CE-BLAST makes it possible to compute antigenic similarity for newly emerging pathogens

Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra-or inter-subtypic pathogens, especially for the newly emerging varieties. Here we propose a computational method, Conformational Epitope (CE)-BLAST, for calculating the antigenic similarity among different pathogens with stable and high performance, which is independent of the prior binding-assay information, unlike the currently available models that heavily rely on the historical experimental data. Tool validation incorporates influenza-related experimental data sufficient for stability and reliability determination. Application to dengue-related data demonstrates high harmonization between the computed clusters and the experimental serological data, undetectable by classical grouping. CE-BLAST identifies the potential cross-reactive epitope between the recent zika pathogen and the dengue virus, precisely corroborated by experimental data. The high performance of the pathogens without the experimental binding data suggests the potential utility of CE-BLAST to rapidly design cross-protective vaccines or promptly determine the efficacy of the currently marketed vaccine against emerging pathogens, which are the critical factors for containing emerging disease outbreaks.Peer reviewe

Proteochemometric Modeling of the Antigen-Antibody Interaction : New Fingerprints for Antigen, Antibody and Epitope-Paratope Interaction

Despite the high specificity between antigen and antibody binding, similar epitopes can be recognized or cross-neutralized by paratopes of antibody with different binding affinities. How to accurately characterize this slight variation which may or may not change the antigen-antibody binding affinity is a key issue in this area. In this report, by combining cylinder model with shell structure model, a new fingerprint was introduced to describe both the structural and physical-chemical features of the antigen and antibody protein. Furthermore, beside the description of individual protein, the specific epitope-paratope interaction fingerprint (EPIF) was developed to reflect the bond and the environment of the antigen-antibody interface. Finally, Proteochemometric Modeling of the antigen-antibody interaction was established and evaluated on 429 antigen-antibody complexes. By using only protein descriptors, our model achieved the best performance (R-2 = 0: 91; Q(test)(2) = 0: 68) among peers. Further, together with EPIF as a new cross-term, our model (R-2 = 0: 92; Q(2) test = 0: 74) can significantly outperform peers with multiplication of ligand and protein descriptors as a cross-term (R2Peer reviewe

Mechanism of Bazhen decoction in the treatment of colorectal cancer based on network pharmacology, molecular docking, and experimental validation

ObjectiveBazhen Decoction (BZD) is a common adjuvant therapy drug for colorectal cancer (CRC), although its anti-tumor mechanism is unknown. This study aims to explore the core components, key targets, and potential mechanisms of BZD treatment for CRC.MethodsThe Traditional Chinese Medicine Systems Pharmacology (TCMSP) was employed to acquire the BZD’s active ingredient and targets. Meanwhile, the Drugbank, Therapeutic Target Database (TTD), DisGeNET, and GeneCards databases were used to retrieve pertinent targets for CRC. The Venn plot was used to obtain intersection targets. Cytoscape software was used to construct an “herb-ingredient-target” network and identify core targets. GO and KEGG pathway enrichment analyses were conducted using R language software. Molecular docking of key ingredients and core targets of drugs was accomplished using PyMol and Autodock Vina software. Cell and animal research confirmed Bazhen Decoction efficacy and mechanism in treating colorectal cancer.ResultsBZD comprises 173 effective active ingredients. Using four databases, 761 targets related to CRC were identified. The intersection of BZD and CRC yielded 98 targets, which were utilized to construct the “herb-ingredient-target” network. The four key effector components with the most targets were quercetin, kaempferol, licochalcone A, and naringenin. Protein-protein interaction (PPI) analysis revealed that the core targets of BZD in treating CRC were AKT1, MYC, CASP3, ESR1, EGFR, HIF-1A, VEGFR, JUN, INS, and STAT3. The findings from molecular docking suggest that the core ingredient exhibits favorable binding potential with the core target. Furthermore, the GO and KEGG enrichment analysis demonstrates that BZD can modulate multiple signaling pathways related to CRC, like the T cell receptor, PI3K-Akt, apoptosis, P53, and VEGF signaling pathway. In vitro, studies have shown that BZD dose-dependently inhibits colon cancer cell growth and invasion and promotes apoptosis. Animal experiments have shown that BZD treatment can reverse abnormal expression of PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53 genes. BZD also increases the ratio of CD4+ T cells to CD8+ T cells in the spleen and tumor tissues, boosting IFN-γ expression, essential for anti-tumor immunity. Furthermore, BZD has the potential to downregulate the PD-1 expression on T cell surfaces, indicating its ability to effectively restore T cell function by inhibiting immune checkpoints. The results of HE staining suggest that BZD exhibits favorable safety profiles.ConclusionBZD treats CRC through multiple components, targets, and metabolic pathways. BZD can reverse the abnormal expression of genes such as PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53, and suppresses the progression of colorectal cancer by regulating signaling pathways such as PI3K-AKT, P53, and VEGF. Furthermore, BZD can increase the number of T cells and promote T cell activation in tumor-bearing mice, enhancing the immune function against colorectal cancer. Among them, quercetin, kaempferol, licochalcone A, naringenin, and formaronetin are more highly predictive components related to the T cell activation in colorectal cancer mice. This study is of great significance for the development of novel anti-cancer drugs. It highlights the importance of network pharmacology-based approaches in studying complex traditional Chinese medicine formulations

