Efficient Proton-exchange Membrane Fuel Cell Performance of Atomic Fe Sites via p-d Hybridization with Al Dopants.

Orbital hybridization to regulate the electronic structures and surface chemisorption properties of transition metals is of great importance for boosting the oxygen reduction reaction (ORR) in proton-exchange membrane fuel cells (PEMFCs). Herein, we developed a core-shell rambutan-like nanocarbon catalyst (FeAl-RNC) with atomically dispersed Fe-Al atom pairs from metal-organic framework (MOF) material. Experimental and theoretical results demonstrate that the strong p-d orbital hybridization between Al and Fe results in an asymmetric electron distribution with moderate adsorption strength of oxygen intermediates, rendering enhanced intrinsic ORR activity. Additionally, the core-shell rambutan-like structure of FeAl-RNC with abundant micropores and macropores can enhance the density of active sites, stability, and transport pathways in PEMFC. The FeAl-RNC-based PEMFC achieves excellent activity (68.4 mA cm-2 at 0.9 V), high peak power (1.05 W cm-2), and good stability with only 7% current loss after 100 h at 0.7 V under H2-O2 condition.

Sonochemical Synthesis of Natural Polyphenolic Nanoparticles for Modulating Oxidative Stress.

Natural polyphenolic compounds play a vital role in nature and are widely utilized as building blocks in the fabrication of emerging functional nanomaterials. Although diverse fabrication methodologies are developed in recent years, the challenges of purification, uncontrollable reaction processes and additional additives persist. Herein, a modular and facile methodology is reported toward the fabrication of natural polyphenolic nanoparticles. By utilizing low frequency ultrasound (40 kHz), the assembly of various natural polyphenolic building blocks is successfully induced, allowing for precise control over the particle formation process. The resulting natural polyphenolic nanoparticles possessed excellent in vitro antioxidative abilities and in vivo therapeutic effects in typical oxidative stress models including wound healing and acute kidney injury. This study opens new avenues for the fabrication of functional materials from naturally occurring building blocks, offering promising prospects for future advancements in this field.

Dual Activation for Tuning N, S Co-Doping in Porous Carbon Sheets Toward Superior Sodium Ion Storage.

Porous carbon has been widely focused to solve the problems of low coulombic efficiency (ICE) and low multiplication capacity of Sodium-ion batteries (SIBs) anodes. The superior energy storage properties of two-dimensional(2D) carbon nanosheets can be realized by modulating the structure, but be limited by the carbon sources, making it challenging to obtain 2D structures with large surface area. In this work, a new method for forming carbon materials with high N/S doping content based on combustion activation using the dual activation effect of K2SO4/KNO3 is proposed. The synthesized carbon material as an anode for SIBs has a high reversible capacity of 344.44 mAh g-1 at 0.05 A g-1. Even at the current density of 5 Ag-1, the capacity remained at 143.08 mAh g-1. And the ICE of sodium-ion in ether electrolytes is ≈2.5 times higher than that in ester electrolytes. The sodium storage mechanism of ether/ester-based electrolytes is further explored through ex-situ characterizations. The disparity in electrochemical performance can be ascribed to the discrepancy in kinetics, wherein ether-based electrolytes exhibit a higher rate of Na+ storage and shedding compared to ester-based electrolytes. This work suggests an effective way to develop doubly doped carbon anode materials for SIBs.

Association between Lactate Dehydrogenase to Albumin Ratio and 28-Day Mortality in Patients with Sepsis: a Retrospective Cohort Study.

