A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2.

An outbreak of coronavirus disease 2019 (COVID-19)1-3, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)4, has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.

Polymorphospora lycopeni sp. nov., a lycopene-producing actinomycetes isolated from lakeside soil sample of Baiyangdian.

A novel actinomycetes producing lycopene, designated HBU208002T, was isolated from a lakeside soil sample collected in Baiyangdian, located in Xiong'an New Area of China, and its taxonomic position was investigated by a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that the strain HBU208002T fell within the genus Polymorphospora and was closely related to Polymorphospora rubra JCM 14904T (99.73% identity). However, the average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH) and average amino acid identity (AAI) values between the strain HBU208002T and P. rubra JCM 14904T were 91.78, 44.7 and 91.6%, respectively, which were lower than the ANI (95-96%), DDH (>70%) and AAI (>95%) thresholds of prokaryotic microbial defined species. The predominant fatty acids of the strain HBU208002T were iso-C16:0, C17:1 ω8c. The menaquinones of the strain HBU208002T were MK-8(H8) and MK9(H4), while those of P. rubra JCM 14904T were MK-10(H6), MK-10(H4), MK-9(H6) and MK-9(H4). Meanwhile, some phenotypic characterizations and antibacterial activities distinguished the strain HBU208002T from P. rubra JCM 14904T. The strain HBU208002T exhibited inhibitory effects on Fusarium graminearum, Fusarium verticillioides and Botrytis cinerea, but P. rubra JCM 14904T had no activity. Therefore, the strain HBU208002T should be assigned as representing a novel species of the genus Polymorphospora, for which the name Polymorphospora lycopeni was proposed. The type strain is HBU208002T (=KCTC49833T = GDMCC4.236T).

Left atrial appendage aneurysm in pediatrics.

Left atrial appendage aneurysm (LAAA) is a rare cardiac anomaly with potentially life-threatening complications of atrial tachyarrhythmias and systemic thromboembolism. It is often diagnosed incidentally and rarely during childhood. Echocardiography is considered the primary method of LAAA diagnosis; in particular, the subxiphoid view is more useful in pediatrics. Surgical intervention and drug management are recommended to prevent potentially lethal complications. Herein, we report five cases of patients with LAAA during infancy and childhood, caused by both congenital and acquired conditions. One patient underwent surgical resection through left lateral thoracotomy without cardiopulmonary bypass and another patient underwent drug management.

Diagnosis of double-chambered left ventricle using echocardiography.

Double-chambered left ventricle (DCLV) is a particularly rare congenital cardiovascular malformation that is difficult to diagnose. It is characterized by the subdivision of the left ventricle into two chambers by an abnormal septum or muscle band. Here, we report 12 patients with DCLV. Differential diagnoses of DCLV include four other cardiac diseases, diverticulum, aneurysm, hypertrophic cardiomyopathy, and left ventricular noncompaction. Echocardiography plays an important role in the diagnosis of this rare condition and in differentiating it from other diseases.

A Matrix Information-Geometric Method for Change-Point Detection of Rigid Body Motion.

A matrix information-geometric method was developed to detect the change-points of rigid body motions. Note that the set of all rigid body motions is the special Euclidean group S E ( 3 ) , so the Riemannian mean based on the Lie group structures of S E ( 3 ) reflects the characteristics of change-points. Once a change-point occurs, the distance between the current point and the Riemannian mean of its neighbor points should be a local maximum. A gradient descent algorithm is proposed to calculate the Riemannian mean. Using the Baker-Campbell-Hausdorff formula, the first-order approximation of the Riemannian mean is taken as the initial value of the iterative procedure. The performance of our method was evaluated by numerical examples and manipulator experiments.

Application of a full model-based iterative reconstruction (MBIR) in 80 kVp ultra-low-dose paranasal sinus CT imaging of pediatric patients.

