Experimental study of time response of bending deformation of bone cantilevers in an electric field

Bone is a complex composite material with hierarchical structures and anisotropic mechanical properties. Bone also processes electromechanical properties, such as piezoelectricity and streaming potentials, which termed as stress generated potentials. Furthermore, the electrostrictive effect and flexoelectric effect can also affect electromechanical properties of the bone. In the present work, time responses of bending deflections of bone cantilever in an external electric field are measured experimentally to investigate bone's electromechanical behavior. It is found that, when subjected to a square waveform electric field, a bone cantilever specimen begins to bend and its deflection increases gradually to a peak value. Then, the deflection begins to decrease gradually during the period of constant voltage. To analyze the reasons of the bending response of bone, additional experiments were performed. Experimental results obtained show the following two features. The first one is that the electric polarization, induced in bone by an electric field, is due to the Maxwell-Wagner polarization mechanism that the polarization rate is relatively slow, which leads to the electric field force acted on a bone specimen increase gradually and then its bending deflections increase gradually. The second one is that the flexoelectric polarization effect that resists the electric force to decrease and then leads to the bending deflection of a bone cantilever decrease gradually. It is concluded that the first aspect refers to the organic collagens decreasing the electric polarization rate of the bone, and the second one to the inorganic component influencing the bone's polarization intensity.The work was supported by the National Natural Science Foundation of China under Grant No. 11372218

Induction of WNT16 via peptide-mRNA nanoparticle-based delivery maintains cartilage homeostasis

Osteoarthritis (OA) is a progressive joint disease that causes significant disability and pain and for which there are limited treatment options. We posit that delivery of anabolic factors that protect and maintain cartilage homeostasis will halt or retard OA progression. We employ a peptide-based nanoplatform to deliver Wingless and the name Int-1 (WNT) 16 messenger RNA (mRNA) to human cartilage explants. The peptide forms a self-assembled nanocomplex of approximately 65 nm in size when incubated with WNT16 mRNA. The complex is further stabilized with hyaluronic acid (HA) for enhanced cellular uptake. Delivery of peptide-WNT16 mRNA nanocomplex to human cartilage explants antagonizes canonical β-catenin/WNT3a signaling, leading to increased lubricin production and decreased chondrocyte apoptosis. This is a proof-of-concept study showing that mRNA can be efficiently delivered to articular cartilage, an avascular tissue that is poorly accessible even when drugs are intra-articularly (IA) administered. The ability to accommodate a wide range of oligonucleotides suggests that this platform may find use in a broad range of clinical applications

Iron and nickel doped CoSe2 as efficient non precious metal catalysts for oxygen reduction

Iron and nickel doped CoSe2 were prepared by solvothermal method, and they were proved to be ternary chalcogenides by series of physical characterization. The effects of the iron and nickel contents on the oxygen reduction reaction were investigated by electrochemical measurements, and the highest activities were obtained on Co0.7Fe0.3Se2 and Co0.7Ni0.3Se2, respectively. Both Co0.7Fe0.3Se2 and Co0.7Ni0.3Se2 presented four-electron pathway. Furthermore, Co0.7Fe0.3Se2 exhibited more positive cathodic peak potential (0.564 V) and onset potential (0.759 V) than these of Co0.7Ni0.3Se2 (0.558 V and 0.741 V). And Co0.7Fe0.3Se2 displayed even superior stability and better tolerance to methanol, ethanol and ethylene glycol crossover effects than the commercial Pt/C (20 wt% Pt)

Synthesis of CoSe2-SnSe2 nanocube-coated nitrogen-doped carbon (NC) as anode for lithium and sodium ion batteries

CoSe2-SnSe2/NC nanocubes (CSNC@NC) coated by nitrogen-doped carbon (NC) were synthesized successfully by an ordinary pyrazole polymerization and carbonization process. In comparison with bare CSNC, the CSNC@NC composite exhibited good structural stability and improved electrical conductivity when used as anode. The CSNC@NC electrode showed a stable Li storage capacity (730.41 mAh g−1 over 100 cycles at 0.2 A g−1) and excellent rate performance (402.10 mAh g−1 at 2 A g−1). For Na storage, the discharge capacity could be maintained 279.3 mAh g−1 over 100 cycles at 0.2 A g−1; the lower capacity than that for Li storage maybe caused by the larger size of Na+ ions. The excellent cycling stability for both Li and Na storage cycle ability may be attributed to the carbon layer, which could tolerated the volume fluctuations and ensured the structural integrity of the CSNC during the charge/discharge process; Moreover, the improved electrical conductivity accelerated the diffusion rate of both Li+ and Na+, which is conducive to the electrochemical reactions in their respective batteries. This unique structure and preeminent electrochemical performance of CSNC@NC show that CSNC@NC is a promising anode material for high-efficiency Li ion and Na ion batteries