BACKGROUND: This study aims to evaluate the lactate dehydrogenase to albumin ratio and mortality at 28 days in patients with sepsis. METHODS: Data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were used for this retrospective cohort analysis. The level of the lactate dehydrogenase to albumin ratio was recovered at admission and the outcome index was mortality at 28 days. Multivariate Cox regression, survival curve analysis, and subgroup analysis were used to study the relationship between lactate dehydrogenase to albumin ratio and 28-day mortality in sepsis patients. RESULTS: This study included a total of 4,265 patients with sepsis, with a 28-day mortality rate of 51.9%. After conducting multivariable COX regression analysis and adjusting for all potential confounding factors, we observed that compared to the LDH/ALB (Q1) group, the Q2 group had a 1.34-fold higher risk of 28-day mortality (HR = 1.34, 95% CI: 1.20 - 1.49, p < 0.001), while the Q3 group had a 1.90-fold higher risk (HR = 1.90, 95% CI: 1.69 - 2.14, p < 0.001). Furthermore, the survival analysis curve indicated a gradual increase in the 28-day mortality rate of septic patients as LDH/ALB levels increased. In addition, the ROC curve demonstrated that the area under the curve for LDH/ALB was 0.6507 (95% CI: 63.4991% - 66.6368%), which was higher than that of LDH (AUC = 0.6434), ALB (AUC = 0.55), and SOFA SCORE (AUC = 0.5564). Finally, subgroup analysis revealed no significant interaction between LDH/ALB and the various subgroups. CONCLUSIONS: The LDH/ALB ratio is significantly correlated with mortality at 28 days in patients with sepsis, which is of significant clinical importance and deserves further study.

Liquid Template Assisted Activation for "Egg Puff"-Like Hard Carbon toward High Sodium Storage Performance.

The slow solid diffusion dynamics of sodium ions and the side-reaction of sodium metal plating at low potential in the hard carbon anode of sodium ion batteries (SIBs) pose significant challenges to the safety manipulation of high-rate batteries. Herein, a simple yet powerful fabricating method is reported on for "egg puff"-like hard carbon with few N doping using rosin as a precursor via liquid salt template-assisted and potassium hydroxide dual activation. The as-synthesized hard carbon delivers promising electrochemical properties in the ether-based electrolyte especially at high rates, based on the absorption mechanism of fast charge transfer. The optimized hard carbon exhibits a high specific capacity of 367 mAh g-1 at 0.05 A g-1 and 92.9% initial coulombic efficiency (ICE), 183 mAh g-1 at 10 A g-1 , and ultra-long cycle stability of reversible discharge capacity of 151 mAh g-1 after 12,000 cycles at 5 A g-1 with the average coulombic efficiency of ≈99% and the decay of 0.0026% per cycle. These studies will undoubtedly provide an effective and practical strategy for advanced hard carbon anode of SIBs based on adsorption mechanism.

Association of CDSS score and 60-day mortality in Chinese patients with non-APL acute myeloid leukemia: a retrospective cohort study.

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy, and is one of the triggers of DIC, the latter is an essential factor in the early death of patients with AML. However, the timely identification of DIC remains a challenge. The Chinese DIC Scoring System (CDSS) is a common consensus widely used in China; but, there are few reports on its application in patients with AML. We undertake this retrospective cohort study to investigate the association between CDSS score and 60-day mortality. CDSS scores were evaluated after admission. The outcome was all-cause 60-day mortality. Multivariate Cox regression analyses were performed to calculate the adjusted hazard ratio (HR) and the corresponding 95% confidence interval (CI). Survival curves were plotted by Kaplan-Meier and log-rank analyses. Subgroup analyses were stratified by relevant effect covariates. A total of 570 consecutive patients with primary AML were included. We found an association between a 39% increase in 60-day mortality and a 1 point increase in CDSS score (HR = 1.39, 95% CI 1.25-1.54), which was associated with a 189% increase in 60-day mortality in CDSS scores ≥ 6 compared with that in the CDSS scores < 6 (HR = 2.89, 95% CI 1.91-4.38). After adjusting for all potential con-founders, a 27% and a 198% increase were observed (HR = 1.27, 95% CI 1.01-1.61; HR = 2.98, 95% CI 1.24-7.19), respectively. There is association between 60-day mortality and CDSS score in patients with AML. These findings may help hematologists in making informed treatment decisions.