OBJECTIVE: To evaluate the clinical application of a full model-based iterative reconstruction (MBIR) algorithm in the ultra-low-dose paranasal sinus CT imaging of children. MATERIALS AND METHODS: In the first phase, 16 low-dose CT dacryocystography (DCG) (80 kV/64 mAs) scans were reconstructed with MBIR and filtered back-projection (FBP) to demonstrate noise reduction capability of MBIR. MBIR images were also compared with the images of 21 standard-dose paranasal sinus patients reconstructed with adaptive statistical iterative reconstruction (ASIR) algorithm. In the second phase, 14 pediatric tumors patients (images with ASIR in the initial scan) who came for follow-up paranasal sinus CT scan were prospectively enrolled with reduced radiation and MBIR algorithm. In both study phases, image noise and the contrast noise ratio (CNR) of sphenoid was measured; and subjective image quality was evaluated. CTDIvol and DLP were recorded, and effective dose calculated. RESULTS: The CTDIvol value for the DCG group was 63.9% lower than the standard-dose sinus group (1.09 ± 0.01 mGy vs. 3.02 ± 0.35 mGy). Compared with the ASIR reconstruction in the standard-dose sinus patient group, images with MBIR in the ultra-low-dose DCG group had 39.9% lower noise (9.5 ± 0.8HU vs. 15.8 ± 3.3HU) and 63.6% higher CNR (14.4 ± 4.7 vs. 8.8 ± 2.2), with similar subjective image quality score. For the tumor patients, 65.5% dose reduction was achieved. Subjective quality scores were similar between the initial and follow-up scans. Objective noise was significantly lower for the follow-up group. CONCLUSION: MBIR provided equal or better image quality with significantly reduced radiation dose in paranasal sinus CT imaging of pediatric patients compared with standard-dose CT with ASIR algorithm.

Image quality improvement using model-based iterative reconstruction in low dose chest CT for children with necrotizing pneumonia.

BACKGROUND: Model-based iterative reconstruction (MBIR) is a promising reconstruction method which could improve CT image quality with low radiation dose. The purpose of this study was to demonstrate the advantage of using MBIR for noise reduction and image quality improvement in low dose chest CT for children with necrotizing pneumonia, over the adaptive statistical iterative reconstruction (ASIR) and conventional filtered back-projection (FBP) technique. METHODS: Twenty-six children with necrotizing pneumonia (aged 2 months to 11 years) who underwent standard of care low dose CT scans were included. Thinner-slice (0.625 mm) images were retrospectively reconstructed using MBIR, ASIR and conventional FBP techniques. Image noise and signal-to-noise ratio (SNR) for these thin-slice images were measured and statistically analyzed using ANOVA. Two radiologists independently analyzed the image quality for detecting necrotic lesions, and results were compared using a Friedman's test. RESULTS: Radiation dose for the overall patient population was 0.59 mSv. There was a significant improvement in the high-density and low-contrast resolution of the MBIR reconstruction resulting in more detection and better identification of necrotic lesions (38 lesions in 0.625 mm MBIR images vs. 29 lesions in 0.625 mm FBP images). The subjective display scores (mean ± standard deviation) for the detection of necrotic lesions were 5.0 ± 0.0, 2.8 ± 0.4 and 2.5 ± 0.5 with MBIR, ASIR and FBP reconstruction, respectively, and the respective objective image noise was 13.9 ± 4.0HU, 24.9 ± 6.6HU and 33.8 ± 8.7HU. The image noise decreased by 58.9 and 26.3% in MBIR images as compared to FBP and ASIR images. Additionally, the SNR of MBIR images was significantly higher than FBP images and ASIR images. CONCLUSIONS: The quality of chest CT images obtained by MBIR in children with necrotizing pneumonia was significantly improved by the MBIR technique as compared to the ASIR and FBP reconstruction, to provide a more confident and accurate diagnosis for necrotizing pneumonia.

Effectiveness of ultrasound-guided percutaneous microwave ablation for symptomatic uterine fibroids: a multicentre study in China.

PURPOSE: To evaluate the clinical efficacy of ultrasound-guided percutaneous microwave ablation (PMWA) therapy for symptomatic uterine fibroids in a multicentre study. MATERIALS AND METHODS: Patients with symptomatic uterine fibroids who underwent PMWA at multiple treatment centres in China between January 2013 and August 2015 were prospectively studied to compare the reduction rate of uterine fibroids, haemoglobin level and uterine fibroid symptom and health-related quality of life questionnaire (UFS-QOL) scores before and at 3, 6 and 12 months after ablation. RESULTS: A total of 311 patients (405 leiomyomas) from eight treatment centres underwent the treatment (age, 29-55 years; mean ± SD, 41 ± 5.11 years). The mean diameter of the myomas ranged from 2.03 to 12.50 cm (mean, 5.10 ± 1.28 cm) and the volume ranged from 4.40 to 1022.14 cm3 (mean, 95.01 ± 70.29 cm3). Forty-eight myomas were identified as FIGO type 1/2 fibroids, 256 as type 3/4 fibroids and 101 as type 5/6 fibroids. The mean ablation rate was 86.6% (54.0-100%). The mean reduction rate was 63.5%, 78.5% and 86.7% at 3, 6 and 12 months posttreatment, respectively. The haemoglobin level increased significantly from 88.84 ± 9.31 g/L before treatment to 107.14 ± 13.32, 116.05 ± 7.66 and 117.79 ± 6.51 g/L at 3, 6 and 12 months posttreatment, respectively (p = .000). The symptom severity score (SSS) and health-related quality of life (HRQL) scores were also significantly improved posttreatment compared with before treatment (p = .000). CONCLUSION: PMWA is an effective, minimally invasive treatment for symptomatic leiomyomas that can significantly improve the quality of life of patients.

