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Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an infectious disease that has become a serious burden on global public health. This study screened and yielded specific nanobodies (Nbs) against SARS-CoV-2 spike protein receptor binding domain (RBD), following testing its basic characteristics. A nanobody phage library was established by immunizing a camel with RBD protein. After three rounds of panning, the positive colonies were screened by enzyme-linked immunosorbent assay (ELISA). By sequencing, four different sequences of nanobody gene fragments were selected. The four nanobody fusion proteins were expressed and purified, respectively. The specificity and affinity of the four nanobodies were identified by ELISA. Our results showed that an immune phage display library against SARS-CoV-2 has been successfully constructed with a library capacity of which was 4.7 × 108 CFU. The four purified nanobodies showed specific high-affinity binding SARS-CoV-2 S-RBD. Among these, the antigen binding affinity of Nb61 was more comparable to that of commercial rabbit anti-SARS-CoV-2 S-RBD antibodies. In sum, our study has obtained four nanobody strains against SARS-CoV-2 S-RBD with significant affinity and specificity, therefore laying an essential foundation for further research as well as the applications of diagnostic and therapeutic tools of SARS-CoV-2.

In order to explore the application of fluid mechanics technology in water conservancy and hydropower stations, the author proposes the study of hydraulic engineering fluid mechanics model based on trigonometric function relationship equation. According to standard k- ε Double equation and Reynolds time average (N-S) equation, given the runner boundary conditions, establish the mathematical model of the internal flow of the hydraulic turbine. Through CFD simulation technology, the runner of hydraulic turbine is numerically simulated to obtain the velocity distribution and blade pressure distribution inside the runner, movable guide vane and fixed guide vane, the reliability of the design is improved, and the application of CFD technology in hydropower project is analyzed with an example. The results show that, when the diameter of guide vane distribution circle is 4760mm, the scheme is optimal, and the relative efficiency under the optimal working condition is 96.35%. The flow of the modified runner from the inlet of the volute to the outlet of the draft tube is very stable under the optimal working condition, and there is no obvious vortex, especially there is no obvious vortex belt and vortex at the outlet of the runner; There is no obvious vortex in the draft tube, the flow on both sides of the pier is very uniform, and the flow on one side is not significantly greater than that on the other side, which fully shows that the flow performance of the modified runner is good. After reconstruction, the runner outlet flow field is good, and the internal flow line of the draft tube is smooth. The application prospect of hydrodynamic algorithm for hydraulic engineering is relatively broad.

Worldwide, over 800 million people are affected by kidney disease, yet its pathogenesis remains elusive, hindering the development of novel therapeutics. In this study, we used kidney-specific expression of quantitative traits and single-nucleus open chromatin analysis to show that genetic variants linked to kidney dysfunction on chromosome 20 target the acyl-CoA synthetase short-chain family 2 (ACSS2). By generating ACSS2-KO mice, we demonstrated their protection from kidney fibrosis in multiple disease models. Our analysis of primary tubular cells revealed that ACSS2 regulated de novo lipogenesis (DNL), causing NADPH depletion and increasing ROS levels, ultimately leading to NLRP3-dependent pyroptosis. Additionally, we discovered that pharmacological inhibition or genetic ablation of fatty acid synthase safeguarded kidney cells against profibrotic gene expression and prevented kidney disease in mice. Lipid accumulation and the expression of genes related to DNL were elevated in the kidneys of patients with fibrosis. Our findings pinpoint ACSS2 as a critical kidney disease gene and reveal the role of DNL in kidney disease., Introduction Over 800 million people in the world have chronic kidney disease (CKD) (1). CKD is a major cause of cardiovascular death and if left untreated leads to end-stage kidney [...]

Mineralocorticoid excess commonly leads to hypertension (HTN) and kidney disease. In our study, we used single- cell expression and chromatin accessibility tools to characterize the mineralocorticoid target genes and cell types. We demonstrated that mineralocorticoid effects were established through open chromatin and target gene expression, primarily in principal and connecting tubule cells and, to a lesser extent, in segments of the distal convoluted tubule cells. We examined the kidney-protective effects of steroidal and nonsteroidal mineralocorticoid antagonists (MRAs), as well as of amiloride, an epithelial sodium channel inhibitor, in a rat model of deoxycorticosterone acetate, unilateral nephrectomy, and high-salt consumption-induced HTN and cardiorenal damage. All antihypertensive therapies protected against cardiorenal damage. However, finerenone was particularly effective in reducing albuminuria and improving gene expression changes in podocytes and proximal tubule cells, even with an equivalent reduction in blood pressure. We noted a strong correlation between the accumulation of injured/profibrotic tubule cells expressing secreted posphoprotein 1 (Spp1), Il34, and platelet-derived growth factor subunit b (Pdgfb) and the degree of fibrosis in rat kidneys. This gene signature also showed a potential for classifying human kidney samples. Our multiomics approach provides fresh insights into the possible mechanisms underlying HTN-associated kidney disease, the target cell types, the protective effects of steroidal and nonsteroidal MRAs, and amiloride., Introduction Chronic kidney disease (CKD) is a serious and growing public health issue, affecting approximately 14% of the population in the United States (1). It is the ninth leading cause [...]

Head and neck squamous cell carcinoma (HNSCC) is a solid tumor with high morbidity. In recent years, traditional treatment methods, such as surgery, chemotherapy, and radiotherapy, are going through a bottleneck period, and therefore, new treatment methods are urgently needed to improve the prognosis of patients. Immunotherapy is an emerging treatment method for tumor in recent years, and immune checkpoint inhibitors (ICIs) have been widely used in the clinical treatment of HNSCC and other tumors with a marked clinical effect. This article summarizes the research advances in ICIs in the treatment of HNSCC and the effect of ICIs combined with radiotherapy and/or chemotherapy and elaborates on the adverse reactions of ICI the-rapy, in order to find the best paradigm of immunotherapy for HNSCC patients.