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There has been a dramatic increase in the emergence of antibiotic-resistant bacterial strains, which has made antibiotic choices for infection control increasingly limited and more expensive. In the U.S. alone, antibiotic-resistant bacteria cause at least 2 million infections and 23,000 deaths a year resulting in a $55-70 billion per year economic impact. Antibiotics are critical to the success of surgical procedures including orthopedic prosthetic surgeries, and antibiotic resistance is occurring in nearly all bacteria that infect people, including the most common bacteria that cause orthopedic infections, such as Staphylococcus aureus (S. aureus). Most clinical cases of orthopedic surgeries have shown that patients infected with antibiotic-resistant bacteria, such as methicillin-resistant S. aureus (MRSA), are associated with increased morbidity and mortality. This paper reviews the severity of antibiotic resistance at the global scale, the consequences of antibiotic resistance, and the pathways bacteria used to develop antibiotic resistance. It highlights the opportunities and challenges in limiting antibiotic resistance through approaches like the development of novel, non-drug approaches to reduce bacteria functions related to orthopedic implant-associated infections. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:22-32, 2018.

Prevention of postsurgery infection and promotion of biointegration are the key factors to achieve long-term success in orthopedic implants. Localized delivery of antibiotics and bioactive molecules by the implant surface serves as a promising approach toward these goals. However, previously reported methods for surface functionalization of the titanium alloy implants to load bioactive ingredients suffer from time-consuming complex processes and lack of long-term stability. Here, we present the design and characterization of an adhesive, osteoconductive, and antimicrobial hydrogel coating for Ti implants. To form this multifunctional hydrogel, a photo-cross-linkable gelatin-based hydrogel was modified with catechol motifs to enhance adhesion to Ti surfaces and thus promote coating stability. To induce antimicrobial and osteoconductive properties, a short cationic antimicrobial peptide (AMP) and synthetic silicate nanoparticles (SNs) were introduced into the hydrogel formulation. The controlled release of AMP loaded in the hydrogel demonstrated excellent antimicrobial activity to prevent biofilm formation. Moreover, the addition of SNs to the hydrogel formulation enhanced osteogenesis when cultured with human mesenchymal stem cells, suggesting the potential to promote new bone formation in the surrounding tissues. Considering the unique features of our implant hydrogel coating, including high adhesion, antimicrobial capability, and the ability to induce osteogenesis, it is believed that our design provides a useful alternative method for bone implant surface modification and functionalization.

Sutures penetrate tissues to close wounds. This process leads to inflammatory responses, prolongs healing time, and increases operation complexity. It becomes even worse when sutures are applied to stress-sensitive and fragile tissues. By bonding tissues via forming covalent bonds, some medical adhesives are not convenient to be used by surgeons and have side effects to the tissues. Here egg albumen adhesive (EAA) is reported with ultrahigh adhesive strength to bond various types of materials and can be easily used without any chemical and physical modifications. Compared with several commercial medical glues, EAA exhibits stronger adhesive property on porcine skin, glass, polydimethylsiloxane. The EAA also shows exceptional underwater adhesive strength. Finally, wound closure using EAA on poly(caprolactone) nanofibrous sheet and general sutures is investigated and compared in a rat wound model. EAA also does not show strong long-term inflammatory response, suggesting that EAA has potential as a medical glue, considering its abundant source, simple fabrication process, inherent nontoxicity, and low cost.

There has been a dramatic increase in the emergence of antibiotic-resistant bacterial strains, which has made antibiotic choices for infection control increasingly limited and more expensive. In the U.S. alone, antibiotic-resistant bacteria cause at least 2 million infections and 23,000 deaths a year resulting in a $55-70 billion per year economic impact. Antibiotics are critical to the success of surgical procedures including orthopedic prosthetic surgeries, and antibiotic resistance is occurring in nearly all bacteria that infect people, including the most common bacteria that cause orthopedic infections, such as Staphylococcus aureus (S. aureus). Most clinical cases of orthopedic surgeries have shown that patients infected with antibiotic-resistant bacteria, such as methicillin-resistant S. aureus (MRSA), are associated with increased morbidity and mortality. This paper reviews the severity of antibiotic resistance at the global scale, the consequences of antibiotic resistance, and the pathways bacteria used to develop antibiotic resistance. It highlights the opportunities and challenges in limiting antibiotic resistance through approaches like the development of novel, non-drug approaches to reduce bacteria functions related to orthopedic implant-associated infections. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:22-32, 2018.

Biodegradable metals, including magnesium (Mg), iron (Fe) and zinc (Zn), have been proposed and developed for temporary implants with the expectation to degrade and be absorbed gradually in vivo during the tissue healing process. Compared to Mg alloys and Fe alloys, the standard electrode potential of Zn is between that of Mg and Fe, so its degradation rate has been proved to be more likely in line with the clinical demand. In addition, Zn is one of the essential trace elements in human body and plays essential roles in many enzymes and in cell metabolic activity, proliferation and differentiation. Therefore, the recent progress of Zn-based metallic biomaterials is reviewed in this chapter for the development of high-performance metallic biomaterials.