Anomalous origin of the left coronary artery from the pulmonary artery in infants: imaging findings and clinical implications of cardiac computed tomography.

PURPOSE: This study aimed to retrospectively analyze the imaging features of an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) in pediatric patients, with cardiac computed tomography (CT) and echocardiography. MATERIALS AND METHODS: To define the precise location of ostium of the left coronary artery, we examined 9 patients using chest film, electrocardiogram, echocardiography, and cardiac CT 4 modalities, 2 of them also using cardiac MR and 1 of them using catheter cardiac angiography. Cardiac CT scan was performed in all 9 patients using a body size adapted low-dose protocol after bolus injection of intravenous nonionic contrast medium. Multiplane reconstruction, maximum intensity projection, and 3-dimensional coronary tree images were obtained for each patient. Two radiologists in consensus analyzed the cardiac CT findings for the origin of the anomalous coronary artery, course, and collateral vessels. The ALCAPA in these 9 patients was confirmed retrospectively by surgery. RESULTS: Cardiac CT can distinguish the site of origin of the anomalous left coronary artery and variants: 2 patients with inner ostium of the pulmonary trunk, 3 patients with left-sided ostium, 2 patients with posterior ostium, and 2 patients with sinus of the pulmonary root ostium; 1 patient combined with the right coronary artery arising from the left coronary sinus. CONCLUSIONS: Cardiac CT can provide fast and accurate depiction of complex coronary arteries, particularly in unstable and fragile patients with ALCAPA, and according to cardiac CT, surgical strategies can be decided.

Improving pulmonary vessel image quality with a full model-based iterative reconstruction algorithm in 80kVp low-dose chest CT for pediatric patients aged 0-6 years.

BACKGROUND: Full model-based iterative reconstruction (MBIR) algorithm decreasing image noise and improving spatial resolution significantly, combined with low voltage scan may improve image and vessels quality. PURPOSE: To evaluate the image quality improvement of pulmonary vessels using a full MBIR in low-dose chest computed tomography (CT) for children. MATERIAL AND METHODS: This study was institutional review board approved. Forty-one children (age range, 28 days-6 years, mean age, 2.0 years) who underwent 80 kVp low-dose CT scans were included. Age-dependent noise index (NI) for a 5-mm slice thickness image was used for the acquisition: NI = 11 for 0-12 months old, NI = 13 for 1-2 years old, and NI = 15 for 3-6 years old. Images were retrospectively reconstructed into thin slice thickness of 0.625 mm using the MBIR and a conventional filtered back projection (FBP) algorithm. Two radiologists independently evaluated images subjectively focusing on the ability to display small arteries and diagnosis confidence on a 5-point scale with 3 being clinically acceptable. CT value and image noise in the descending aorta, muscle and fat were measured and statistically compared between the two reconstruction groups. RESULTS: The ability to display small vessels was significantly improved with the MBIR reconstruction. The subjective scores of displaying small vessels were 5.0 and 3.7 with MBIR and FBP, respectively, while the respective diagnosis confidence scores were 5.0 and 3.8. Quantitative image noise for the 0.625 mm slice thickness images in the descending aorta was 15.8 ± 3.8 HU in MBIR group, 57.3% lower than the 37.0 ± 7.3 HU in FBP group. The signal-to-noise ratio and contrast-to-noise ratio for the descending aorta were 28.3 ± 7.9 and 24.05 ± 7.5 in MBIR group, and 12.1 ± 3.7 and 10.6 ± 3.5 in FBP group, respectively. These values were improved by 133.9% and 132.1%, respectively, with MBIR reconstruction compared to FBP reconstruction. CONCLUSION: Compared to the conventional FBP reconstruction, the image quality and diagnostic performance for pulmonary vessels was significantly improved by the MBIR reconstruction in low-dose chest CT in children.