Association between Lactate Dehydrogenase and 30-Day Mortality in Patients with Sepsis: a Retrospective Cohort Study.

BACKGROUND: Sepsis is one of the major causes of death in intensive care unit patients, so it is urgent to explore indicators for rapid and effective screening of sepsis mortality risk. The purpose of this study is to explore the association of LDH level with 30-day mortality in sepsis patients to improve patient survival outcomes. METHODS: In this retrospective cohort study, a total of 5,275 patients with sepsis from the Medical Information Mart for Intensive Care IV (MIMIC-IV). LDH level at admission was obtained, and the outcome indicator was the 30-day mortality. Multivariate Cox regression and Kaplan-Meier survival curve analysis were used to assess the relationship between LDH level and 30-day mortality in patients with sepsis. RESULTS: A total of 5,275 patients with sepsis were screened, the 30-day mortality was 51.5%. In multivariate regression models, hazard ratio [HR] and 95% confidence interval [CI] for Log2 and LDH ≥ 250 UI/L were 1.33 (1.29 - 1.37) and 1.69 (1.54 - 1.85), respectively. Kaplan-Meier survival curve analysis suggested that LDH level is associated with prognosis in patients with sepsis. CONCLUSIONS: LDH level was associated with 30-day mortality, which can be used as an important predictor of clinical outcomes for patients.

Association between serum albumin and 60-day mortality in Chinese Hakka patients with non-APL acute myeloid leukemia: a retrospective cohort study.

BACKGROUND: Acute myeloid leukemia (AML) is the main type of adult leukemia, and 60-day mortality is a vital clinical problem that doctors have to face at the begin with treatment. Studies on the association between serum albumin and 60-day mortality from AML (non-APL) are limited. METHODS: In this retrospective cohort study, ALB was measured after admission in all patients diagnosed with primary AML from Affiliated Ganzhou Hospital of Nanchang University between January 2013 and May 2021. The outcome was all-cause, 60-day mortality. Multivariable Cox regression analyses were performed to calculate the adjusted hazard ratio (HR) and its corresponding 95% confidence interval (CI). RESULTS: This study included 394 primary AML patients. The overall 60-day mortality was 28.9% (114/394); it was 43.1% (56/130), 27.5% (36/131), and 16.5% (22/133) for ALB quantile1 (Q, < 34.5 g/L), quantile 2 (Q2, 34.5-38.5 g/L), and quantile 3 (Q3, ≥ 38.6 g/L), respectively (P = 0.001). After adjusting for potential confounders, we found an association between a 6% decrease in 60-day mortality rate and a 1 g/L increase in ALB level (HR = 0.94, 95% CI: 0.89-0.99, P = 0.015), which was associated with 38 and 70% decreases in 60-day mortality rates in Q2 (HR = 0.50, 95% CI: 0.30-0.86, P = 0.012) and Q3 (HR = 0.47, 95% CI: 0.2 5-0.90, P = 0.022), respectively, compared with that in Q1. Similar results were obtained after subgrouping based on an ALB level of 35 g/L (HR = 0.55, 95% CI: 0.34-0.88, P = 0.013). CONCLUSIONS: Serum albumin was significantly associated with 60-day mortality of primary AML, which has important clinical significance. Further investigation is warranted.

Megaloblastic Anemia Masked by an Unrecognized Hemoglobinopathy.

BACKGROUND: Deficiency of vitamin B(12) or folate causes megaloblastic anemia (MA). The disease presents with pancytopenia due to the excessive cellular apoptosis of hematopoietic progenitor. MA is characterized by the presence of high mean corpuscular volume in the blood routine test and hyperlobulation nuclei of the granulocytes in the peripheral blood smears, and megaloblasts in the bone marrow. METHODS: We report a rare case, in which megaloblastic anemia was masked by an unrecognized hemoglobinopathy and presented with normocytic anemia and atypical morphological features of bone marrow. RESULTS: The patient was finally diagnosed with coexistence of MA and a-thalassemia minor due to determination of folate deficiency and genetic mutation for a-thalassemia. CONCLUSIONS: The case focuses on the contribution of the peripheral circulating blood smear examination in the diagnosis of anemia.

