ABSTRACT
BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is considered a promising method in lung lesion assessment. METHODS: Sixty-four patients with single pulmonary lesions (SPLs) received DCE-MRI at 3.0 T. Of them, 49 cases were diagnosed with lung cancer, and 15 with benign pulmonary nodules (8 inflammatory nodules, 5 tuberculosis, and 2 abscesses). SPLs were quantitatively analyzed to determine the pulmonary lesions-related perfusion parameters, including reflux constant (Kep), volume transfer constant (Ktrans), the maximum slope of increase (MaxSlope), extravascular extracellular space volume fraction (Ve), apparent diffusion coefficient (ADC), the initial area in the signal intensity-time curve (IAUGC), and contrast-enhancement ratio (CER). In addition, a Student's t-test was conducted to calculate statistical significance regarding the quantitatively analyzed perfusion parameters in benign SPLs compared to malignant SPLs. The area under (AUC) the receiver operating characteristic (ROC) curve was studied to investigate the performance of perfusion parameters in diagnosing lung cancer. RESULTS: Values of Ktrans, Kep, Ve, MaxSlope, and IAUGC increased within malignant nodules relative to benign nodules (Ktrans: 0.21 ±0.08 vs. 0.73 ±0.40, P = 0.0001; Kep: 1.21 ±0.66 vs. 1.83 ±0.90, P = 0.0163; Ve: 0.24 ±0.08 vs. 0.47 ±0.18, P < 0.0001; MaxSlope: 0.09 ±0.14 vs. 0.28 ±0.29, P = 0.0166; IAUGC: 0.18 ±0.09 vs. 0.55 ±0.34, P = 0.0001). Meanwhile, malignant nodules presented higher ADC than benign nodules (0.0016 ±0.0006 vs. 0.0012 ±0.0003, P = 0.0019). Ktrans and IAUGC showed the best diagnostic performance with AUCs [1.0, 95%CI (0.99-1.0); 0.93, 95%CI(0.85-1.0), respectively]. CONCLUSION: Malignant pulmonary lesions had higher values of Ktrans, Ve, Kep, MaxSlope, and IAUGC compared to benign pulmonary lesions. Overall, perfusion parameters of DCE-MRI facilitate discrimination between benign from malignant pulmonary nodules.
ABSTRACT
SARS-CoV-2 infection is initiated with Spike glycoprotein binding to the receptor of human angiotensin converting enzyme 2 via its receptor binding domain. Blocking this interaction is considered as an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody, VHH60, directly produced from a humanized synthetic nanobody library. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein with a KD of 2.56 nM, inhibits infections of both live SARS-CoV-2 and pseudotyped viruses harboring wildtype, escape mutations and prevailing variants at nanomolar level. VHH60 also suppresses SARS-CoV-2 infection and propagation 50-fold better and protects mice from death two times longer than that of control group after live virus inoculation on mice. VHH60 therefore is a powerful synthetic nanobody with a promising profile for disease control against COVID19.
ABSTRACT
Most COVID-19 patients can build effective humoral immunity against SARS-CoV-2 after recovery(1, 2). However, it remains unknown how long the protection can maintain and how efficiently it can protect people from the reinfection of the emerging SARS-CoV-2 variants. Here we evaluated the sera from 248 COVID-19 convalescents around one year post-infection in Wuhan, the earliest epicenter of SARS-CoV-2. We demonstrated that the SARS-CoV-2 immunoglobulin G (IgG) maintains at a high level and potently neutralizes the infection of the original strain (WT) and the B.1.1.7 variant in most patients. However, they showed varying degrees of efficacy reduction against the other variants of concern (P.1, B.1.525, and especially B.1.351) in a patient-specific manner. Mutations in RBD including K417N, E484K, and E484Q/L452R (B.1.617) remarkably impair the neutralizing activity of the convalescents sera. Encouragingly, we found that a small fraction of patients sera showed broad neutralization potency to multiple variants and mutants, suggesting the existence of broadly neutralizing antibodies recognizing the epitopes beyond the mutation sites. Our results suggest that the SARS-CoV-2 vaccination effectiveness relies more on the timely re-administration of the epitope-updated vaccine than the durability of the neutralizing antibodies.
ABSTRACT
The upcoming flu season in the northern hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental co-infection of IAV with either pseudotyped or SARS-CoV-2 live virus, we found that IAV pre-infection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice co-infected with IAV in vivo. Moreover, such enhancement of SARS-CoV-2 infectivity was not seen with several other viruses probably due to a unique IAV segment as an inducer to elevate ACE2 expression. This study illustrates that IAV has a special nature to aggravate SARS-CoV-2 infection, and prevention of IAV is of great significance during the COVID-19 pandemic.
ABSTRACT
Bats are the suggested natural hosts for severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2, the latter of which caused the coronavirus disease 2019 (COVID-19) pandemic. The interaction of viral Spike proteins with their host receptor angiotensin-converting enzyme 2 (ACE2) is a critical determinant of potential hosts and cross-species transmission. Here we use virus-host receptor binding and infection assays to show that ACE2 orthologs from 24, 21, and 16 of 46 phylogenetically diverse bat species - including those in close and distant contact with humans - do not support entry of SARS-CoV, SARS-CoV-2, and both of these coronaviruses, respectively. Furthermore, we used genetic and functional analyses to identify genetic changes in bat ACE2 receptors associated with viral entry restrictions. Our study demonstrates that many - if not most - bat species are not potential hosts of SARS-CoV and SARS-CoV-2, and provides important insights into pandemic control and wildlife conservation.
ABSTRACT
Objective To study the characteristics of MRI Lesions in posterior circulation cerebral infarction and the correlation of the syndrome types of traditional Chinese medicine.Methods 82 patients with posterior circulation cerebral infarction from May 2012 to May 2015 were recruited, two observers estimated cranial MRI infarct size, location, and TCM syndrome type in the hospital medical records of the patients separately.Results Of all patients with posterior circulation cerebral infarction, patients with meridians involved infarction in the distant part of posterior circulation is far more than other parts of the posterior circulation(21 patient,P=0.006), nevertheless,patients with apoplexy involving Zang-fu organs,cerebral infarction volume is larger (14.78 ± 5.68 mlvs. 9.12 ± 6.67 ml,P=0.001).Conclusion Of all patients with posterior cerebral infarction, patients with meridians be involved, infarction in the distant part of posterior circulation is far more than other parts of the posterior circulation, nevertheless, in patients with apoplexy involving Zang-fu Organs, cerebral infarction volume is larger.