Brick tea skeletal fluorosis is still a public health issue in the north-western area of China. However its pathogenesis remains unknown. Our previous study reveals that the severity of skeletal fluorosis in Tibetans is more serious than that in Kazaks, although they have similar fluoride exposure, suggesting the onset of brick tea type skeletal fluorosis might be genetically influenced. Here we show that MMP-2 rs2287074 SNP (G/A), but not rs243865, was associated with Brick tea type fluorosis in Tibetans and Kazaks, China. The trend test reveals a decline in probability for skeletal fluorosis with increasing number of A alleles in Tibetans. After controlling potential confounders, AA genotype had about 80 percent lower probability of developing skeletal fluorosis than GG genotype in Tibetans (odds ratio = 0.174, 95% CI: 0.053, 0.575), and approximately 53 percent lower probability in Kazaks (odds ratio = 0.462, 95% CI: 0.214, 0.996). A meta-analysis shows that the AA genotype had approximately 63 percent lower odds (odds ratio = 0.373, 95% CI: 0.202, 0.689) compared with GG genotype within the two ethnicities. A significant correlation was also found between the genotype of MMP2 rs2287074 and skeletal fluorosis severity. Therefore, the A allele of MMP2 rs2287074 could be a protective factor for brick tea skeletal fluorosis.

Silver (Ag) has been known for its antimicrobial properties for centuries but has received renewed interest in recent years primarily due to the rise of antibiotic-resistance and the development of Ag nanoparticles (AgNPs). In orthopedics, multiple applications containing Ag are being developed including Ag dressings, Ag-coated prosthetic implants, and Ag-based bone cements. In this chapter, we review the antimicrobial mechanisms as well as the delivery and metabolic pathways of Ag and the primary uses of Ag and AgNPs in orthopedic applications, focusing on their antimicrobial activity, toxicity, and clinical uses.

The Ti22Al25Nb alloy was prepared by reactive sintering with element powders. The reactive sintering process was conducted by step reactive sintering in order to prevent loss of Al; thus, the process was performed at 903 K, holding 60 min and 20 MPa, and then increased to 1523 K for 120 min and 30 MPa, followed by furnace cooling. The O (orthorhombic Ti 2 AlNb) phase and B2 phase were obtained in the sintered Ti22Al25Nb alloy, and a few Ti 3 Al phases. Subsequently, the microstructures and phases of the sintered alloy were analyzed at two sintering stages. Moreover, the forming mechanism of O (orthorhombic Ti 2 AlNb) phase and reactive mechanism were analyzed. In view of examining the tensile property, the tensile tests were carried out from 1233 K to1313 K at an interval of 20 K. The tensile datum indicated that the elongations increased with the increasing temperature and decreasing strain rate; the tensile strength decreased with increasing temperature and decreasing strain rate. From the experimental results, the maximum elongation of the sintered alloys was up to 146% at 1313 K at1.04×10 −4 s −1 , and tensile strength was above 85 MPa.

The Li-ion battery represents one of the most important and most technically challenging components of electric vehicles. The cathode is one of the three key components (i.e., cathode, anode, and electrolyte) of the Li-ion battery and determines the battery quality. The demand for higher energy density, lower cost, and environmentally friendly batteries makes Li-rich layered oxides xLi2MnO3·(1 − x)LiMO2 (LR-NMC) among the most attractive candidates for future cathode materials. In this review, we discuss the state-of-the-art research activities related to LR-NMC materials, including their structures, mechanisms of high capacity and large voltage, challenges, and strategies that have been studied to improve their performances. Finally, we conclude with some personal perspectives for the future development of LR-NMC materials.

The CO2 capture properties of M2CO3 (M = Na, K)-promoted and CaCO3-promoted MgO sorbents are investigated by first-principles density functional theory complemented with lattice phonon calculations. The calculated thermodynamic properties indicate that by forming double salts (M2Mg(CO3)2 and CaMg(CO3)2), compared to pure MgO, the maximum allowable CO2 capture temperatures of the M2CO3- and CaCO3- modified MgO sorbents are shifted to higher temperature ranges. Under pre-combustion conditions with PCO2 = 10 bar, the Na2CO3-promoted and CaCO3-promoted MgO sorbents can capture CO2 at temperatures as high as 915 K and 740 K respectively. While under post-combustion conditions with PCO2 = 0.1 bar, their maximum allowable CO2 capture temperatures are 710 K and 600 K respectively. However, when adding K2CO3 into MgO, under both pre- and post-combustion conditions, its maximum CO2 capture temperatures only increased about 10 K relative to pure MgO. These results indicate that by mixing another solid into MgO, it is possible to shift its CO2 capture temperature to fit practical industrial needs.

