Biomimetic recombinant of red blood cell membranes for improved photothermal therapy

Background: RBC membrane derived nanoparticles (NPs) represent an emerging platform with prolonged circulation capacity for the delivery of active substances. For functionalize derived RBCs NPs, various strategies, such as biomimetic rebuilding of RBCs, chemical modification or inserting ligands, have been carried out to improve their performance. However, one potential adverse effect for these methods is the structural failure of membrane proteins, consequently affecting its original immune escape function. Results: In this study, we reported a green technology of “disassembly-reassembly” to prepare biomimetic reconstituted RBCs membrane (rRBCs) by separating the endogenous proteins and lipids from nature RBC membrane. IR780 iodide was used as a pattern drug to verify the property and feasibility of rRBCs by constructing IR780@rRBC NPs with IR780@RBC NPs and free IR780 as controls. The results demonstrated the superiority of IR780@rRBC NPs in toxicity, stability, pharmacokinetics and pharmacodynamics compared with IR780@rRBC and free IR780. Conclusions: The reported “disassembly-reassembly” strategy shows great potential to produce controllable and versatile rRBC membrane-inspired delivery platform, which may be used to overcome the deficiency of functionalization in cell membrane coated nanoparticles

Development and validation of a predictive nomogram for lower extremity deep vein thrombosis dislodgement in orthopedic patients

ObjectiveTo analyze the risk factors of lower extremity deep venous thrombosis (DVT) detachment in orthopedic patients, and to establish a risk nomogram prediction model.MethodsThe clinical data of 334 patients with orthopedic DVT admitted to the Third Hospital of Hebei Medical University from January 2020 to July 2021 were retrospectively analyzed. General statistics included gender, age, BMI, thrombus detachment, inferior vena cava filter window type, filter implantation time, medical history, trauma history, operation, use of tourniquet, thrombectomy, anesthesia mode, anesthesia grade, operative position, blood loss during operation, blood transfusion, immobilization, use of anticoagulants, thrombus side, thrombus range, D-dimer content before filter implantation and during removal of inferior vena cava filter. Logistic regression was used to perform univariate and multivariate analysis on the possible factors of thrombosis detachment, screen out independent risk factors, establish a risk nomogram prediction model by variables, and internally verify the predictability and accuracy of the model.ResultsBinary logistic regression analysis showed that Short time window filter (OR = 5.401, 95% CI = 2.338–12.478), lower extremity operation (OR = 3.565, 95% CI = 1.553–8.184), use of tourniquet (OR = 3.871, 95% CI = 1.733–8.651), non-strict immobilization (OR = 3.207, 95% CI = 1.387–7.413), non-standardized anticoagulation (OR = 4.406, 95% CI = 1.868–10.390), distal deep vein thrombosis (OR = 2.212, 95% CI = 1.047–4.671) were independent risk factors for lower extremity DVT detachment in orthopedic patients (P < 0.05). Based on these six factors, a prediction model for the risk of lower extremity DVT detachment in orthopedic patients was established, and the risk prediction ability of the model was verified. The C-index of the nomogram model was 0.870 (95% CI: 0.822–0.919). The results indicate that the risk nomogram model has good accuracy in predicting the loss of deep venous thrombosis in orthopedic patients.ConclusionThe nomogram risk prediction model based on six clinical factors, including filter window type, operation condition, tourniquet use, braking condition, anticoagulation condition, and thrombosis range, has good predictive performance

Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase

Metabolic networks are interconnected and influence diverse cellular processes. The protein-metabolite interactions that mediate these networks are frequently low affinity and challenging to systematically discover. We developed mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically (MIDAS) to identify such interactions. Analysis of 33 enzymes from human carbohydrate metabolism identified 830 protein-metabolite interactions, including known regulators, substrates, and products as well as previously unreported interactions. We functionally validated a subset of interactions, including the isoform-specific inhibition of lactate dehydrogenase by long-chain acyl-coenzyme A. Cell treatment with fatty acids caused a loss of pyruvate-lactate interconversion dependent on lactate dehydrogenase isoform expression. These protein-metabolite interactions may contribute to the dynamic, tissue-specific metabolic flexibility that enables growth and survival in an ever-changing nutrient environment

Expansion and Functional Divergence of AP2 Group Genes in Spermatophytes Determined by Molecular Evolution and Arabidopsis Mutant Analysis

The APETALA2 (AP2) genes represent the AP2 group within a large group of DNA-binding proteins called AP2/EREBP. The AP2 gene is functional and necessary for flower development, stem cell maintenance, and seed development, whereas the other members of AP2 group redundantly affect flowering time. Here we study the phylogeny of AP2 group genes in spermatophytes. Spermatophyte AP2 group genes can be classified into AP2 and TOE types, six clades, and we found that the AP2 group homologs in gymnosperms belong to the AP2 type, whereas TOE types are absent, which indicates the AP2 type gene are more ancient and TOE type was split out of AP2 type and losing the major function. In Brassicaceae, the expansion of AP2 and TOE type lead to the gene number of AP2 group were up to six. Purifying selection appears to have been the primary driving force of spermatophyte AP2 group evolution, although positive selection occurred in the AP2 clade. The transition from exon to intron of AtAP2 in Arabidopsis mutant leads to the loss of gene function and the same situation was found in AtTOE2. Combining this evolutionary analysis and published research, the results suggest that typical AP2 group genes may first appear in gymnosperms and diverged in angiosperms, following expansion of group members and functional differentiation. In angiosperms, AP2 genes (AP2 clade) inherited key functions from ancestors and other genes of AP2 group lost most function but just remained flowering time controlling in gene formation. In this study, the phylogenies of AP2 group genes in spermatophytes was analyzed, which supported the evidence for the research of gene functional evolution of AP2 group

Fabrication and Properties of Zn-3Mg-1Ti Alloy as a Potential Biodegradable Implant Material

A Zn-3Mg-1Ti alloy was fabricated by ultrasonic treatment of Zn-Mg alloy melt using a Ti ultrasonic radiation rod. The microstructure, phase structure, mechanical properties, degradation property, and in vitro cytotoxicity were investigated systematically. The obtained Zn-3Mg-1Ti alloy is composed of the Zn, Mg2Zn11, and TiZn16. Owing to the grain refinement and second phase reinforcement, the mechanical properties of Zn-3Mg-1Ti alloy is improved. In addition, the Zn-3Mg-1Ti alloy exhibits minimal cytotoxicity compared to pure Zn and Zn-1Ti alloy. Electrochemical tests show that the Zn-3Mg-1Ti alloy has an appropriate degradation rate in Hank’s solution

Kinetics, Thermodynamics and Mechanism of Enzymatic Degradation of Zearalenone in Degummed Corn Oil

The kinetics and thermodynamics of the enzymatic degradation of zearalenone (ZEN) in degummed corn oil were investigated by analyzing the impacts of temperature, pH, ZEN hydrolase dosage and ZEN concentration on the initial reaction rate. The kinetic study found that the maximum reaction rate was 0.97 μmol × kg−1 min−1, the Michaelis constant (Km) was 11,476 μmol × kg−1 and the Michaelis equation was V = 0.97[S]/(11,476 + [S]). The thermodynamic study showed that the activation energy (Ea) was 70.37 kJ·mol−1, the activation enthalpy change of the reaction (ΔH) > 0, the free energy of activation (ΔG) > 0 and the activation entropy change (ΔS) 2O, followed by generating the intermediate W-ZEN-H2O under the action of a degrading enzyme. Then, the lactone bond was opened to produce C18H24O6, and finally the decarboxylation product C17H24O4 formed automatically