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The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the "immune-escape" Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.
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Objective : To evaluate the value of contrast-enhanced ultrasound quantitative analysis in the differential diagnosis of benign and malignant breast intraductal lesions. Methods ¡¤ A retrospective analysis was made on the characteristics of conventional ultrasound and the time-intensity curve (TIC) of contrast-enhanced ultrasound (CEUS) of 71 breast intraductal lesions in 63 patients, which were surgically resected and pathologically confirmed in Shanghai Tenth People’s Hospital from January 2016 to December 2018. The parameters of CEUS perfusion in the lesion area were obtained. Independent sample t test was used to analyze the differences of quantitative parameters between benign and ma-lignant lesions. The receiver operating characteristic (ROC) curve was used to evaluate the value of conventional ultrasound, quantitative analysis of CEUS and their combination for the differential diagnosis of benign and malignant intraductal lesions of breast. Results ¡¤ There were 42 benign lesions and 29 malignant lesions. Among the quantitative parameters of CEUS, time to peak (t=2.072, P=0.042), peak intensity (t=-2.629, P=0.011), rise slope rate (t=3.015, P=0.004) and the area under the curve (AUC) (t=3.308, P=0.001) were statistically significant. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value and area under the ROC curve of conventional ultrasound were 31.03%, 90.48%, 66.20%, 69.20%, 65.50% and 0.608. Those of quantitative analysis of CEUS were 75.86%, 71.43%, 73.24%, 64.70%, 81.10% and 0.776. And those of their combination were 86.21%, 97.62%, 92.96%, 96.15%, 91.11% and 0.943. Conclusion ¡¤ Conventional ultrasound is of limited value in the diagnosis of breast intraductal lesions, and quantitative analysis of CEUS is of great significance in differentiating benign from malignant breast intraductal lesions. The combination of conventional ultrasound and quantitative analysis of CEUS can significantly im-prove the diagnostic value.
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Objective:To investigate the changes of genus-level gut microbiome in patients with spinal cord injury and its significance in clinical rehabilitation. Methods:Fecal samples were collected from 23 patients with spinal cord injury (patients group) and 21 healthy volunteers (control group). Gut microbiome was detected by 16S rDNA high-throughput sequencing. Bioinformatics methods such as species composition analysis and Random Forest were used to analyze the distribution and difference of genus-level gut microbiome between two groups. Results:Compared with the control group, the increased important marker genera in the patients group were as follows: UBA1819, Ruminiclostridium 9, Ruminococcaceae NK4A214 group, Ruminococcus 2, Ruminococceae UCG-005, Ruminiclostridium 5, Flavonifractor belonging to Ruminococceae; Aglistes, dgA-11 gut group, Rikenaceae RC9 gut group belonging to Rikenellaceae; [Eubacterium] oxidoreducens group belonging to Lachnospiraceae; Intestinibacter belonging to Peptostreptococcaceae; Escherichia-Shigella belonging to Enterobacteriaceae; Tannerellaceae belonging to Parabacteroides (|U| > 1.962, P < 0.05). The decreased marker genera in the patients group was Fusobacterium of Fusobacteriaceae (|U| = -2.284, P < 0.05). Conclusion:There are significant differences of gut microbiome in spinal cord injury patients. The relative abundance of Ruminococcaceae relating to depression, Ruminococcus relating to central nervous system diseases, and enteropathogenic bacteria such as Escherichia-Shigella and Erysipelothrix increase; and the relative abundance of butyrate-producing bacteria and anti-inflammatory bacteria benefitting to the intestine decrease; which may play a role in clinic.