Our current challenge in the management of prosthetic joint infection is the eradication of biofilms which has driven the need for improved antimicrobial agents and regimens. In this study, the antimicrobial peptide, LL-37, and silver nanoparticles (AgNPs) were investigated for their antimicrobial efficacies against Staphylococcus aureus (S. aureus), a microorganism commonly implicated in biofilm-related infections. These antimicrobials were compared to conventional antibiotics and combination treatments with rifampin. Using a Centers for Disease Control reactor, 24 h S. aureus biofilms were formed on cobalt-chromium discs and the anti-biofilm activity was determined by quantifying the amount of colony forming units following treatments. We found that LL-37 was the most efficacious antimicrobial agent with a more than 4 log reduction in colony counts. In comparison, silver nanoparticles and conventional antibiotics were not as efficacious, with a less than 1 log reduction in colony counts. Antimicrobial combination treatments with rifampin significantly increased the log reduction for AgNPs and gentamicin, although still significantly less than LL-37 in isolation. Furthermore, kinetic studies revealed the rapid elimination of S. aureus biofilm with LL-37. Collectively, the results of this study demonstrated that LL-37 was an effective agent against S. aureus biofilms and may have potential clinical applications in the eradication of biofilms and treatment of prosthetic joint infection.

Correction for ‘Hydrogels from natural egg white with extraordinary stretchability, direct-writing 3D printability and self-healing for fabrication of electronic sensors and actuators’ by Qiang Chang et al., J. Mater. Chem. A, 2019, DOI: 10.1039/c9ta06233e.

Encapsulating living cells within multilayer functional shells is a crucial extension of cellular functions and a further development of cell surface engineering. In the last decade, cell encapsulation has been widely utilized in many cutting-edge biomedical fields. Compared with other techniques for cell encapsulation, layer-by-layer (LbL) self-assembly technology, due to the versatility and tunability to fabricate diverse multilayer shells with controllable compositions and structures, is considered as a promising approach for cell encapsulation. This review summarizes the state-of-the-art and potential future biomedical applications of LbL cell encapsulation. First of all, a brief introduction to the LbL self-assembly technique, including assembly mechanisms and technologies, is made. Next, different cell encapsulation strategies by LbL self-assembly techniques are explained. Then, the biomedical applications of LbL cell encapsulation in cell-based biosensors, cell transplantation, cell/molecule delivery, and tissue engineering, are highlighted. Finally, discussions on the current limitations and future perspectives of LbL cell encapsulation are also provided.

For the first time, amino acid (AA) and AA-complex based solid sorbents for CO 2 removal were investigated by immobilizing AAs and AA-complexes into porous polymethylmethacrylate (PMMA) microspheres. Deposition of pure AAs into porous PMMA supports led to limited CO 2 adsorption in sorbents, because large AA particles or crystals were formed during deposition of pure AAs into PMMA microspheres and some pores of the PMMA microspheres were clogged. Among the AA sorbents studied, Arginine (Arg) solid sorbents had the highest CO 2 adsorption capacity. Interestingly, by forming AA-complexes with other polymers, we substantially improved AA water solubility, achieved uniform immobilization of AAs inside PMMA microspheres, and obtained high CO 2 adsorption capacity. We found that the types of AA-complexes, complex loading capacity, and ratio of AAs in the complexes could have significant effects on CO 2 adsorption properties. Especially, complexing Arg with a strong polyelectrolyte (i.e. polystyrene sulfonate) resulted in substantially improved AA water solubility and high CO 2 adsorption capacity. Our developed AA-complex based solid sorbents could be innovative since they could eliminate concerns related to potential equipment corrosion as well as high heat duty associated with aqueous solvent regeneration all the while retaining the advantageous properties (high thermal stability, excellent biocompatibility, and negligible volatility) of AAs.

Ovarian cancer is the fifth leading cause of cancer deaths for women in America. With no known carcinogens or manageable risk factors, targeted prevention is currently unavailable. Angioprevention is a nonspecific strategy to limit the growth of solid tumors and is especially suitable for ovarian cancers. In search of angiopreventive agents, we examined chaetoglobosin K (ChK), a natural cytochalasan compound from the fungus Diplodia macrospora. We found that ChK significantly inhibits cell viability at concentrations as low as 0.5 μmol/l for A2780/CP70 ovarian cancer cells and 1.0 μmol/l for OVCAR-3 cells. ChK also significantly inhibits the secretion of key angiogenesis mediators, including Akt (which is also known as protein kinase B), hypoxia-inducible factor 1α (HIF-1α), and vascular epithelial growth factor (VEGF) by ovarian cancer cells. More importantly, ChK inhibits in-vitro and in-vivo angiogenesis induced by ovarian cancer cells and reduces the migratory capability of human umbilical vein endothelial cells. Through transfection of HIF-1α plasmids in luciferase assays, we found that ChK executes its VEGF inhibition by mediating the downregulation of HIF-1α. Furthermore, chromatin immunoprecipitation assays using the HIF-1α antibody revealed that ChK inhibits the interaction of HIF-1α with the VEGF promoter. Through transfection of Akt plasmids, we found that inhibition of HIF-1α by ChK occurs through downregulation of Akt. To our knowledge, this is the first report about the potential angioprevention of ChK. Our data suggest that this natural fungal bioactive compound effectively inhibits angiogenesis through downregulation of VEGF-binding HIF-1α and could be an effective agent for cancer treatment.

