormally high HBP was 29.20% of the total number. In the validation group (upper body), precision, recall, and area under the receiver operating characteristic curve (AUC) values were 0.930, 0.930, and 0.983 [95% confidence interval (CI): 0.904-1.000], respectively, and the head showed the strongest predictive ability with an AUC of 0.868 (95% CI: 0.603-0.994). Conclusions: This is the first technique that can perform screening for hypertension without contact using existing equipment and data. It is anticipated that this technique will be suitable for mass screening of the population for abnormal BP in public places and home BP monitoring.

Genetic overlap for ten cardiovascular diseases: A comprehensive gene-centric pleiotropic association analysis and Mendelian randomization study.

Recent studies suggest that pleiotropic effects may explain the genetic architecture of cardiovascular diseases (CVDs). We conducted a comprehensive gene-centric pleiotropic association analysis for ten CVDs using genome-wide association study (GWAS) summary statistics to identify pleiotropic genes and pathways that may underlie multiple CVDs. We found shared genetic mechanisms underlying the pathophysiology of CVDs, with over two-thirds of the diseases exhibiting common genes and single-nucleotide polymorphisms (SNPs). Significant positive genetic correlations were observed in more than half of paired CVDs. Additionally, we investigated the pleiotropic genes shared between different CVDs, as well as their functional pathways and distribution in different tissues. Moreover, six hub genes, including ALDH2, XPO1, HSPA1L, ESR2, WDR12, and RAB1A, as well as 26 targeted potential drugs, were identified. Our study provides further evidence for the pleiotropic effects of genetic variants on CVDs and highlights the importance of considering pleiotropy in genetic association studies.

A generalized deep learning model for heart failure diagnosis using dynamic and static ultrasound.

Objective: Echocardiography (ECG) is the most common method used to diagnose heart failure (HF). However, its accuracy relies on the experience of the operator. Additionally, the video format of the data makes it challenging for patients to bring them to referrals and reexaminations. Therefore, this study used a deep learning approach to assist physicians in assessing cardiac function to promote the standardization of echocardiographic findings and compatibility of dynamic and static ultrasound data. Methods: A deep spatio-temporal convolutional model r2plus1d-Pan (trained on dynamic data and applied to static data) was improved and trained using the idea of "regression training combined with classification application," which can be generalized to dynamic ECG and static cardiac ultrasound views to identify HF with a reduced ejection fraction (EF < 40%). Additionally, three independent datasets containing 8976 cardiac ultrasound views and 10085 cardiac ultrasound videos were established. Subsequently, a multinational, multi-center dataset of EF was labeled. Furthermore, model training and independent validation were performed. Finally, 15 registered ultrasonographers and cardiologists with different working years in three regional hospitals specialized in cardiovascular disease were recruited to compare the results. Results: The proposed deep spatio-temporal convolutional model achieved an area under the receiveroperating characteristic curve (AUC) value of 0.95 (95% confidence interval [CI]: 0.947 to 0.953) on the training set of dynamic ultrasound data and an AUC of 1 (95% CI, 1 to 1) on the independent validation set. Subsequently, the model was applied to the static cardiac ultrasound view (validation set) with simultaneous input of 1, 2, 4, and 8 images of the same heart, with classification accuracies of 85%, 81%, 93%, and 92%, respectively. On the static data, the classification accuracy of the artificial intelligence (AI) model was comparable with the best performance of ultrasonographers and cardiologists with more than 3 working years (P = 0.344), but significantly better than the median level (P = 0.0000008). Conclusion: A new deep spatio-temporal convolution model was constructed to identify patients with HF with reduced EF accurately (< 40%) using dynamic and static cardiac ultrasound images. The model outperformed the diagnostic performance of most senior specialists. This may be the first HF-related AI diagnostic model compatible with multi-dimensional cardiac ultrasound data, and may thereby contribute to the improvement of HF diagnosis. Additionally, the model enables patients to carry "on-the-go" static ultrasound reports for referral and reexamination, thus saving healthcare resources.

Comparison of self- and balloon-expandable valves in patients with dilatated ascending aorta undergoing transcatheter aortic valve replacement.

