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Abstract Background Abnormal blood flow patterns are known to contribute to the ascending aortic dilation in patients with bicuspid aortic valve (BAV). The present study elucidated the blood flow characteristics in the dilated ascending aorta before and after transcatheter aortic valve replacement (TAVR) using computational fluid dynamics (CFD) analysis. Methods We performed CFD analysis in three BAV patients with ascending aortic dilation (maximum diameter ≥ 45 mm) who underwent TAVR. The blood flow streamline was visualized to evaluate the pre- and post-operative flow velocity, severity of vortex and helix, and wall shear stress (WSS) in the ascending aorta. Results Before the procedure, all three patients showed abnormal blood flow patterns, with vortex and helix in the ascending aorta. Regionally elevated WSS was also observed in the lateral or posterior ascending aortic wall (16.7 Pa, 12.2 Pa, and 14.5 Pa in patient 1, 2, and 3, respectively). After the procedure, the blood flow patterns significantly improved, and the maximum WSS also decreased (4.2 Pa, 1.1 Pa, and 3.2 Pa in patient 1, 2, and 3, respectively). Conclusion Abnormal blood flow patterns and WSS appeared to improve after TAVR in BAV patients with ascending aortic dilation. The impact on the long-term aortic growth rate and the incidence of aortic dissection requires further studies. Trial Registration Changes of Ascending Aortic Diameter in Patients Undergoing Transcatheter Aortic Valve Replacement. ClinicalTrial.gov number NCT05739253. Trial registration date 20,230,212.

Abstract 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.

Background: Tricuspid transcatheter edge-to-edge repair (T-TEER) has emerged as an attractive option for severe tricuspid regurgitation (TR). To avoid the radiation exposure for both patients and medical staff, we propose a sole-echocardiography-guided method for T-TEER. The purpose of this article was to investigate the feasibility of sole-echocardiography-guided T-TEER. Methods: This was a retrospective observational study, including 43 patients who underwent sole-echocardiography-guided T-TEER at two medical centers in China between June 2022 and September 2023. Clinical and echocardiographic data were collected at baseline, discharge and 6-month follow-up. Results: Patients enrolled in this study were elderly (71.6 ± 8.2 years) with significant comorbidities, 67.4% had baseline massive or torrential TR and 76.7% were classified as New York Heart Association (NYHA) functional class III/IV. All patients achieved successful device implantation, and no severe device-related complications or mortality occurred during the follow-up period. Significantly reduced TR and reversed right ventricular remodeling were observed at 6-month follow-ups. Patients classified as NYHA functional class I/II increased from 23.3% at baseline to 81.4% at 6-month follow-up (p < 0.001). Conclusions: Sole-echocardiography-guided T-TEER has a low incidence of complications and can effectively reduce TR. It is feasible to substitute conventional fluoroscopy and echocardiography guidance for echocardiography guidance alone. Further large-scale randomized controlled trials are needed to validate the safety, efficacy and patient benefits of this technique.

In regions with limited resources and moderate incomes, the relentless spectre of cardiovascular diseases (CVDs) continues to loom large. Amidst this challenge, the precise classification of heart sounds is emerging as a pivotal linchpin in the realm of early CVD diagnosis and intervention. Manual heart sound auscultation efficacy remains tethered to the expertise of physicians, but the tides are shifting. With deep learning algorithms, heart sound classification reaches new heights. In this paradigm-shifting article, we unveil an ingenious model fortified by bispectrum-inspired feature extraction and the cutting-edge prowess of the Vision Transformer (ViT) model. This model spearheads the binary classification of heart sounds, labelling them as either 'normal' or 'abnormal.' Our model uses data from the PhysioNet Challenge 2022 database, which contains 3163 data points from 942 patients. The model showcases an adept classification process with a remarkable consistency, notably holding its own when distinguishing between heart sounds of pregnant and nonpregnant patients. Moreover, we dare to challenge the status quo. This article boldly pits the performance of our model against that of seasoned cardiologists. Our model emerges as the triumphant frontrunner, eclipsing the proficiency of even the most seasoned cardiologists. In a world where health resources are unevenly distributed, this pioneering work offers a beacon of hope, unlocking a future where advanced algorithms not only match but surpass human expertise. Step into the forefront of transformative cardiac care—where artificial intelligence becomes the key to unravelling the secrets of heart sounds.