Chronic and recurrent bone infections occur frequently but have not been explained. Staphylococcus aureus (S. aureus) is often found among chronic and recurrent infections and may be responsible for such infections. One possible reason is that S. aureus can internalize and survive within host cells and by doing so, S. aureus can evade both host defense mechanisms and most conventional antibiotic treatments. In this study, we hypothesized that intra-cellular S. aureus could induce infections in vivo. Osteoblasts were infected with S. aureus and, after eliminating extra-cellular S. aureus, inoculated into an open fracture rat model. Bacterial cultures and radiographic observations at post-operative day 21 confirmed local bone infections in animals inoculated with intra-cellular S. aureus within osteoblasts alone. We present direct in vivo evidence that intra-cellular S. aureus could be sufficient to induce bone infection in animals; we found that intra-cellular S. aureus inoculation of as low as 102 colony forming units could induce severe bone infections. Our data may suggest that intra-cellular S. aureus can "hide" in host cells during symptom-free periods and, under certain conditions, they may escape and lead to infection recurrence. Intra-cellular S. aureus therefore could play an important role in the pathogenesis of S. aureus infections, especially those chronic and recurrent infections in which disease episodes may be separated by weeks, months, or even years.

Biomimetic nanofibrous scaffolds mimicking important features of the native extracellular matrix provide a promising strategy to restore functions or achieve favorable responses for tissue regeneration. This review provides a brief overview of current state-of-the-art research designing and using biomimetic electrospun nanofibers as scaffolds for tissue engineering. It begins with a brief introduction of electrospinning and nanofibers, with a focus on issues related to the biomimetic design aspects. The review next focuses on several typical biomimetic nanofibrous structures (e.g. aligned, aligned to random, spiral, tubular, and sheath membrane) that have great potential for tissue engineering scaffolds, and describes their fabrication, advantages, and applications in tissue engineering. The review concludes with perspectives on challenges and future directions for design, fabrication, and utilization of scaffolds based on electrospun nanofibers.

The increasing resistance of bacteria to conventional antibiotics and the challenges posed by intracellular bacteria, which may be responsible for chronic and recurrent infections, have driven the need for advanced antimicrobial drugs for effective elimination of both extra- and intracellular pathogens. The purpose of this study was to determine the killing efficacy of cationic antimicrobial peptide LL-37 compared to conventional antibiotics against extra- and intracellular Staphylococcus aureus . Bacterial killing assays and an infection model of osteoblasts and S. aureus were studied to determine the bacterial killing efficacy of LL-37 and conventional antibiotics against extra- and intracellular S. aureus . We found that LL-37 was effective in killing extracellular S. aureus at nanomolar concentrations, while lactoferricin B was effective at micromolar concentrations and doxycycline and cefazolin at millimolar concentrations. LL-37 was surprisingly more effective in killing the clinical strain than in killing an ATCC strain of S. aureus . Moreover, LL-37 was superior to conventional antibiotics in eliminating intracellular S. aureus . The kinetic studies further revealed that LL-37 was fast in eliminating both extra- and intracellular S. aureus . Therefore, LL-37 was shown to be very potent and prompt in eliminating both extra- and intracellular S. aureus and was more effective in killing extra- and intracellular S. aureus than commonly used conventional antibiotics. LL-37 could potentially be used to treat chronic and recurrent infections due to its effectiveness in eliminating not only extracellular but also intracellular pathogens.

Carbon dioxide (CO2) emissions are believed to be a major contributor to global warming. As a consequence, large anthropogenic CO2 sources worldwide will eventually be required to implement CO2 capture and storage technologies to control CO2 emissions. In order to guide the establishment of policies for CO2 removal, we reviewed the current status of CO2 capture patents and technologies based on the Espacenet patent database and found that more than 1000 patents have been published on sorbent, solvent, and membrane. More than 60% of these patents were published since the year 2000, and a sharp increase in patent numbers was seen in the last several years; ∼25% patents were published in the last 2 years. Substantially more patents on CO2 removal and separation technologies are expected in the coming years. Meanwhile, the top four major types of patents, which consist of more than 2/3 of these patents, were patents granted by Japan (JP), United States (US), World Intellectual Property Organization (WO), and China (CN), and approximately half of the patents were JP and US patents. Unfortunately, no current technologies for removing CO2 from large sources like coal-based power plants exist which satisfy the needs of safety, efficiency, and economy; further enhancement and innovation are much needed.

In this study, the relationships between high water fluoride exposure and essential hypertension as well as plasma ET-1 levels were investigated. A total of 487 residents aged 40 to 75 were randomly recruited from eight villages in Zhaozhou County from Heilongjiang Province in China and were divided into 4 groups according to the concentrations of fluoride in their water. Consumption levels of drinking water fluoride for normal, mild, moderate, and high exposure groups were 0.84±0.26 mg/L, 1.55±0.22 mg/L, 2.49±0.30 mg/L, and 4.06±1.15 mg/L, respectively. The prevalence of hypertension in each group was 20.16%, 24.54%, 32.30%, and 49.23%, respectively. There were significant differences between all the groups; namely, with the increase in water fluoride concentrations, the risk of essential hypertension in adults grows in a concentration-dependent manner. Significant differences were observed in the plasma ET-1 levels between the different groups (P