Plasma metabolomic profiles predict near-term death among individuals with lower extremity peripheral arterial disease

BackgroundIndividuals with peripheral arterial disease (PAD) have a nearly two-fold increased risk of all-cause and cardiovascular disease mortality compared to those without PAD. This pilot study determined whether metabolomic profiling can accurately identify patients with PAD who are at increased risk of near-term mortality.MethodsWe completed a case-control study using 1H NMR metabolomic profiling of plasma from 20 decedents with PAD, without critical limb ischemia, who had blood drawn within 8 months prior to death (index blood draw) and within 10 to 28 months prior to death (preindex blood draw). Twenty-one PAD participants who survived more than 30 months after their index blood draw served as a control population.ResultsResults showed distinct metabolomic patterns between preindex decedent, index decedent, and survivor samples. The major chemical signals contributing to the differential pattern (between survivors and decedents) arose from the fatty acyl chain protons of lipoproteins and the choline head group protons of phospholipids. Using the top 40 chemical signals for which the intensity was most distinct between survivor and preindex decedent samples, classification models predicted near-term all-cause death with overall accuracy of 78% (32/41), a sensitivity of 85% (17/20), and a specificity of 71% (15/21). When comparing survivor with index decedent samples, the overall classification accuracy was optimal at 83% (34/41) with a sensitivity of 80% (16/20) and a specificity of 86% (18/21), using as few as the top 10 to 20 chemical signals.ConclusionsOur results suggest that metabolomic profiling of plasma may be useful for identifying PAD patients at increased risk for near-term death. Larger studies using more sensitive metabolomic techniques are needed to identify specific metabolic pathways associated with increased risk of near-term all-cause mortality among PAD patients

Rapamycin perfluorocarbon nanoparticle mitigates cisplatin-induced acute kidney injury

For nearly five decades, cisplatin has played an important role as a standard chemotherapeutic agent and been prescribed to 10-20% of all cancer patients. Although nephrotoxicity associated with platinum-based agents is well recognized, treatment of cisplatin-induced acute kidney injury is mainly supportive and no specific mechanism-based prophylactic approach is available to date. Here, we postulated that systemically delivered rapamycin perfluorocarbon nanoparticles (PFC NP) could reach the injured kidneys at sufficient and sustained concentrations to mitigate cisplatin-induced acute kidney injury and preserve renal function. Using fluorescence microscopic imaging and fluorine magnetic resonance imaging/spectroscopy, we illustrated that rapamycin-loaded PFC NP permeated and were retained in injured kidneys. Histologic evaluation and blood urea nitrogen (BUN) confirmed that renal structure and function were preserved 48 h after cisplatin injury. Similarly, weight loss was slowed down. Using western blotting and immunofluorescence staining, mechanistic studies revealed that rapamycin PFC NP significantly enhanced autophagy in the kidney, reduced the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as decreased the expression of the apoptotic protein Bax, all of which contributed to the suppression of apoptosis that was confirmed with TUNEL staining. In summary, the delivery of an approved agent such as rapamycin in a PFC NP format enhances local delivery and offers a novel mechanism-based prophylactic therapy for cisplatin-induced acute kidney injury

Integrative analyses of a mitophagy-related gene signature for predicting prognosis in patients with uveal melanoma

We aimed to create a mitophagy-related risk model via data mining of gene expression profiles to predict prognosis in uveal melanoma (UM) and develop a novel method for improving the prediction of clinical outcomes. Together with clinical information, RNA-seq and microarray data were gathered from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ConsensusClusterPlus was used to detect mitophagy-related subgroups. The genes involved with mitophagy, and the UM prognosis were discovered using univariate Cox regression analysis. In an outside population, a mitophagy risk sign was constructed and verified using least absolute shrinkage and selection operator (LASSO) regression. Data from both survival studies and receiver operating characteristic (ROC) curve analyses were used to evaluate model performance, a bootstrap method was used test the model. Functional enrichment and immune infiltration were examined. A risk model was developed using six mitophagy-related genes (ATG12, CSNK2B, MTERF3, TOMM5, TOMM40, and TOMM70), and patients with UM were divided into low- and high-risk subgroups. Patients in the high-risk group had a lower chance of living longer than those in the low-risk group (p < 0.001). The ROC test indicated the accuracy of the signature. Moreover, prognostic nomograms and calibration plots, which included mitophagy signals, were produced with high predictive performance, and the risk model was strongly associated with the control of immune infiltration. Furthermore, functional enrichment analysis demonstrated that several mitophagy subtypes may be implicated in cancer, mitochondrial metabolism, and immunological control signaling pathways. The mitophagy-related risk model we developed may be used to anticipate the clinical outcomes of UM and highlight the involvement of mitophagy-related genes as prospective therapeutic options in UM. Furthermore, our study emphasizes the essential role of mitophagy in UM