Based on Sportomics: Comparison of Physiological Status of Collegiate Sprinters in Different Pre-Competition Preparation Periods.

This study aimed to assess the impact of pre-competition training by comparing the differences of collegiate sprinters in physiological state between strengthening and tapering training period by sportomics and combining their sport performance. Fifteen collegiate sprinters were investigated or tested on their body composition, dietary habits, energy expenditure, sleep efficiency, heart rate and respiratory rate during training, blood (blood cells, biochemical and immune markers) and urine (urinalysis), gut microbiome distribution, microbiome and blood metabolites, and their functions during the strengthening (Group A) and tapering training period (Group B) prior to competing in the national competitions. We found that 26.67% of sprinters achieved personal bests (PB) after the competition. The limb skeletal muscle mass and lymphocyte ratio of male sprinters in Group B were lower than those in Group A, and the serum creatine kinase (CK) level was higher than Group A (p < 0.05). The levels of serum CK, interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and urine-specific gravity (SG) of the two groups were higher than the upper limit of the reference value. The detection rates of urine white blood cell (WBC) and protein in Group B were higher than those in Group A. The gut microbiome health index (GMHI) of Group A was higher than that of Group B, and the microbial dysbiosis index was lower than that of Group B. The ratio of Firmicutes/Bacteroidota (F/B) in Group A was higher than that in Group B. There were 65 differential metabolites in the A/B group, and the enriched pathway was mainly the NF-kappa B signaling pathway (up); B/T cell receptor signaling pathway (up); Th1 and Th2 cell differentiation (up); phenylalanine metabolism (up); and growth hormone synthesis, secretion, and action (up). There were significant differences in blood metabolites between the A and B groups, with a total of 89 differential metabolites, and the enriched pathway was mainly the NF-kappa B signaling pathway (up), T cell receptor signaling pathway (up), Th1 and Th2 cell differentiation (up), and glycerophospholipid metabolism (down). In conclusion, the imbalance of the gut microbiome and inflammation and immune-related metabolites of collegiate sprinters during the pre-competition tapering training period may be the cause of their limited sports performance.

Microbial diversity and their extracellular enzyme activities among different soil particle sizes in mossy biocrust under N limitation in the southeastern Tengger Desert, China.

Introduction: Mossy biocrust represents a stable stage in the succession of biological soil crust in arid and semi-arid areas, providing a microhabitat that maintains microbial diversity. However, the impact of mossy biocrust rhizoid soil and different particle sizes within the mossy biocrust layer and sublayer on microbial diversity and soil enzyme activities remains unclear. Methods: This study utilized Illumina MiSeq sequencing and high-throughput fluorometric technique to assess the differences in microbial diversity and soil extracellular enzymes between mossy biocrust rhizoid soil and different particle sizes within the mossy biocrust sifting and sublayer soil. Results: The results revealed that the total organic carbon (TOC), total nitrogen (TN), ammonium (NH4+) and nitrate (NO3-) in mossy biocrust rhizoid soil were the highest, with significantly higher TOC, TN, and total phosphorus (TP) in mossy biocrust sifting soil than those in mossy biocrust sublayer soil. Extracellular enzyme activities (EAAs) exhibited different responses to various soil particle sizes in mossy biocrust. Biocrust rhizoid soil (BRS) showed higher C-degrading enzyme activity and lower P-degrading enzyme activity, leading to a significant increase in enzyme C: P and N: P ratios. Mossy biocrust soils were all limited by microbial relative nitrogen while pronounced relative nitrogen limitation and microbial maximum relative carbon limitation in BRS. The diversity and richness of the bacterial community in the 0.2 mm mossy biocrust soil (BSS0.2) were notably lower than those in mossy biocrust sublayer, whereas the diversity and richness of the fungal community in the rhizoid soil were significantly higher than those in mossy biocrust sublayer. The predominant bacterial phyla in mossy biocrust were Actinobacteriota, Protebacteria, Chloroflexi, and Acidobacteriota, whereas in BSS0.2, the predominant bacterial phyla were Actinobacteriota, Protebacteria, and Cyanobacteria. Ascomycota and Basidiomycota were dominant phyla in mossy biocrust. The bacterial and fungal community species composition exhibited significant differences. The mean proportions of Actinobacteriota, Protebacteria, Chloroflexi, Acidobacteriota, Acidobacteria, Cyanobacteria, and Bacteroidota varied significantly between mossy biocrust rhizoid and different particle sizes of mossy biocrust sifting and sublayer soil (p < 0.05). Similarly, significant differences (p < 0.05) were observed in the mean proportions of Ascomycota, Basidiomycota, and Glomeromycota between mossy biocrust rhizoid and different particle sizes within the mossy biocrust sifting and sublayer soil. The complexity and connectivity of bacterial and fungal networks were higher in mossy biocrust rhizoid soil compared with different particle sizes within the mossy biocrust sifting and sublayer soil. Discussion: These results offer valuable insights to enhance our understanding of the involvement of mossy biocrust in the biogeochemical cycle of desert ecosystems.