Objective: To explore the mechanisms underlying endothelin-1 (ET-1) elevations induced by excessive fluoride exposure. Methods: We measured serum and bone fluoride ion content and plasma ET-1 levels and compared these parameters among different groups in an animal model. We also observed morphological changes in the aorta and endothelium of rabbits. In cell experiments, human umbilical vein endothelial cells (HUVECs) were treated with varying concentrations of NaF for 24h, with or without 10 µM U0126 pretreatment for 1 h. ET-1 levels in culture fluid and intracellular reactive oxygen species (ROS) levels, as well as ET1 gene, endothelin-converting enzyme-1 (ECE-1), extracellular signal-regulating kinase 1/2 (ERK1/2), pERK1/2 expression levels and RAS activation were measured and compared among the groups. Results: Plasma ET-1 levels of rabbits increased significantly in fluorinated groups compared with those in the control group. The rabbit thoracic aortas became slightly hardened in fluorinated groups compared with those in the control group, and some vacuoles were present in the endothelial cell cytoplasm of the rabbits in fluorinated groups. In our cell experiments, ET1 gene and ECE-1 expression levels in HUVECs and ET-1 expression levels in the cell culture supernatants increased significantly in some experimental groups compared with those in the control group. These trends paralleled the changes in intracellular ROS levels, RAS activation, and the pERK1/2-to-ERK1/2 ratio. After U0126 was added, ECE-1 expression and ET-1 levels decreased significantly. Conclusion: Excessive fluoride exposure leads to characteristic endothelial damage (vacuoles), thoracic aorta hardening, and plasma ET-1 level elevations in rabbits. In addition, the ROS-RAS-MEK1/2-pERK1/2/ERK1/2 pathway plays a crucial—and at least partial—role in ET-1 over-expression, which is promoted by excessive fluoride exposure.

Uninterruptible Power Supply (UPS) is widely utilized to provide stable and high quality electricity for varying loads. Moreover, it is a critical means to maintain the voltage level of a microgrid with low-inertia. The control performance of UPS system directly affects the reliability and electricity quality of a microgrid. A large voltage deviation could result in component failure or even grid shutdown. In this paper, an adaptive performance-guaranteed controller is proposed for UPS integrated microgrid suffering from unknown parameters and nonlinear loads. A constrained state-space model of the plant is firstly developed and transformed into an equivalent unconstrained one via an error transformation technique. An adaptive controller is subsequently designed for the transformed system by using backstepping scheme. By this means, the bus voltage can be guaranteed to stay within arbitrarily user-defined bounds. Furthermore, all signals within the closed-loop system are proved to be bounded thru Lyapunov synthesis. Finally, the feasibility of the theoretical results is demonstrated via extensive simulation and experimental studies.

This paper describes preparation of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) mediated oxidized cellulose nanofibers (TOCNs) from corn husk. The process adopted for this work included alkaline treatment, TEMPO/NaBr/NaClO-mediated oxidation, and homogenization. The morphological investigation of TOCNs was performed using atomic force microscopy (AFM) and transmission electron microscopy (TEM). The chemical composition and structure of the material obtained after each stage of the treatments was characterized through Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis. The thermal stability of the samples was investigated by thermogravimetric analysis (TGA). The obtained TOCNs possessed a narrow width, ranging from 8 to 10 nm, and a high aspect ratio (> 300). The crystallinity type of TOCNs was found to be cellulose-Iβ. Compared with the original fibers, the crystallinity of TOCNs gradually increased because of the removal of hemicellulose and lignin, while the thermal stability decreased.

Haitao Luo,1 Bingbing Jiang,2 Bingyun Li,2–4 Zhaoliang Li,1 Bing-Hua Jiang,5 Yi Charlie Chen11Department of Biology, Natural Science Division, Alderson-Broaddus College, Philippi, 2Department of Orthopaedics, School of Medicine, West Virginia University, 3WVNano Initiative, 4Mary Babb Randolph Cancer Center, Morgantown, WV, USA; 5Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USAAbstract: Ovarian cancer is one of the leading causes of cancer death for women throughout the Western world. Kaempferol, a natural flavonoid, has shown promise in the chemoprevention of ovarian cancer. A common concern about using dietary supplements for chemoprevention is their bioavailability. Nanoparticles have shown promise in increasing the bioavailability of some chemicals. Here we developed five different types of nanoparticles incorporating kaempferol and tested their efficacy in the inhibition of viability of cancerous and normal ovarian cells. We found that positively charged nanoparticle formulations did not lead to a significant reduction in cancer cell viability, whereas nonionic polymeric nanoparticles resulted in enhanced reduction of cancer cell viability. Among the nonionic polymeric nanoparticles, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) nanoparticles incorporating kaempferol led to significant reduction in cell viability of both cancerous and normal cells. Poly(DL-lactic acid-co-glycolic acid) (PLGA) nanoparticles incorporating kaempferol resulted in enhanced reduction of cancer cell viability together with no significant reduction in cell viability of normal cells compared with kaempferol alone. Therefore, both PEO-PPO-PEO and PLGA nanoparticle formulations were effective in reducing cancer cell viability, while PLGA nanoparticles incorporating kaempferol had selective toxicity against cancer cells and normal cells. A PLGA nanoparticle formulation could be advantageous in the prevention and treatment of ovarian cancers. On the other hand, PEO-PPO-PEO nanoparticles incorporating kaempferol were more effective inhibitors of cancer cells, but they also significantly reduced the viability of normal cells. PEO-PPO-PEO nanoparticles incorporating kaempferol may be suitable as a cancer-targeting strategy, which could limit the effects of the nanoparticles on normal cells while retaining their potency against cancer cells. We have identified two nanoparticle formulations incorporating kaempferol that may lead to breakthroughs in cancer treatment. Both PEO-PPO-PEO and PLGA nanoparticle formulations had superior effects compared with kaempferol alone in reducing cancer cell viability.Keywords: nanochemoprevention, kaempferol, ovarian cancer, nanoparticles, viability, natural compound