Association between serum lactate dehydrogenase and 60-day mortality in Chinese Hakka patients with acute myeloid leukemia: A cohort study.

BACKGROUND: There is evidence that a high level of serum lactate dehydrogenase (LDH) is associated with poorer overall survival in acute myeloid leukemia (AML), but its link to 60-day mortality of AML remains unclear. METHODS: All patients newly diagnosed with AML were included in this cohort study. LDH was measured for the first time after admission. Multivariable logistic regression was used to explore the association between serum LDH and 60-day mortality. Interaction and stratified analyses were conducted including age, sex, albumin, glucose, myoglobin, and standard chemotherapy. RESULTS: Three hundred and seventy-one patients ≥15 years of age, who were newly diagnosed with AML, were consecutively selected. The total prevalence of 60-day mortality was 27.2% (101/371), while it was 32.1% (42/131) and higher than in the LDH ≥570U/L compared with the LDH<570U/L, with the prevalence of 24.6% (59/240); however, the difference was not statistically significant. In multivariate regression models, odd ratios and corresponding 95% confidence intervals (CIs) for Log2 and twice limit of normal (ULN) of LDH were 1.46 (1.0, 2.14) and 2.76 (1.24, 6.16), respectively. Interaction analysis revealed no interactive role in the association between LDH concentration and 60-day mortality. CONCLUSIONS: Serum LDH level was associated with 60-day mortality, especially for the patients with LDH ≥570U/L.

Nitrogen-doped porous carbon microspheres for high-rate anode material in lithium-ion batteries.

Developing high-capacity anode materials is urgent for next-generation lithium-ion batteries (LIBs) with the increasing need of larger scale applications. In order to obtain suitable anode materials, nitrogen-doped porous carbon microspheres (NPCMs) were prepared via spray drying followed by carbonization using chitosan as both carbon and nitrogen sources. The structure and properties of NPCMs were characterized by thermogravimetric, Raman spectroscopic, x-ray diffraction, scanning electron microscopic, transmission electron microscopic as well as x-ray photoelectron spectroscopic analysis, and the electrochemical performance of NPCM electrodes were also evaluated. The results show that the diameter of the obtained microspheres is 1-7 µm. When used as the anode material, the NPCMs display a reversible capacity of 443 mAh g-1 at 100 mA g-1 after 120 cycles and maintain a high capacity of 377 mAh g-1 at 1 A g-1 after 500 cycles. Even at a high current density of 4 A g-1, a discharge capacity of 256 mAh g-1 can also be obtained. The excellent rate performance and long cycle life of the electrode might be ascribed to the nitrogen-doping, porous and amorphous structure of NPCMs. The results suggest that the prepared NPCMs have the potential to be used as a promising anode material for high-capacity LIBs.

Hierarchically porous CuO spindle-like nanosheets grown on a carbon cloth for sensitive non-enzymatic glucose sensoring.

Herein, porous CuO spindle-like nanosheets were fabricated on a carbon cloth using a facile hydrothermal method, and surface morphology, microstructure, and glucose sensing performance were studied. The porous spindle-like nanosheets are constructed by nanoparticles and slit-like pores, exhibiting a hierarchical structure. When used for non-enzymatic glucose sensoring, the obtained CuO nanosheet electrode exhibits a wide linear range from 0.05 to 3.30 mM, a high sensitivity of 785.2 µA mM-1 cm-2 and a low detection limit of 0.22 µM (S/N = 3). Besides, good selectivity, stability, and reproducibility for glucose detection indicate a promising application of CuO nanosheet electrodes as non-enzymatic glucose sensors.