Background: Limited studies have focused on the performance of self-expandable valves (SEVs) and balloon-expandable valves (BEVs) in patients with dilatated ascending aorta (AA) undergoing transcatheter aortic valve replacement (TAVR). The present study compared the performance of widely used Edwards BEVs and domestic SEVs in patients with dilatated AA among Chinese population. Methods: We identified and reviewed 207 patients who had baseline AA diameter ≥40 mm and underwent transfemoral TAVR. Patients were divided into two groups: SEV and BEV. The SEVs were locally manufactured valves that have received Chinese regulatory approval (Venus-A, Taurus One, and VitaFlow), while the BEVs were Edwards Sapien XT and Sapien3. Procedural device success and post-procedural changes of AA diameters were compared. Results: The sample size of SEV group was larger than that of BEV group because BEVs were not available in China in the early clinical practice. The overall device success was slightly lower in SEV group compared with BEV group (84.2% vs. 95.8%, P=0.213). However, in the univariable and multivariable logistic regression analyses, only bicuspid aortic valve (BAV) was found to be an independent risk factor for device failure (OR: 2.632, CI: 1.107-6.257, P=0.029). During the median follow-up of 21 months, no statistical difference was found between the two groups regarding the overall survival (83.1%±4.7% vs. 95.8%±4.1%, P=0.533), and no aortic dissection nor rupture was observed. In a subgroup of patients who had follow-up CTs ≥12-month intervals, the AA diameter appeared to remain stable in SEV group with an aortic expansion rate of 0 (-0.4 to 0.8) mm (P=0.102), while it slightly enlarged in BEV group with an aortic expansion rate of 0.4 (-0.4 to 0.6) mm/y (P=0.038). In addition, the AA diameter also slightly enlarged in patients with BAV [0.2 (0 to 1.0) mm/y, P=0.015], while it remained stable in patients with tricuspid aortic valve (TAV) [0 (-0.8 to 0.6) mm/y, P=0.640]. Conclusions: In patients with dilatated AA who underwent TAVR, the type of THVs did not affect the procedural device success. BAV appeared to be a risk factor for both device failure and higher aortic expansion rate in these patients.

The Cardiovascular Disease Burden Attributable to Low Physical Activity in the Western Pacific Region, 1990-2019: an Age-Period-Cohort Analysis of the Global Burden of Disease Study.

AIM: To increase the comprehensive understanding of trends in the burden of cardiovascular disease (CVD) attributable to low physical activity in the Western Pacific Region. METHODS: Based on data from the Global Burden of Disease (GBD) study for the years 1990-2019, an age-period-cohort (APC) analysis was conducted to investigate trends in CVD-related mortality attributable to low physical activity in the Western Pacific Region and associations with age, period, and birth cohort. We also used joinpoint regression analysis to identify the periods with the most substantial changes. RESULTS: The Western Pacific Region witnessed a substantial increase in CVD deaths attributable to low physical activity, accompanied by a rise in all-age CVD-related mortality. However, the age-standardized death rate was lower in the region than the global level, highlighting the importance of considering the age composition of CVD burden in the region. Countries with higher SDI levels exhibited lower mortality than those with lower SDI levels. The longitudinal analysis using the APC model indicated an overall improvement in CVD-related mortality attributable to low physical activity in the region, but with differences between sexes and CVD subtypes. Specific period in which CVD-related mortality decreased significantly were 2011-2016, for the average annual percentage change for the period was -0.69%. CONCLUSION: The study highlights the significance of addressing low physical activity as a modifiable risk factor for CVD burden in the Western Pacific Region. Further research is essential to understand the factors contributing to inter-country variations, sex disparities, and CVD subtypes distinctions.

Feasibility and safety of a percutaneous and non-fluoroscopic procedure for left atrial appendage closure in patients for whom fluoroscopy presents risk: a cohort study.