By combining density functional theory and lattice phonon dynamics, the thermodynamic properties of CO2 absorption/desorption reactions with dehydrated potassium carbonates through K2CO3·1.5H2O + CO2 = 2KHCO3 + 0.5H2O(g) are analyzed. The energy change and the chemical potential of this reaction have been calculated and used to evaluate its thermodynamic properties and phase transitions. The results indicate that the K2CO3·1.5H2O can only be applied for postcombustion CO2 capture technology at temperatures lower than its phase transition temperature, which depends on the CO2 pressure and the steam pressure with the best range being PH2O ≤ 1.0 bar. Above the phase transition temperature, the sorbent will be regenerated into anhydrous K2CO3. If the steam pressure PH2O is much greater than 1.0 bar, it is possible to use the K2CO3·1.5H2O sorbent for precombustion CO2 capture technology. Compared to anhydrous K2CO3, K2CO3·1.5H2O requires less energy for regeneration.

Over the past two decades, fluoride effects on osteoclasts have been evaluated; however, its molecular mechanisms remain unclear. In this study, we investigated the effect of fluoride on osteoclast formation, function, and regulation using osteoclasts formed from mice bone marrow macrophages treated with the receptor activator of NF-κB ligand and macrophage colony-stimulating factor. Our data showed that fluoride levels ≤ 8 mg/L had no effect on osteoclast formation; however, it significantly reduced osteoclast resorption at 0.5 mg/L. Fluoride activity on bone resorption occurred through the inhibition of nuclear factor of active T cells (NFAT) c1 expression. Furthermore, the expression of its downstream genes, including the dendritic cell-specific transmembrane protein, c-Src, the d2 isoform of vacuolar (H+) ATPase v0 domain, matrix metalloproteinase 9, and cathepsin K were decreased, leading to impaired osteoclast acidification, reduced secretion of proteolytic enzymes, and decreased bone resorption. In summary, our results suggested that fluoride has different roles in osteoclast formation and function. Fluoride ≤ 8 mg/L did not impact osteoclast formation; however, it significantly decreased the resorption activity of newly formed osteoclasts. The molecular mechanism of fluoride action may involve inhibition of NFATc1 and its downstream genes.

The emission of fossil fuel carbon dioxide (CO{sub 2) to the atmosphere is implicated as the predominant cause of global climate change; therefore, advanced CO{sub 2} capture technologies are of the utmost importance. In this study, innovative amine-multilayered sorbents were fabricated using layer-by-layer (LbL) nanoassembly technology via alternate deposition of a CO{sub 2}-adsorbing amine polymer (e.g. polyethylenimine or PEI) and an oppositely-charged polymer (e.g. polystyrene sulfonate or PSS). We found that the developed sorbents could be used for CO{sub 2} capture and that LbL nanoassembly allows us to engineer their CO{sub 2} capture performance through the fabrication variables (e.g. deposition polymers, deposition media, and number of bilayers). PEI/PSS was found to be the best polymer combination for developing sorbents with relatively high CO{sub 2} capture capacity. The amine-multilayered solid sorbents possessed fine microstructures and may have similar polymer deposition within and on the surface of solid sorbents. These amine-multilayered sorbents had much faster CO{sub 2} desorption rates compared to sorbents prepared using the current PEI-impregnation approach. Such fast CO{sub 2} desorption could make sorbents a good option for CO{sub 2} removal from power plants and even the atmosphere.

The increasing clinical incidence and host risk of open fracture-associated infections, as well as the reduced effectiveness of conventional antibiotics to treat such infections, have driven the development of new therapies for the prophylaxis of open fracture-associated infections. We investigated percutaneous supplementation of a natural cytokine (i.e., interleukin 12p70 or IL-12) at an open fracture site to reduce open fracture-associated infections. We also determined the efficacy of the combination therapy of IL-12 and conventional antibiotic therapy in the prophylaxis of open fracture-associated infections. An open femur fracture infection model was produced by direct inoculation of a clinical isolate of Staphylococcus aureus after creating a femur fracture using rats. The animals were assigned to one of four groups: no drug administration, percutaneous supplementation of IL-12, intraperitoneal administration of the antibiotic ampicillin, or percutaneous IL-12 in combination with intraperitoneal ampicillin. Animals were euthanized at postoperative days 6, 10, 14, and 21. Percutaneous IL-12 led to a reduction in infection at postoperative days 6 and 10. For the first time, exogenous IL-12 was found to have additive effects in the prevention of infection when combined with conventional treatment (i.e., antibiotic therapy). Combination therapy of ampicillin and IL-12 substantially reduced the infection rate at postoperative day 6 and also decreased the time needed for complete inhibition of infection. Therefore, exogenous IL-12, providing a mechanism of protection independent of antibiotic resistance, complements the routine use of antibiotics.