Co(OH)2 nanosheets decorated Cu(OH)2 nanorods for highly sensitive nonenzymatic detection of glucose.

Co(OH)2 nanosheets/Cu(OH)2 nanorods composite electrodes for non-enzymatic glucose detection were fabricated by electrodepositing Co(OH)2 nanosheets on Cu(OH)2 nanorods substrate grown directly on the copper sheet via a simple one-step reaction. The Co(OH)2 nanosheets/Cu(OH)2 nanorods composite electrode was characterized by scanning electron microscopy, energy dispersive x-ray spectroscopy, x-ray diffraction and x-ray photoelectron spectroscopy. The glucose sensing performance of the composite electrode was investigated by cyclic voltammetry and chronoamperometry. The composite electrode shows high sensitivity of 2366 µA mM-1 cm-2 up to 2 mM with a lower detection limit of 0.17 mM (S/N = 3). The composite electrode is highly selective to glucose in the presence of various substances that always co-exist with glucose in real blood samples. The response of the composite towards human blood serum was in good agreement with that of commercially available glucose sensors, suggesting that a promising electrode material for highly sensitive and selective non enzymatic detection of glucose can be envisioned.

Synergistic effect of uniform lattice cation/anion doping to improve structural and electrochemical performance stability for Li-rich cathode materials.

There has been extensive research into lithium-rich layered oxide materials as candidates for the nextgeneration of cathode materials in lithium-ion batteries, due to their high energy density and low cost; however, their poor cycle life and fast voltage fade hinder their large-scale commercial application. Here, we propose a novel cation/anion (Na+/PO4 3-) co-doping approach to mitigate the discharge capacity and voltage fade of a Co-free Li1.2Ni0.2Mn0.6O2 cathode. Our results show that the synergistic effect of cation/anion doping can promote long cycle stability and rate performance by inhibiting the phase transformation of the layered structure to a spinel or rock-salt structure and stabilizing the well-ordered crystal structure during long cycles. The co-doped sample exhibits an outstanding cycle stability (capacity retention of 86.7% after 150 cycles at 1 C) and excellent rate performance (153 mAh g-1 at 5 C). The large ionic radius of Na+ can expand the Li slab to accelerate Li diffusion and the large tetrahedral PO4 3- polyanions with high electronegativity stabilize the local structure to improve the electrochemical performance.

Biomimetic Mineralization of Magnetic Iron Oxide Nanoparticles Mediated by Bi-Functional Copolypeptides.

Magnetite (Fe3O4) nanoparticles are widely used in multiple biomedical applications due to their magnetic properties depending on the size, shape and organization of the crystals. However, the crystal growth and morphology of Fe3O4 nanoparticles remain difficult to control without using organic solvent or a high temperature. Inspired by the natural biomineralization process, a 14-mer bi-functional copolypeptide, leveraging the affinity of binding Fe3O4 together with targeting ovarian cancer cell A2780, was used as a template in the biomimetic mineralization of magnetite. Alongside this, a ginger extract was applied as an antioxidant and a size-conditioning agent of Fe3O4 crystals. As a result of the cooperative effects of the peptide and the ginger extract, the size and dispersibility of Fe3O4 were controlled based on the interaction of the amino acid and the ginger extract. Our study also demonstrated that the obtained particles with superparamagnetism could selectively be taken up by A2780 cells. In summary, the Fe3O4-QY-G nanoparticles may have potential applications in targeting tumor therapy or angiography.

Hierarchically Porous N,S-Codoped Carbon-Embedded Dual Phase MnO/MnS Nanoparticles for Efficient Lithium Ion Storage.