ABSTRACT 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.

Ventricular septal defect (VSD) is one of the commonest congenital heart diseases (CHDs). Current occluders for VSD treatment are mainly made of nitinol, which has the risk of nickel allergy, persistent myocardial abrasion and fatal arrythmia. Herein, a fully biodegradable polydioxanone (PDO) occluder equipped with a shape line and poly-l-lactic acid PLLA membranes is developed for VSD closure without the addition of metal marker. PDO occluder showed great mechanical strength, fatigue resistance, geometry fitness, biocompatibility and degradability. In a rat subcutaneous implantation model, PDO filaments significantly alleviated inflammation response, mitigated fibrosis and promoted endothelialization compared with nitinol. The safety and efficacy of PDO occluder were confirmed in a canine VSD model with 3-year follow-up, demonstrating the biodegradable PDO occluder could not only effectively repair VSD, induce cardiac remodeling but also address the complications associated with metal occluders. Furthermore, a pilot clinical trial with five VSD patients indicated that all the occluders were successfully implanted under the guidance of echocardiography and no adverse events occurred during the 3-month follow-up. Collectively, the fully bioresorbable PDO occluder is safe and effective for clinical VSD closure and holds great promise for the treatment of structural CHDs.

Abstract 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.

Problem: Chest radiography is a crucial tool for diagnosing thoracic disorders, but interpretation errors and a lack of qualified practitioners can cause delays in treatment. Aim: This study aimed to develop a reliable multi-classification artificial intelligence (AI) tool to improve the accuracy and efficiency of chest radiograph diagnosis. Methods: We developed a convolutional neural network (CNN) capable of distinguishing among 26 thoracic diagnoses. The model was trained and externally validated using 795,055 chest radiographs from 13 datasets across 4 countries. Results: The CNN model achieved an average area under the curve (AUC) of 0.961 across all 26 diagnoses in the testing set. COVID-19 detection achieved perfect accuracy (AUC 1.000, [95% confidence interval {CI}, 1.000 to 1.000]), while effusion or pleural effusion detection showed the lowest accuracy (AUC 0.8453, [95% CI, 0.8417 to 0.8489]). In external validation, the model demonstrated strong reproducibility and generalizability within the local dataset, achieving an AUC of 0.9634 for lung opacity detection (95% CI, 0.9423 to 0.9702). The CNN outperformed both radiologists and nonradiological physicians, particularly in trans-device image recognition. Even for diseases not specifically trained on, such as aortic dissection, the AI model showed considerable scalability and enhanced diagnostic accuracy for physicians of varying experience levels (all P < 0.05). Additionally, our model exhibited no gender bias (P > 0.05). Conclusion: The developed AI algorithm, now available as professional web-based software, substantively improves chest radiograph interpretation. This research advances medical imaging and offers substantial diagnostic support in clinical settings.

Summary: 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.