Background: Most patients undergoing left atrial appendage closure (LAAC) are older adult individuals with atrial fibrillation (AF) and many comorbidities, which may elevate the risk for complications associated with contrast agents with the fluoroscopic image-guided procedure. This retrospective cohort study of patients with AF at high risk for use of contrast agents compared the feasibility and safety of LAAC using percutaneous and non-fluoroscopic procedure with transesophageal echocardiography (TEE) as the only image guidance relative to those under fluoroscopic image guidance. Methods: In this retrospective study, we enrolled 126 patients with AF who underwent LAAC from September 2017 to December 2020. Patients were divided into 2 groups based on the imaging guidance modality: a TEE group (n=32) and a fluoroscopic group (n=94). We analyzed the differences in complete closure rates and device- and procedure-related complications between the 2 groups. Continuous variables were assessed using the Student t-test or Mann-Whitney test, while categorical variables were evaluated using Pearson chi-squared test or Fisher exact test. Propensity-score matching was used to adjust for baseline differences. Results: Propensity-score matching yielded 25 pairs of patients with similarly distributed age (72.9±6.9 vs. 73.1±4.9 years; P=0.925), gender (10:15 vs. 11:14; P>0.99), weight (68.3±11.2 vs. 68.1±12.3 kg; P=0.948), and alanine aminotransferase level (20.0±9.8 vs. 22.5±14.2 U/L; P=0.482). The LAA was successfully occluded in all patients, and the TEE group showed similar results to the fluoroscopic group in terms of success rate (100% vs. 100%; P>0.99) and hospitalization duration [5.0 (IQ1-IQ3: 3.0-7.0) vs. 5.0 (IQ1-IQ3: 3.0-6.0) days; P=0.498]. The groups also demonstrated comparable complication rates, with 1 (4.2%) case of pericardial effusion and 1 (4.2%) case of residual shunt in the TEE group, and 5 (20%) cases of residual shunt, 1 (4.2%) case of pericardial effusion, 1 (4.2%) case of myocardial infarction, and 1 (4.2%) case of access-related complications in the fluoroscopic group. There were no deaths. The overall incidence rate of procedure-related complications (6.2% vs. 18.1%, P=0.153) at mean 22.2±4.5 months follow-up between the 2 groups was similar. Conclusions: In patients with AF of high risk for use of contrast agents, LAAC under non-fluoroscopic guidance appears feasible and safe with similar outcomes to that under fluoroscopic guidance.

SARS-CoV-2 spike glycosylation affects function and neutralization sensitivity.

The glycosylation of viral envelope proteins can play important roles in virus biology and immune evasion. The spike (S) glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) includes 22 N-linked glycosylation sequons and 17 O-linked glycosites. Here, we investigated the effect of individual glycosylation sites on SARS-CoV-2 S function in pseudotyped virus infection assays and on sensitivity to monoclonal and polyclonal neutralizing antibodies. In most cases, removal of individual glycosylation sites decreased the infectiousness of the pseudotyped virus. For glycosylation mutants in the N-terminal domain (NTD) and the receptor binding domain (RBD), reduction in pseudotype infectivity was predicted by a commensurate reduction in the level of virion-incorporated spike protein. Notably, the presence of a glycan at position N343 within the RBD had diverse effects on neutralization by RBD-specific monoclonal antibodies (mAbs) cloned from convalescent individuals. The N343 glycan reduced overall sensitivity to polyclonal antibodies in plasma from COVID-19 convalescent individuals, suggesting a role for SARS-CoV-2 spike glycosylation in immune evasion. However, vaccination of convalescent individuals produced neutralizing activity that was resilient to the inhibitory effect of the N343 glycan.

Cyantraniliprole seed treatment effectively controls wireworms (Pleonomus canaliculatus Faldermann) and white grubs (Anomala corpulenta Motschulsky) in maize fields.

Wireworms and white grubs are destructive underground pests in maize fields in China. Cyantraniliprole has good control effect on coleoptera pests. Here, we evaluated the toxicity of cyantraniliprole to the second instar larvae of Anomala corpulenta Motschulsky and third-instar of larvae of Pleonomus canaliculatus Faldermann and the effects of sublethal concentrations on the activity of antioxidant and detoxification enzymes. We also explored the efficacy of cyantraniliprole on underground pests under indoor and field conditions. The LC50 of cyantraniliprole for the third instar larvae of P. canaliculatus was 23.3712 mg/L, and that for the second instar larvae of A. corpulenta was 5.9715 mg/L. Cyantraniliprole can activate the activity of superoxide dismutase (SOD), peroxidase (POD), and glutathione S-transferase (GST) to different degrees at a sublethal dose. According to the pot experiment and the control efficacy test in the field, the indoor control effect of cyantraniliprole seed treatment on P. canaliculatus and white grubs was approximately 80%, and the maximum increase in yield achieved through cyantraniliprole application was approximately 15% in the field efficacy test. Cyantraniliprole has a strong control effect on wireworms and white grubs, so it can be used to treat seeds to control underground pests in maize fields.

Development of an Expert-Level Right Ventricular Abnormality Detection Algorithm Based on Deep Learning.

