Despite the recent availability of vaccines against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an urgent need for specific anti-SARS-CoV-2 drugs. Monoclonal neutralizing antibodies are an important drug class in the global fight against the SARS-CoV-2 pandemic due to their ability to convey immediate protection and their potential to be used as both prophylactic and therapeutic drugs. Clinically used neutralizing antibodies against respiratory viruses are currently injected intravenously, which can lead to suboptimal pulmonary bioavailability and thus to a lower effectiveness. Here we describe DZIF-10c, a fully human monoclonal neutralizing antibody that binds the receptor-binding domain of the SARS-CoV-2 spike protein. DZIF-10c displays an exceptionally high neutralizing potency against SARS-CoV-2, retains full activity against the variant of concern (VOC) B.1.1.7 and still neutralizes the VOC B.1.351, although with reduced potency. Importantly, not only systemic but also intranasal application of DZIF-10c abolished the presence of infectious particles in the lungs of SARS-CoV-2 infected mice and mitigated lung pathology when administered prophylactically. Along with a favorable pharmacokinetic profile, these results highlight DZIF-10c as a novel human SARS-CoV-2 neutralizing antibody with high in vitro and in vivo antiviral potency. The successful intranasal application of DZIF-10c paves the way for clinical trials investigating topical delivery of anti-SARS-CoV-2 antibodies.
Abstract:Heat is the product following the metabolism of cells, and the metabolism is closely related with the pathological information of living organism. So, there are strong ties between the heat distribution and the pathological state in living organism. In this paper, the mathematical function δ is introduced in the classical Pennes bio-heat transfer equation as the point heat source. By simplifying the boundary conditions, a novel bio-heat transfer model is established and solved in a spherical coordinate system. Based on the temperature distribution of human body surface, the information of heat source is mined layer by layer, and the corresponding q-r curve of heat intensity varying with depth is acquired combining the fitting method of Lorentz curve. According to a large number of clinical confirmed cases and statistics, the diagnostic criteria judging diseases by q-r curve are proposed. Five typical clinical practices are performed and four of the diagnosis results are very consistent with those of molybdenum target (MT) X-ray, B-ultrasonic images and pathological examination, one gives the result of early stage malignant tumor that MT X-ray and B-ultrasonic can't check out. It is a radiation-free green method with noninvasive diagnostic procedure and accurate diagnosis result.
This study aims to evaluate the feasibility and efficacy of quantitative diagnosis through thermal analysis of abnormal metabolism. In this paper, an analytical-based steady-state solution for the thermal inverse problem was developed, considering an equivalent point heat source embedded in the tissue. Based on this solution, we developed a simple and efficient algorithm that generates solutions for the nonlinear heat conduction model. Using the nonlinear fitting analysis, a regular distribution can be derived from the raw thermal patterns of the skin surface above the tumor, and the power and depth of the equivalent heat source can be derived to investigate whether the tumor is malignant or benign. The thermal power Q of internal heat source was estimated to predict the satisfactory approaches to distinguish between benign and malignant tumors. The results of four clinical cases (female patients with malignant tumor and benign tumor) show that the estimated values of the power of the heat sources in malignant cases (fatty: Q = 0.34851 W; dense: Q = 0.46933 W) are both far greater than the ones in benign (fatty: Q = 0.04721 W; dense: Q = 0.07717 W), irregardless of the breast density. The correlation coefficients (R (2)) of the nonlinear curve fittings are all above 0.98. The new thermal method proposed in this study would help to improve the preciseness of diagnosis on breast masses (malignant or benign).
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