Abstract The treatment of myocardial infarction (MI) remains a substantial challenge due to excessive inflammation, massive cell death, and restricted regenerative potential, leading to maladaptive healing process and eventually heart failure. Current strategies of regulating inflammation or improving cardiac tissue regeneration have limited success. Herein, a hybrid hydrogel coassembled by acellular cardiac extracellular matrix (ECM) and immunomodulatory glycopeptide is developed for endogenous tissue regeneration after MI. The hydrogel constructs a niche recapitulating the architecture of native ECM for attracting host cell homing, controlling macrophage differentiation via glycopeptide unit, and promoting endotheliocyte proliferation by enhancing the macrophage‐endotheliocyte crosstalk, which coordinate the innate healing mechanism for cardiac tissue regeneration. In a rodent MI model, the hybrid hydrogel successfully orchestrates a proreparative response indicated by enhanced M2 macrophage polarization, increased angiogenesis, and improved cardiomyocyte survival, which alleviates infarct size, improves wall thicknesses, and enhances cardiac contractility. Furthermore, the safety and effectiveness of the hydrogel are demonstrated in a porcine MI model, wherein proteomics verifies the regulation of immune response, proangiogenesis, and accelerated healing process. Collectively, the injectable composite hydrogel serving as an immunomodulatory niche for promoting cell homing and proliferation, inflammation modulation, tissue remodeling, and function restoration provides an effective strategy for endogenous cardiac repair.

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

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.

Background: Transcatheter edge-to-edge repair (TEER) of the mitral valve has emerged as an alternative treatment for mitral regurgitation (MR). However, the high radiation exposure during the process has been associated with multiple adverse effects for medical staff. In this study, we assessed the feasibility and safety of TEER performed solely under the echocardiographic (echo) guidance. Methods: Between April 2021 to August 2021, we retrospectively collected characteristics of 23 patients with MR who underwent TEER under echocardiographic guidance exclusively. Follow-up evaluations were performed at 1- , 3-months and 1-year post procedure. Results: All 23 patients (mean age, 66.1 ± 12.1 years; 65.2% males) successfully underwent echo-guided TEER, with 22 patients under transesophageal echo (TEE) guidance and 1 patient under transthoracic echo (TTE) guidance for severe esophageal stenosis. Of the patients, 60.9% received 1 implant and 39.1% received 2 implants. The median total procedural time was 130 (interquartile range, IQR: 90–150) min and the device procedure time was 73 (IQR: 58–100) min. The median length of stay was 6 (IQR: 5–9) days. At 3-months follow-up, 63.6% of patients had an MR ≤1+ and 90.9% had an MR ≤2+ (p < 0.001 vs. baseline). Improvement in functional status was observed, with 40.9% of patients classified as New York Heart Association (NYHA) functional class I and 45.5% as NYHA functional class II (p < 0.001 compared to baseline) at 3-months. At 1-year follow-up, 90.4% maintained MR reduction with MR ≤2+ (p < 0.001 vs. baseline). Single leaflet device attachment (SLDA) occurred in one patient (4.3%) 1-week post procedure. Conclusions: This retrospective, single-center, and pilot study demonstrates the feasibility, safety, and low complication rates of TEER guided solely by echocardiography. Our findings support the systematic use of echocardiography as the sole guidance modality for TEER, highlighting its potential as an alternative to fluoroscopy-guided procedures. Further multicenter and comparative studies are warranted to confirm these results and provide a more comprehensive evaluation of this approach.

Herbicides are the agents of choice for use in weed control; however, they can enter the aquatic environment, with potentially serious consequences for non-target organisms. Despite the possible deleterious effects, little information is available regarding the ecotoxicity of the herbicide florasulam toward aquatic organisms. Accordingly, in this study, we investigated the toxic effect of florasulam on the freshwater microalga Chlorella vulgaris and sought to identify the underlying mechanisms. For this, we employed a growth inhibition toxicity test, and then assessed the changes in physiological and metabolomic parameters, including photosynthetic pigment content, antioxidant system, intracellular structure and complexity, and metabolite levels. The results showed that treatment with florasulam for 96 h at the concentration of 2 mg/L, 2.84 mg/L, and 6 mg/L in medium significantly inhibited algal growth and photosynthetic pigment content. Moreover, the levels of reactive oxygen species were also increased, resulting in oxidative damage and the upregulation of the activities of several antioxidant enzymes. Transmission electron microscopic and flow cytometric analysis further demonstrated that exposure to florasulam (6 mg/L) for 96 h disrupted the cell structure of C. vulgaris, characterized by the loss of cell membrane integrity and alterations in cell morphology. Changes in amino acid metabolism, carbohydrate metabolism, and the antioxidant system were also observed and contributed to the suppressive effect of florasulam on the growth of this microalga. Our findings regarding the potential risks of florasulam in aquatic ecosystems provide a reference for the safe application of this herbicide in the environment.