Riemannian means on special euclidean group and unipotent matrices group.

Among the noncompact matrix Lie groups, the special Euclidean group and the unipotent matrix group play important roles in both theoretic and applied studies. The Riemannian means of a finite set of the given points on the two matrix groups are investigated, respectively. Based on the left invariant metric on the matrix Lie groups, the geodesic between any two points is gotten. And the sum of the geodesic distances is taken as the cost function, whose minimizer is the Riemannian mean. Moreover, a Riemannian gradient algorithm for computing the Riemannian mean on the special Euclidean group and an iterative formula for that on the unipotent matrix group are proposed, respectively. Finally, several numerical simulations in the 3-dimensional case are given to illustrate our results.

Effective long-term sirolimus treatment in hypoxemia mainly due to intrapulmonary right-to-left shunt in a patient with multiple vascular anomalies.

Pulmonary arteriovenous malformations (PAVMs), particularly where feeding artery/arteries to PAVMs ≥ 3 mm can be treated with embolization. The treatment for hypoxemia resulting from multiple small or diffuse PAVMs remains unclear.We report a girl aged 5 years and 10 months presented with cyanosis and decreased activity after exercise (83-85% of pulse oxygen saturation, SpO2). She had 1 skin lesion on her face and 1 suspected hemangioma on her left upper extremity at birth and that gradually disappeared spontaneously. Physical examination revealed clubbed fingers, and abundant vascular networks on her back. Contrast-enhanced lung CT (slice thickness:1.25 mm) with vascular three-dimensional reconstruction and abdominal CT revealed increased bronchovascular bundles, increased diameter of the pulmonary artery and ascending aorta, and intrahepatic portosystemic venous shunts due to patent ductus venosus. Echocardiography revealed increased diameter of aortic and pulmonary artery. Transthoracic contrast echocardiography was highly positive (bubble appearing in the left ventricle after 5 cardiac cycles). Abdominal doppler ultrasound revealed hepatic-portal venous shunt. Magnetic resonance imaging, artery and vein of the brain revealed multiple malformations of venous sinuses. The patient received sirolimus for 2 years and 4 months. Her condition improved significantly. SpO2 gradually increased to 98%. Her finger clubbing gradually normalized.Our report implicates sirolimus might be a potential treatment option in persistent hypoxemia mainly due to intrapulmonary right-to-left shunt even small multiple or diffusive PAVMs in pediatric patients with multiple cutaneous and visceral vascular anomalies.

Convex and Concave Model 3D Printing for Designing Right-side Bronchial Blocker for Infants.

It is technically challenging for pediatric anesthesiologists to use bronchial blocker (BB) to isolate the lungs of infants during thoracoscopic surgery. Further, BB currently sold in the market cannot match the anatomical characteristics of the infants, especially on the right main bronchus. It may easily cause poor exhaustion of the right upper lobe, which leads to interference with the thoracoscopic surgical field. The two dimensional reconstruction data of 124 normal infants' airways were extracted from the medical image database of Beijing Children's Hospital for statistical analysis. After using linear fitting and goodness-of-fit test, a good linear relationship was detected between infant age and various parameters related to aid in designing a new BB for infants (R2=0.502). According to the growth and development rate of infants, the DICOM files of airway CT scan of 7 infants aged 30, 60, 90, 120, 180, 270, and 360 days were selected to print non-transparent convex and transparent concave 3D models. The non-transparent convex model was precisely measured to obtain the important parameters for BB design infants only, to complete the design of BB, to generate the sample, and to verify the blocking effect of produced sample in transparent concave three-dimensional (3D) model.