In the literature, a few biological cells have been used as templates to form microcapsules of a variety of shapes and sizes. In this study, we proved the concept that living cells like platelets can be encapsulated with polyelectrolytes using electrostatic layer-by-layer self-assembly (LBL), and, most importantly, the encapsulation process did not induce activation of the platelets. Glycol-chitosan and poly-L-glutamic acid were electrostatically deposited onto platelets, and the encapsulation was confirmed using confocal laser scanning microscopy and scanning electron microscopy. Transmission electron microscopy observation further confirmed that the encapsulation process was mild and the activation of platelets was negligible. The encapsulation of living biological cells like platelets can serve as a model system in a wide range of biomedical applications including local and sustained drug delivery, immune protection of artificial tissues, and versatile artificial blood.

The current state-of-the-art for drug-carrying biomedical devices is mostly limited to those that release a single drug. Yet there are many situations in which more than one therapeutic agent is needed. Also, most polyelectrolyte multilayer films intended for drug delivery are loaded with active molecules only during multilayer film preparation. In this paper, we present the integration of capsules as vehicles within polypeptide multilayer films for sustained release of multiple oppositely charged drug molecules using layer-by-layer nanoassembly technology. Calcium carbonate (CaCO(3)) particles were impregnated with polyelectrolytes, shelled with polyelectrolyte multilayers, and then assembled onto polypeptide multilayer films using glutaraldehyde. Capsule-integrated polypeptide multilayer films were obtained after decomposition of CaCO(3) templates. Two oppositely charged drugs were loaded into capsules within polypeptide multilayer films postpreparation based on electrostatic interactions between the drugs and the polyelectrolytes impregnated within capsules. We determined that the developed innovative capsule-integrated polypeptide multilayer films could be used to load multiple drugs of very different properties (e.g., opposite charges) any time postpreparation (e.g., minutes before surgical implantation inside an operating room), and such capsule-integrated films allowed simultaneous delivery of two oppositely charged drug molecules and a sustained (up to two weeks or longer) and sequential release was achieved.

Interleukin 12 (termed IL-12p70 and commonly designated IL-12) is an important immunoregulatory cytokine that is produced mainly by antigen-presenting cells. The expression of IL-12 during infection regulates innate responses and determines the type of adaptive immune responses. IL-12 induces interferon-gamma (IFN-gamma) production and triggers CD4(+) T cells to differentiate into type 1 T helper (Th1) cells. Studies have suggested that IL-12 could play a vital role in treating many diseases, such as viral and bacterial infections and cancers. The unique heterodimeric structure, which IL-12 shares with its family members including IL-23, IL-27, and IL-35, has recently brought more attention to understanding the mechanisms that regulate the functions of IL-12. This article describes the structure and biological activities of IL-12 in both the innate and adaptive arms of the immune system, and discusses the applications of IL-12 in treating and preventing infections.

Implant-associated infection is a serious complication in orthopedic surgery, and endowing implant surfaces with antibacterial properties could be one of the most promising approaches for preventing such infection. In this study, we developed cefazolin loaded biodegradable polypeptide multilayer nanofilms on orthopedic implants. We found that the amount of cefazolin released could be tuned. A high local concentration of cefazolin was achieved within the first a few hours and therefore may inhibit bacterial colonization in the critical postimplantation period. The developed cefazolin loaded nanofilms showed their in vitro efficacy against Staphylococcus aureus; the more antibiotics loaded, the longer the nanocoated implant had antibacterial properties. More interestingly, antibiotic-loaded polypeptide multilayer nanofilms also improved osteoblast bioactivity including cell viability and proliferation. These findings suggested that biodegradable polypeptide multilayer nanofilms as antibiotic carriers at the implant/tissue interface are compatible with human cells such as osteoblasts and bactericidal to bacteria such as S. aureus. These characteristics could be promising for preventing implant-associated infection and potentially improving bone healing.

The increasing incidence of bacterial infection and the appearance of Staphylococcus aureus (S. aureus) strains that are resistant to commonly used antibiotics has made it important to develop non-antibiotic approaches for infection prevention. The aim of this study was to develop local monocyte chemoattractant protein-1 (MCP-1) and interleukin-12 p70 (IL-12 p70) therapies to prevent S. aureus infection by enhancing the recruitment and activation of macrophages, which are believed to play an important role in infection prevention as the first line of defense against invading pathogens. Nanocoating systems for MCP-1 and IL-12 p70 deliveries were prepared, and their release characteristics desirable for infection prevention in open fractures were explored. Local MCP-1 therapy reduced S. aureus infection and influenced white blood cell populations, and local IL-12 p70 treatment had a more profound effect on preventing S. aureus infection. No synergistic relationship in decreasing S. aureus infection was observed when MCP-1 and IL-12 p70 treatments were combined. This reported new approach may reduce antibiotic use and antibiotic resistance. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:48–54, 2010