An intriguingly nanostructured composite comprising of MnO/MnS nanoparticles embedded in an N,S-codoped carbon frame (MnO/MnS@C) is designed here and employed as a promising Li-ion storage electrode material to address the challenge of inferior conductivity and large volume change toward manganese chalcogenide-based anode. Combining with the merits of coherent MnO/MnS, elaborately hierarchical-porous architecture and N,S-codoped carbon frame, this composite exhibits high lithium-ion storage capacity (591 mAh g-1 at 0.1 A g-1) and remarkable cyclic performance (628 mAh g-1 at 1 A g-1 over 330 cycles). It is revealed via quantitative analysis that capacitive effect is also responsible for Li+ storage except ordinary diffusion-controlled mechanism, which consists of faradaic surface pseudocapacitance rooting from further oxidation of Mn2+ and nonfaradaic interfacial double-layer capacitance stemming from the charge separation at the MnO/MnS phase boundary. As a dynamic equilibrium for diffusion-controlled lithium storage, such capacitive contribution leads to ever-increasing Li-ion storage. The delicate construction endows an improved ion/electron transport kinetics, increased electrode/electrolyte contact area and plentifully heterogeneous interface, accounting for the high capacity and long-cycle stability.

Will Chinese external therapy with compound Tripterygium wilfordii hook F gel safely control disease activity in patients with rheumatoid arthritis: design of a double-blinded randomized controlled trial.

BACKGROUND: Chinese external therapy (CET) is a topical application with mainly Chinese herb medicine therapy with thousands of years of historical implications and is a clinical routine that is commonly used for relieving joint-related symptoms in patients with arthritis in Chinese hospitals. However, there is a paucity of modern medical evidence to support its effectiveness and safety. Thus, we propose to implement a randomized, double-blinded, placebo-controlled clinical trial in patients with rheumatoid arthritis (RA) using, as the experimental intervention, topical application of a hospital-compounded gel preparation of Tripterygium wilfordii Hook F (TwHF). METHODS: This study will be an 8-week double-blinded, randomized, placebo-controlled clinical trial conducted at Guang'anmen Hospital in Beijing, China, and 168 patients with moderately active RA will be randomly assigned with a 1:1 ratio to apply a topical gel preparation containing TwHF or placebo. The primary outcome variable will be the proportion of subjects, by study group, to achieve a 20% improvement in the American College of Rheumatology criteria (ACR20) by week 8. Secondary outcome measures to be assessed at weeks 4 or 8 will include: measurement of ACR20 response rate at week 4, ACR50 response rate, the changes in DAS28 score, and joint synovitis classification assessment monitored by musculoskeletal ultrasound. Safety evaluations conducted at weeks 4, 8 and 12 will be based on spontaneous complaints by the study subjects, but special emphasis will be focused on cutaneous allergy and alterations of menstruation in premenopausal female participants. Statistical analyses will be performed using the intention to treat analysis data set. DISCUSSION: This proposed clinical trail is designed to evaluate the efficacy and safety of CET based on a single topically-applied agent in a relatively large patient population with RA. This study protocol gives a detailed description of the usage and dosage of the topical compound TwHF gel and the methodology of this study. In addition, it is hoped that the outcomes of this study will be viewed as supporting the generalizability of CET in the setting of inflammatory rheumatic diseases. The results of this study are expected to have important public health implications for Asian RA patients that currently utilize CET as a complimentary treatment. TRIAL REGISTRATION: Clinical trial gov Identifier: NCT02818361 . Registrated on Jun. 15, 2016.

Tumor-targeted paclitaxel-loaded folate conjugated poly(ethylene glycol)-poly(L-lactide) microparticles produced by supercritical fluid technology.