Erratum to Application of magnetic resonance neurography in neonatal brachial plexus injury: A case report and literature review [Radiology Case Reports 17 (2022) 2859-2862].

[This corrects the article DOI: 10.1016/j.radcr.2022.04.017.].

Application of magnetic resonance neurography in neonatal brachial plexus injury: A case report and literature review.

Neonatal obstetric brachial plexus palsy is common in newborns with fetal macrosomia, especially those who are delivered vaginally with shoulder dystocia or breech delivery. The anatomical structure of brachial plexus in newborns is thin, and it is neither collinear nor coplanar in space; The location, the type and degree of neonatal brachial plexus injury need to be comprehensively judged by clinical history, neurological and imaging examination. Conventional MR imaging is not sufficient to diagnose brachial plexus injury. In this case report, we describe the clinical and imaging data of a newborn with brachial plexus injury diagnosed by the fat-suppressed T2-weighted sequence and MR myelography and confirmed by surgery. In addition, we review the related literature in an attempt to provide a better understanding of the principles and characteristics of neonatal brachial plexus injury diagnosed by magnetic resonance neurography.

A combination vaccine against SARS-CoV-2 and H1N1 influenza based on receptor binding domain trimerized by six-helix bundle fusion core.

BACKGROUND: Increasing severe morbidity and mortality by simultaneous or sequential infections with SARS-CoV-2 and influenza A viruses (IAV), especially in the elderly and obese patients, highlight the urgency of developing a combination vaccine against COVID-19 and influenza. METHODS: Self-assembling SARS-CoV-2 RBD-trimer and Influenza H1N1 HA1-trimer antigens were constructed, upon the stable fusion core in post-fusion conformation. Immunogenicity of SARS-CoV-2 RBD-trimer vaccine and H1N1 HA1-trimer antigens candidates were evaluated in mice. Protection efficacy of a combination vaccine candidate against SARS-CoV-2 and IAV challenge was identified using the K18-hACE2 mouse model. FINDINGS: Both the resultant RBD-trimer for SARS-CoV-2 and HA1-trimer for H1N1 influenza fully exposed receptor-binding motifs (RBM) or receptor-binding site (RBS). Two-dose RBD-trimer induced significantly higher binding and neutralizing antibody titers, and also a strong Th1/Th2 balanced cellular immune response in mice. Similarly, the HA1-trimer vaccine was confirmed to exhibit potent immunogenicity in mice. A combination vaccine candidate, composed of RBD-trimer and HA1-trimer, afforded high protection efficacy in mouse models against stringent lethal SARS-CoV-2 and homogenous H1N1 influenza co-infection, characterized by 100% survival rate. INTERPRETATION: Our results represent a proof of concept for a combined vaccine candidate based on trimerized receptor binding domain against co-epidemics of COVID-19 and influenza. FUNDING: This project was funded by the Strategic Priority Research Program of CAS (XDB29040201), the National Natural Science Foundation of China (81830050, 81901680, and 32070569) and China Postdoctoral Science Foundation (2021M703450).

Ethylene Promotes Expression of the Appressorium- and Pathogenicity-Related Genes via GPCR- and MAPK-Dependent Manners in Colletotrichum gloeosporioides.

Ethylene (ET) represents a signal that can be sensed by plant pathogenic fungi to accelerate their spore germination and subsequent infection. However, the molecular mechanisms of responses to ET in fungi remain largely unclear. In this study, Colletotrichum gloeosporioides was investigated via transcriptomic analysis to reveal the genes that account for the ET-regulated fungal development and virulence. The results showed that ET promoted genes encoding for fungal melanin biosynthesis enzymes, extracellular hydrolases, and appressorium-associated structure proteins at 4 h after treatment. When the germination lasted until 24 h, ET induced multiple appressoria from every single spore, but downregulated most of the genes. Loss of selected ET responsive genes encoding for scytalone dehydratase (CgSCD1) and cerato-platanin virulence protein (CgCP1) were unable to alter ET sensitivity of C. gloeosporioides in vitro but attenuated the influence of ET on pathogenicity. Knockout of the G-protein-coupled receptors CgGPCR3-1/2 and the MAPK signaling pathway components CgMK1 and CgSte11 resulted in reduced ET sensitivity. Taken together, this study in C. gloeosporioides reports that ET can cause transcription changes in a large set of genes, which are mainly responsible for appressorium development and virulence expression, and these processes are dependent on the GPCR and MAPK pathways.