Microstructure and Performance of a Porous Polymer Membrane with a Copper Nano-Layer Using Vapor-Induced Phase Separation Combined with Magnetron Sputtering

Antibacterial metalized poly(vinylidene fluoride) (PVDF) porous membranes with a nano-layer were obtained via the method of vapor-induced phase separation combined with magnetron sputtering of copper. Magnetron sputtering has such advantages as high deposition rates, low substrate temperatures, and good adhesion of films on substrates. The influence brought by deposition time on the microstructure, hydrophobic property, copper distribution state, anti-biofouling, and permeation separation performance was investigated via atomic force microscopy (AFM), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray (EDX) spectrometry, contact angle measurements, and capillary flow porometry, along with the porosity, water flux, protein solution flux, rejection rate, water flux recovery rate, and antibacterial property. The results showed that copper particles formed island-type deposits on the membrane surface and were embedded into cross-section pores near the surface owning to the interconnection of pores. Subsequently, the water flux and protein solution flux declined, but the rejection rate and water flux recovery rate increased. Meanwhile, Cu-coated PVDF membranes exhibited an excellent antibacterial ability

Short-Period Variation of the Activity of Atmospheric Turbulence in the MLT Region over Langfang

In this paper, we investigate the activity of atmospheric turbulence in the MLT region and the relationship between the activity of atmospheric turbulence and atmospheric wave activity. We use data from the Langfang MF radar (39.4∘N, 116.7∘E) from July 2019 to June 2020 and NRLMSIS 2.0 to calculate the parameters of atmospheric wave activity and atmospheric turbulence energy dissipation rate (ε). Atmospheric ε is modulated by different periods at different altitudes, and while there are 12 h and 24 h periods at all altitudes, the main period is different at different altitudes. A comparison of the ε with atmospheric tide activity shows that tides have an effect on ε, and the influence of tides on ε may be different at different altitudes. The pattern of variation in ε is similar to that of the atmospheric activity of the gravity wave, with both ε and the atmospheric activity of the gravity wave showing significant semi-annual variation

Endothelialized microvessels fabricated by microfluidics facilitate osteogenic differentiation and promote bone repair

In bone tissue engineering, vascularization is one of the critical factors that limit the effect of biomaterials for bone repair. While various approaches have been tried to build vascular networks in bone grafts, lack of endothelialization still constitutes a major technical hurdle. In this study, we have developed a facile technique to fabricate endothelialized biomimetic microvessels (BMVs) from alginate-collagen composite hydrogels within a single step using microfluidic technology. BMVs with different sizes could be readily prepared by adjusting the flow rate of microfluids. All BMVs supported perfusion and outward penetration of substances in the tube. Endothelial cells could adhere and proliferate on the inner wall of tubes. It was also found that the expression of CD31 and secretion of BMP-2 and PDGF-BB were higher in the rat umbilical vein endothelial cells (RUVECs) in BMVs than those cultured on hydrogel. When co-cultured with bone marrow mesenchymal stem cells (BMSCs), endothelialized BMVs promoted the osteogenic differentiation of BMSCs compared to those in acellular BMV group. In vivo, markedly enhanced new bone formation was achieved by endothelialized BMVs in a rat critical-sized calvarial defect model compared to those with non-endothelialized BMVs or without BMVs. Together, findings from both in vitro and in vivo studies have proven that endothelialized BMVs function to facilitate osteogenesis and promote bone regeneration, and therefore might present an effective strategy in bone tissue engineering. Statement of significance: In bone tissue engineering, limited vascularization is one of the critical factors that limit the effect of biomaterials for bone repair. In this study, we developed a facile technique to fabricate endothelialized biomimetic microvessels (BMVs) from alginate-collagen composite hydrogels within a single step using microfluidic technology. Both in vitro and in vivo studies have proven that endothelialized BMVs function to facilitate osteogenesis and promote bone regeneration, and therefore might present an effective strategy in bone tissue engineering