The new biodegradable diblock copolymers poly(ethylene glycol)-poly(L-lactide) (PEG-PLLA) were synthesized and were chemically conjugated with folate (FA) in the PEG terminal ends to form FA-PEG-PLLA. Then the hydrophobic drug paclitaxel (PTX) loaded microparticles (PTX/FA-PEG-PLLA) were produced via solution enhanced dispersion by supercritical fluids (SEDS). These microparticles exhibited sphere-like shape by scanning electron microscopy observation and showed narrow hydrodynamic size distributions by dynamic light scattering measurement. Drug loading of PTX loaded microparticles was about 7-9% and the encapsulation efficiency of PTX loaded microparticles was about 18-23%. Flow cytometry and confocal laser scanning microscope analyses revealed that fluorescein isothiocyanate labeled FA conjugated microparticles presented significantly higher cellular uptake than FA-free group due to the FA-receptor-mediated endocytosis. In vitro cytotoxicity evaluation indicated that FA-PEG-PLLA expressed negligible cytotoxicity to mouse fibroblasts L929 cells. Moreover, PTX/FA-PEG-PLLA microparticles exhibited much higher anti-cancer efficacy than PTX/PEG-PLLA microparticles against human ovarian cancer SKOV3 cells. Nude mice xenografted with SKOV3 cells were used in biodistribution studies, the results indicated that an increased amount of PTX was accumulated in the tumor tissue deal with PTX/FA-PEG-PLLA microparticles. These results collectively suggested that PTX/FA-PEG-PLLA microparticles prepared by SEDS would have potential in anti-tumor applications as a tumor-targeted drug delivery formulation.

Effects of combinations of BMP-2 with FGF-2 and/or VEGF on HUVECs angiogenesis in vitro and CAM angiogenesis in vivo.

Angiogenesis, a complex biologic process, is regulated by a large number of angiogenic factors, including vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). Whether Bone morphogenetic proteins-2 (BMP-2), the osteoinductive factor, could significantly reinforce the effect of VEGF and FGF-2 on angiogenesis has not been studied in detail. To study the positive effects of multiple growth factors on angiogenesis, HUVECs were treated with BMP-2, VEGF, or FGF-2 singly and in binary and ternary combinations. This study further investigates the optimal timing of the ternary combination of BMP-2, VEGF and FGF-2 for angiogenesis in the chorioallantoic membrane (FGF-2 CAM). Results of single applications of BMP-2, VEGF, or FGF-2 suggested that HUVECs angiogenesis could be promoted in a dose-dependent manner and that the optimal concentration of BMP, VEGF and FGF-2 was 10, 50 and 1 ng/mL, respectively. These results indicated that the angiogenic activity of VEGF and FGF-2 was amplified by combining with BMP-2. The ternary combination of BMP-2, VEGF and FGF-2 exhibited a positive and synergistic effect on HUVECs angiogenesis, with the lower concentrations of each factor (1 ng/mL of BMP-2, 25 ng/mL of VEGF and 0.1 ng/mL of FGF-2) being sufficient to show synergistic promotion. When VEGF and FGF-2 were added in the initial activation stage and BMP-2 was added in the maturation stage, both HUVECs angiogenesis in vitro and CAM angiogenesis in vivo could be enhanced more effectively. These results could provide a basis for the controlled release systems capable of delivering multiple factors sequentially to promote angiogenesis in tissue engineering.

Synergistic and sequential effects of BMP-2, bFGF and VEGF on osteogenic differentiation of rat osteoblasts.

In the present study, the effects of bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) on regulation of rat osteoblast (ROB) maturation in vitro were investigated. It was found that the proliferation, differentiation and mineralization of ROBs were all dose-dependently increased at particular times in the case of treatment with only one growth factor. To investigate the effects of combined treatment, ROBs were treated with either a single application of a relatively high dose of each growth factor, or binary/triple combined applications of relatively low doses of the growth factors. Osteogenic differentiation was significantly promoted in the triple combination treatment of BMP-2, VEGF and bFGF compared with the single or binary combination treatments. The optimal timing of the triple combination to enhance osteogenesis was also tested. When bFGF and VEGF were added in the early stage, and BMP-2 and VEGF were added in the late stage, osteogenic differentiation of ROBs could be enhanced more effectively. These results could be used to construct bone tissue engineering scaffolds that release growth factors sequentially.