BackgroundChronic calcium channel blockers (CCBs) are indicated in children with idiopathic/heritable pulmonary arterial hypertension (IPAH/HPAH) and positive response to acute vasodilator challenge. However, minimal safety data are available on the long-term high-dose exposure to CCBs in this population.MethodsPatients aged 3 months to 18 years who were diagnosed with IPAH/HPAH and treated with CCB in the past 15 years were retrospectively reviewed. The maximum tolerated dose and the long-term safety of high-dose CCBs on the cardiovascular and noncardiovascular systems were assessed.ResultsThirty-two eligible children were enrolled in the study, with a median age of 9 (6–11) years old. Thirty-one patients were treated with diltiazem after diagnosis. The median maximum tolerated dose was 12.9 (9.8–16.8) mg/kg/day. Children younger than 7 years used higher doses than children in the older age group, 16.4 (10.5–28.5) mg/kg/day vs. 12.7 (6.6–14.4) mg/kg/day, P < 0.05. Patients were followed up for a median period of 6.2 (2.6–10.8) years. One patient died from a traffic accident, and others showed a stable or improved WHO functional class status. Thirteen (40.6%) and 10 (31.3%) patients developed arrhythmias and hypotension. Nine (28.1%) patients had sinus bradycardia, five (21.9%) had first-degree or second-degree type II atrial-ventricular blocks, and two (6.3%) had second-degree type II atrial-ventricular blocks. Most of these arrhythmias were transient and relieved after CCB dose adjustment. The most reported noncardiovascular adverse effect was gingival hyperplasia (13, 40.6%), accompanied by different degrees of dental dysplasia. No liver or kidney dysfunction was reported.ConclusionDiltiazem was used in a very high dose for eligible children with IPAH/HPAH. The toxicity of long-term CCB use on the cardiovascular system is mild and controllable. Clinicians should also monitor the noncardiovascular adverse effects associated with drug therapy.

ABSTRACT Global population immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accumulating through heterogeneous combinations of infection and vaccination. Vaccine distribution in low- and middle-income countries has been variable and reliant on diverse vaccine platforms. We studied B-cell immunity in Mexico, a middle-income country where five different vaccines have been deployed to populations with high SARS-CoV-2 incidences. Levels of antibodies that bound a stabilized prefusion spike trimer, neutralizing antibody titers, and memory B-cell expansion correlated with each other across vaccine platforms. Nevertheless, the vaccines elicited variable levels of B-cell immunity, and the majority of recipients had undetectable neutralizing activity against the recently emergent omicron variant. SARS-CoV-2 infection, experienced before or after vaccination, potentiated B-cell immune responses and enabled the generation of neutralizing activity against omicron and SARS-CoV for all vaccines in nearly all individuals. These findings suggest that broad population immunity to SARS-CoV-2 will eventually be achieved but by heterogeneous paths. IMPORTANCE The majority of studies on SARS-CoV-2 vaccine-elicited immunity and immune evasion have focused on single vaccines corresponding to those distributed in high-income countries. However, in low- and middle-income countries, vaccine deployment has been far less uniform. It is therefore important to determine the levels of immunity elicited by vaccines that have been deployed globally. Such data should help inform policy. Thus, this paper is very much a “real-world” study that focuses on a middle-income country, Mexico, in which five different vaccines based on mRNA, adenovirus, and inactivated-virus platforms have been extensively deployed, while (as documented in our study) SARS-CoV-2 variants with increasing degrees of immune evasiveness have propagated in the Mexican population, culminating in the recent emergence of B.1.1.529 (omicron).

