Modulation of SEMA4D-modified titanium surface on M2 macrophage polarization via activation of Rho/ROCK-mediated lactate release of endothelial cells: In vitro and in vivo.

SEMA4D-modified titanium surfaces can indirectly regulate macrophages through endothelial cells to achieve an anti-inflammatory effect, which is beneficial for healing soft tissues around the gingival abutment. However, the mechanism of surface-induced cellular phenotypic changes in SEMA4D-modified titanium has not yet been elucidated. SEMA4D activates the RhoA signaling pathway in endothelial cells, which coordinates metabolism and cytoskeletal remodeling. This study hypothesized that endothelial cells inoculated on SEMA4D-modified titanium surfaces can direct M2 polarization of macrophages via metabolites. An indirect co-culture model of endothelial cells and macrophages was constructed in vitro, and specific inhibitors were employed. Subsequently, endothelial cell adhesion and migration, metabolic changes, Rho/ROCK1 expression, and inflammatory expression of macrophages were assessed via immunofluorescence microscopy, specific kits, qRT-PCR, and Western blotting. Moreover, an in vivo rat bilateral maxillary implant model was constructed to evaluate the soft tissue healing effect. The in vitro experiments showed that the SEMA4D group had stronger endothelial cell adhesion and migration, increased Rho/ROCK1 expression, and enhanced release of lactate. Additionally, decreased macrophage inflammatory expression was observed. In contrast, the inhibitor group partially suppressed lactate metabolism and motility, whereas increased inflammatory expression. The in vivo analyses indicated that the SEMA4D group had faster and better angiogenic and anti-inflammatory effects, especially in the early stage. In conclusion, via the Rho/ROCK1 signaling pathway, the SEMA4D-modified titanium surface promotes endothelial cell adhesion and migration and lactic acid release, then the paracrine lactic acid promotes the polarization of macrophages to M2, thus obtaining the dual effects of angiogenesis and anti-inflammation.

Prediction of cardiovascular adverse events in newly diagnosed multiple myeloma: Development and validation of a risk score prognostic model.

Background: Multiple myeloma (MM) is the second most common hematological malignancy, and the treatments markedly elevate the survival rate of the patients in recent years. However, the prevalence of cardiovascular adverse events (CVAEs) in MM had been increasing recently. CVAEs in MM patients are an important problem that we should focus on. Clinical tools for prognostication and risk-stratification are needed. Patients and methods: This is a retrospective study that included patients who were newly diagnosed with multiple myeloma (NDMM) in Shanghai Changzheng Hospital and Affiliated Jinhua Hospital, Zhejiang University School of Medicine from June 2018 to July 2020. A total of 253 patients from two medical centers were divided into training cohort and validation cohort randomly. Univariable analysis of the baseline factors was performed using CVAEs endpoints. Multivariable analysis identified three factors for a prognostic model that was validated in internal validation cohorts. Results: Factors independently associated with CVAEs in NDMM were as follows: age>61 years old, high level of baseline office blood pressure, and left ventricular hypertrophy (LVH). Age contributed 2 points, and the other two factors contributed 1 point to a prognostic model. The model distinguished the patients into three groups: 3-4 points, high risk; 2 points, intermediate risk; 0-1 point, low risk. These groups had significant difference in CVAEs during follow-up days in both training cohort (p<0.0001) and validation cohort (p=0.0018). In addition, the model had good calibration. The C-indexes for the prediction of overall survival of CVAEs in the training and validation cohorts were 0.73 (95% CI, 0.67-0.79) and 0.66 (95% CI, 0.51-0.81), respectively. The areas under the receiver operating characteristic curve (AUROCs) of the 1-year CVAEs probability in the training and validation cohorts were 0.738 and 0.673, respectively. The AUROCs of the 2-year CVAE probability in the training and validation cohorts were 0.722 and 0.742, respectively. The decision-curve analysis indicated that the prediction model provided greater net benefit than the default strategies of providing assessment or not providing assessment for all patients. Conclusion: A prognostic risk prediction model for predicting CVAEs risk of NDMM patients was developed and internally validated. Patients at increased risk of CVAEs can be identified at treatment initiation and be more focused on cardiovascular protection in the treatment plan.

Iron(II) Metal-Organic Framework with unh Topology and Tetrazole-Padded Helical Channels.

A unique metal-organic framework (MOF) with tetrazole-padded helical channels has been successfully synthesized in one pot from iron(II) trifluoromethanesulfonate, 4-formylimidazole, hydrazine, and sodium azide under solvothermal conditions and features a rare unh topology and porous structure for gas adsorption. Transformations of condensation, cycloaddition, and coordination occurred during the synthetic process, in which a 1,5-disubstituted tetrazole ligand was formed in situ.

Hydroxo Iron(III) Sites in a Metal-Organic Framework: Proton-Coupled Electron Transfer and Catalytic Oxidation of Alcohol with Molecular Oxygen.

Metalloenzymes are powerful biocatalysts that can catalyze particular chemical reactions with high activity, selectivity, and specificity under mild conditions. Metal-organic frameworks (MOFs) composed of metal ions or metal clusters and organic ligands with defined cavities have the potential to impart enzyme-like catalytic activity and mimic metalloenzymes. Here, a new metal-organic framework implanted with hydroxo iron(III) sites with the structural and reactivity characteristics of iron-containing lipoxygenases is reported. Similar to lipoxygenases, the hydrogen atoms and electrons of the substrate can transfer to the hydroxo iron(III) sites, showing typical proton-coupled electron transfer behavior. In the reactivity mimicking biology system, similar to alcohol oxidase, the material also catalyses the oxidation of alcohol into aldehyde by using O2 with a high yield and 100% selectivity under mild conditions, without the use of a radical cocatalyst or photoexcitation. These results provide strong evidence for the high structural fidelity of enzymatically active sites in MOF materials, verifying that MOFs provide an ideal platform for designing biomimetic heterogeneous catalysts with high conversion efficiency and product selectivity.