PURPOSE: Studies relating to the right ventricle (RV) are inadequate, and specific diagnostic algorithms still need to be improved. This essay is designed to make exploration and verification on an algorithm of deep learning based on imaging and clinical data to detect RV abnormalities. METHODS: The Automated Cardiac Diagnosis Challenge dataset includes 20 subjects with RV abnormalities (an RV cavity volume which is higher than 110 mL/m2 or RV ejection fraction which is lower than 40%) and 20 normal subjects who suffered from both cardiac MRI. The subjects were separated into training and validation sets in a ratio of 7:3 and were modeled by utilizing a nerve net of deep-learning and six machine-learning algorithms. Eight MRI specialists from multiple centers independently determined whether each subject in the validation group had RV abnormalities. Model performance was evaluated based on the AUC, accuracy, recall, sensitivity and specificity. Furthermore, a preliminary assessment of patient disease risk was performed based on clinical information using a nomogram. RESULTS: The deep-learning neural network outperformed the other six machine-learning algorithms, with an AUC value of 1 (95% confidence interval: 1-1) on both training group and validation group. This algorithm surpassed most human experts (87.5%). In addition, the nomogram model could evaluate a population with a disease risk of 0.2-0.8. CONCLUSIONS: A deep-learning algorithm could effectively identify patients with RV abnormalities. This AI algorithm developed specifically for right ventricular abnormalities will improve the detection of right ventricular abnormalities at all levels of care units and facilitate the timely diagnosis and treatment of related diseases. In addition, this study is the first to validate the algorithm's ability to classify RV abnormalities by comparing it with human experts.

Irreversible Inactivation of SARS-CoV-2 by Lectin Engagement with Two Glycan Clusters on the Spike Protein.

Host cell infection by SARS-CoV-2, similar to that by HIV-1, is driven by a conformationally metastable and highly glycosylated surface entry protein complex, and infection by these viruses has been shown to be inhibited by the mannose-specific lectins cyanovirin-N (CV-N) and griffithsin (GRFT). We discovered in this study that CV-N not only inhibits SARS-CoV-2 infection but also leads to irreversibly inactivated pseudovirus particles. The irreversibility effect was revealed by the observation that pseudoviruses first treated with CV-N and then washed to remove all soluble lectin did not recover infectivity. The infection inhibition of SARS-CoV-2 pseudovirus mutants with single-site glycan mutations in spike suggested that two glycan clusters in S1 are important for both CV-N and GRFT inhibition: one cluster associated with the RBD (receptor binding domain) and the second with the S1/S2 cleavage site. We observed lectin antiviral effects with several SARS-CoV-2 pseudovirus variants, including the recently emerged omicron, as well as a fully infectious coronavirus, therein reflecting the breadth of lectin antiviral function and the potential for pan-coronavirus inactivation. Mechanistically, observations made in this work indicate that multivalent lectin interaction with S1 glycans is likely a driver of the lectin infection inhibition and irreversible inactivation effect and suggest the possibility that lectin inactivation is caused by an irreversible conformational effect on spike. Overall, lectins' irreversible inactivation of SARS-CoV-2, taken with their breadth of function, reflects the therapeutic potential of multivalent lectins targeting the vulnerable metastable spike before host cell encounter.

Method validation and dissipation kinetics of the novel HPPD-inhibiting herbicide cypyrafluone in winter wheat using QuEChERS method coupled with UPLC-MS/MS.

Cypyrafluone, a novel hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicide, can successfully control a wide species of grass and broadleaf weed in wheat fields. However, the dissipation behaviors and terminal residues of cypyrafluone in wheat fields remain unclear. Here, a simple, accurate, and dependable approach for the analysis of cypyrafluone in soil, wheat plant, and grain was constructed utilizing an adapted QuEChERS extraction combined with UPLC-MS/MS. For accurate quantification, matrix-matched calibrations with high linearity (R2 >0.99) were employed to eliminate matrix interference. The method possessed high accuracy with recoveries in the range of 85.5%- 100.6% and precision with relative standard deviations < 14.3%, as well as high sensitivity with limits of quantifications of 0.001 mg kg-1 in the three matrixes. The dissipation kinetics and terminal residues of cypyrafluone were determined at two separate locations with different climates, soil types and cropping systems in 2018. The half-lives of cypyrafluone in soil and wheat plant were 1.47-1.55 d and 1.00-1.03 d, respectively. At harvest, the terminal residue values of cypyrafluone detected in wheat plants were 0-0.0025 mg kg-1 and 0.0044-0.0057 mg kg-1 at the recommended dose and 1.5 times of the recommended dose, respectively, and 0.0049 mg kg-1 of this herbicide was detected in grain at 1.5 times of the recommended dose, which was below the maximum residue limit (MRL). Finally, the risk quotient for cypyrafluone ranged from 0.33% to 0.81% (<1) for different age groups in China, indicating that the impact of residues from the cypyrafluone application on wheat was acceptable. These findings above will offer scientific guidelines for cypyrafluone application in the wheat field ecosystem.