Abstract QYM201, 1-(2-chloro-3-(3-cyclopropyl-5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-6-(trifluoromethyl)phenyl)piperidin-2-one), is a newly developed HPPD- (4-hydroxyphenylpyruvate dioxygenase; EC 1.13.11.27) inhibiting herbicide for weed control. Experiments were carried out to determine the effect of QYM201 on weeds and its safety for wheat in the glasshouse and field. The results indicated that at doses of 90 and 135 g active ingredient (a.i.) ha−1 QYM201 was highly effective against both grass and broadleaf weeds, such as Alopecurus aequalis Sobol., Alopecurus japonicus Steud, and Capsella bursa-pastoris Medic. In a wheat hybrid tolerance experiment, QYM201 showed a high level of safety for most of the 17 tested wheat hybrids, and the SI values reached ≥5.7 in the selectivity index study. To determine application rules for QYM201, field experiments were conducted in 2016 and 2017. During this time, 90 to 270 g a.i. ha−1 post-emergence herbicide application (POST) was sufficient to supply satisfactory all-season control of Alopecurus aequalis Sobol., Descurainia sophia [L.] Schur., and Malachium aquaticum (L.) Fires. No damage to wheat plants was observed. In order to increase wheat yield and deliver effective weed control, a dosage of 90 to 180 g a.i. ha−1 is suggested. In conclusion, the herbicide QYM201 is safe to use in wheat fields to control winter weeds.

Pesticides can affect non-target microorganisms in the soil and are directly related to soil microecological health and environmental safety. Oxathiapiprolin is a piperidinyl thiazole isoxazoline fungicide that shows excellent control effect against oomycete fungal diseases, including late blight, downy mildew, root rot, stem rot, and blight. Though it can exist stably in the soil for a long time, its effects on soil microbial structure and diversity are not well investigated. In the present study, the effects of oxathiapiprolin on the abundance and diversity of soil fungal communities in typical farmland were studied. The results show that the abundance and diversity of soil fungi were increased by oxathiapiprolin treatment with differences not significant on the 30th day. Oxathiapiprolin was found to change the structure of soil fungal communities, among which Ascomycota and Mortierellomycota were the most affected. Undefined saprophytic fungi increased in the treatment groups, and the colonization of saprophytic fungi can act as a major contributor to the function of soil microbial communities. This study lays a solid foundation regarding environmental behavior with the use of oxathiapiprolin in soil and details its scientific and rational use.

Cyantraniliprole is a novel diamide insecticide that acts upon the ryanodine receptor (RyR) and has broad application prospects. Accordingly, it is very important to evaluate the toxicity of cyantraniliprole to earthworms (Eisenia fetida) because of their vital role in maintaining a healthy soil ecosystem. In this study, an experiment was set up, using four concentrations (0.1, 1, 5, and 10 mg/kg) and solvent control group (0 mg/kg), to investigate the ecotoxicity of cyantraniliprole to earthworms. Our results showed that, after 28 days of exposure to cyantraniliprole, both cocoon production and the number of juvenile earthworms had decreased significantly at concentrations of either 5 or 10 mg/kg. On day 14, we measured the activities of digestive enzymes and ion pumps in the intestinal tissues of earthworms. These results revealed that cyantraniliprole exposure caused intestinal damage in earthworm, specifically changes to its intestinal enzyme activity and calcium ion content. Cyantraniliprole could lead to proteins’ carbonylation under the high-dose treatments (i.e., 5 mg/kg, 10 mg/kg). At the same time, we also found that cyantraniliprole can cause the abnormal expression of key functional genes (including HSP70, CAT, RYR, ANN, and CAM genes). Moreover, the transcriptomics data showed that exposure to cyantraniliprole would affect the synthesis of carbohydrates, proteins and lipids, as well as their absorption and transformation, while cyantraniliprole would also affect signal transduction. In general, high-dose exposure to cyantraniliprole causes reproductive toxicity, genotoxicity, and intestinal damage to earthworms.

Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor-binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.

The HIV-1 Vpr accessory protein induces ubiquitin/proteasome-dependent degradation of many cellular proteins by recruiting them to a cullin4A-DDB1-DCAF1 complex. In so doing, Vpr enhances HIV-1 gene expression and induces (G2/M) cell cycle arrest. However, the identities of Vpr target proteins through which these biological effects are exerted are unknown. We show that a chromosome periphery protein, CCDC137/cPERP-B, is targeted for depletion by HIV-1 Vpr, in a cullin4A-DDB1-DCAF1 dependent manner. CCDC137 depletion caused G2/M cellcycle arrest, while Vpr-resistant CCDC137 mutants conferred resistance to Vpr-induced G2/M arrest. CCDC137 depletion also recapitulated the ability of Vpr to enhance HIV-1 gene expression, particularly in macrophages. Our findings indicate that Vpr promotes cell-cycle arrest and HIV-1 gene expression through depletion of CCDC137.

Background. Percutaneous occlusion under fluoroscopy guidance has become the preferred method for the treatment of patent ductus arteriosus (PDA). To avoid radiation exposure and contrast agent use, PDA occlusion under transthoracic echocardiography (TTE) guidance was conducted. Objectives. We assessed the hypothesis that the success rate of percutaneous PDA occlusion under TTE was noninferior to that under fluoroscopy guidance. Methods. In this single-center trial, 100 patients were randomly assigned in a 1 : 1 ratio to the TTE group (n = 50) or to the fluoroscopy group (n = 50). The primary endpoint was the success rate of occlusion, with the noninferiority margin set at 8% for the between-group difference in intention-to-treat analysis. Secondary endpoints were hospitalization duration, cost, procedure time, and rate of adverse events including occluder migration, hemolysis, peripheral vascular complications, and residual shunt at 1-month and 12-month follow-up. Results. Patient, defect, and device characteristics were similarly distributed between groups. The success rate of occlusion was 98% for the TTE group and 100% for the fluoroscopy group (absolute difference: −2%; 95% confidence interval: −5.9% to 1.9%). Cost and procedure duration were significantly lower in the TTE group, without adverse events in either group at a median of 12.0 months (range, 10.0–15.5 months) of follow-up. Conclusion. Percutaneous PDA occlusion can be performed via TTE guidance safely and effectively, and the success rate of the TTE-guided procedure was noninferior to that under fluoroscopy guidance, with reduced cost and procedure time. The trial is registered with http://www.chictr.org.cn (ChiCTR-ICR-15006334).

The dynamics of the late stages of the HIV-1 life cycle are poorly documented. Viral replication dynamics are typically measured in populations of infected cells, but asynchrony that is introduced during the early steps of HIV-1 replication complicates the measurement of the progression of subsequent steps and can mask replication dynamics and their variation in individual infected cells. We established microscopy-based methods to dynamically measure HIV-1-encoded reporter gene and antiviral gene expression in individual infected cells. We coupled these measurements with conventional analyses to quantify delays in the HIV-1 replication cycle imposed by the biphasic nature of HIV-1 gene expression and by the assembly-inhibiting property of the matrix domain of Gag. We further related the dynamics of restriction factor (APOBEC3G) removal to the dynamics of HIV-1 replication in individual cells. These studies provide a timeline for key events in the HIV-1 replication cycle, and reveal that the interval between the onset of early and late HIV-1 gene expression is only ~3 h, but matrix causes a ~6-12 h delay in the generation of extracellular virions. Interestingly, matrix delays particle assembly to a time at which APOBEC3G has largely been removed from the cell. Thus, a need to prepare infected cells to be efficient producers of infectious HIV-1 may provide an impetus for programmed delays in HIV-1 virion genesis. Our findings also emphasize the significant heterogeneity in the length of the HIV-1 replication cycle in homogenous cell populations and suggest that a typical infected cell generates new virions for only a few hours at the end of a 48 h lifespan. Therefore, small changes in the lifespan of infected cells might have a large effect on viral yield in a single cycle and the overall clinical course in infected individuals.

Elastic modulus is an important physical parameter of molding sand; it is closely connected with molding sand's properties. Based on theories of rheology and molding sand microdeformation, elastic modulus of molding sand was measured and investigated using the intelligent molding sand multi-property tester developed by ourselves. The measuring principle was introduced. Effects of bentonite percentage and compactibility of the molding sand were experimentally studied. Furthermore, the essential viscoelastic nature of green sand was analyzed. It is considered that viscoelastic deformation of molding sand consists mainly of that of Kelvin Body of clay membrane, and elastic modulus of molding sand depends mainly on that of Kelvin Body which is the elastic component of clay membrane between sands. Elastic modulus can be adopted as one of the property parameters, and can be employed to evaluate viscoelastic properties of molding sand.

The morphogenesis of retroviral particles is driven by Gag and GagPol proteins that provide the major structural component and enzymatic activities required for particle assembly and maturation. In addition, a number of cellular proteins are found in retrovirus particles; some of these are important for viral replication, but many lack a known functional role. One such protein is clathrin, which is assumed to be passively incorporated into virions due to its abundance at the plasma membrane. We found that clathrin is not only exceptionally abundant in highly purified HIV-1 particles but is recruited with high specificity. In particular, the HIV-1 Pol protein was absolutely required for clathrin incorporation and point mutations in reverse transcriptase or integrase domains of Pol could abolish incorporation. Clathrin was also specifically incorporated into other retrovirus particles, including members of the lentivirus (simian immunodeficiency virus, SIVmac), gammaretrovirus (murine leukemia virus, MLV) and betaretrovirus (Mason-Pfizer monkey virus, M-PMV) genera. However, unlike HIV-1, these other retroviruses recruited clathrin primarily using peptide motifs in their respective Gag proteins that mimicked motifs found in cellular clathrin adaptors. Perturbation of clathrin incorporation into these retroviruses, via mutagenesis of viral proteins, siRNA based clathrin depletion or adaptor protein (AP180) induced clathrin sequestration, had a range of effects on the accuracy of particle morphogenesis. These effects varied according to which retrovirus was examined, and included Gag and/or Pol protein destabilization, inhibition of particle assembly and reduction in virion infectivity. For each retrovirus examined, clathrin incorporation appeared to be important for optimal replication. These data indicate that a number of retroviruses employ clathrin to facilitate the accurate morphogenesis of infectious particles. We propose a model in which clathrin contributes to the spatial organization of Gag and Pol proteins, and thereby regulates proteolytic processing of virion components during particle assembly.

Lentiviral Nef proteins have multiple functions and are important for viral pathogenesis. Recently, Nef proteins from many simian immunodefiency viruses were shown to antagonize a cellular antiviral protein, named Tetherin, that blocks release of viral particles from the cell surface. However, the mechanism by which Nef antagonizes Tetherin is unknown. Here, using related Nef proteins that differ in their ability to antagonize Tetherin, we identify three amino-acids in the C-terminal domain of Nef that are critical specifically for its ability to antagonize Tetherin. Additionally, divergent Nef proteins bind to the AP-2 clathrin adaptor complex, and we show that residues important for this interaction are required for Tetherin antagonism, downregulation of Tetherin from the cell surface and removal of Tetherin from sites of particle assembly. Accordingly, depletion of AP-2 using RNA interference impairs the ability of Nef to antagonize Tetherin, demonstrating that AP-2 recruitment is required for Nef proteins to counteract this antiviral protein.