Microcapsules made of biopolymers are of both scientific and technological interest and have many potential applications in medicine, including their use as controlled drug delivery devices. The present study makes use of the electrostatic interaction between polycations and polyanions to form a multilayered microcapsule shell and also to control the loading and release of charged drug molecules inside the microcapsule. Micron-sized calcium carbonate (CaCO3) particles were synthesized and integrated with chondroitin sulfate (CS) through a reaction between sodium carbonate and calcium nitrate tetrahydrate solutions suspended with CS macromolecules. Oppositely charged biopolymers were alternately deposited onto the synthesized particles using electrostatic layer-by-layer self-assembly, and glutaraldehyde was introduced to cross-link the multilayered shell structure. Microcapsules integrated with CS inside the multilayered shells were obtained after decomposition of the CaCO3 templates. The integration of a matrix (i.e., CS) permitted the subsequent selective control of drug loading and release. The CS-integrated microcapsules were loaded with a model drug, bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA), and it was shown that pH was an effective means of controlling the loading and release of FITC-BSA. Such CS-integrated microcapsules may be used for controlled localized drug delivery as biodegradable devices, which have advantages in reducing systemic side effects and increasing drug efficacy.

Implantation of dental and orthopaedic devices is affected by delayed or weak implant-bone integration and inadequate new bone formation. Innovative approaches have been sought to enhance implant-bone interaction to achieve rapid osseointegration. The aim of this study was to develop biomimetic polypeptide nanocoatings and to evaluate cell adhesion, proliferation, morphology, and biocompatibility of polypeptide nanocoatings on implant surfaces. A recently developed nanotechnology, i.e., electrostatic self-assembly, was applied to build polypeptide nanocoatings on implant models, i.e., stainless steel discs. Our in vitro tests using human osteoblast cells revealed that substantially more (one order magnitude higher) osteoblast cells were attached to polypeptide-coated, stainless steel discs than to uncoated discs within the first few hours of contact. The developed biomimetic nanocoatings may have great potential for dental and orthopaedic applications.

Residents living in fluorosis areas generally experienced long-term exposure to excessive fluoride in drinking water. The adverse effects of high fluoride levels on the nervous system have been studied; however, the effect of fluoride exposure on cognitive functions of elderly people in fluorosis areas is rarely reported. This study was aimed to find out the potential risk factors of cognitive impairment among elderly people who lived in fluorosis areas of China. A total of 511 subjects, aged 60 years or above, were investigated in fluorosis areas of Heilongjiang Province, Inner Mongolia Autonomous Region, Qinghai Province, and Xinjiang Uygur Autonomous Region. The Mini-Mental State Examination (MMSE) was used to examine cognitive functions of the study subjects. Based on the MMSE scores, the study subjects were divided into normal group and cognitive impairment group that consisted of mild, moderate, and severe groups. Multivariable logistic regression showed that a higher risk of cognitive impairment was associated with increased age and decreased education levels. Multiple linear regression analysis revealed that MMSE scores were negatively associated with serum homocysteine (Hcy) levels. However, both urinary fluoride and serum Hcy levels in the normal group were not the lowest among the four groups. Spearman's correlation analysis showed that urinary fluoride levels were positively correlated with serum Hcy (r s = 0.209, P

Background Brick tea type fluorosis is a public health concern in the north-west area of China. The association between SNPs of genes influencing bone mass and fluorosis has attracted attention, but the association of SNPs with the risk of brick-tea type of fluorosis has not been reported. Objective To investigate the modifying roles of GSTP1 rs1695 polymorphisms on this association. Methods A cross-sectional study was conducted. Brick-tea water was tested by the standard of GB1996-2005 (China). Urinary fluoride was tested by the standard of WS/T 89-2006 (China). Skeletal fluorosis was diagnosed by X-ray, the part we scheduled was forearm, shank, and pelvic, then diagnosed the skeletal fluorosis by the standard of WS/192-2008 (China). Gene polymorphism was tested by Sequenom MassARRAY system. Result The prevalence rate in different ethnical participants was different: Tibetan individuals had the highest prevalence rate of skeletal fluorosis. There were significant differences in genotype frequencies of GSTP1 Rs1695 among different ethnical participants (p

The electronic structural and phonon properties of Na2-αMαZrO3 (M ¼ Li,K, α = ¼ 0.0,0.5,1.0,1.5,2.0) are investigated by first-principles density-functional theory and phonon dynamics. The thermodynamic properties of CO2 absorption and desorption in these materials are also analyzed. With increasing doping level α, the binding energies of Na2-αLiαZrO3 are increased while the binding energies of Na2-α KαZrO3 are decreased to destabilize the structures. The calculated band structures and density of states also show that, at the same doping level, the doping sites play a significant role in the electronic properties. The phonon dispersion results show that few soft modes are found in several doped configurations, which indicates that these structures are less stable than other configurations with different doping levels. From the calculated relationships among the chemical-potential change, the CO2 pressure, and the temperature of the CO2 capture reactions by Na2-αMαZrO3, and from thermogravimetric-analysis experimental measurements, the Li- and K-doped mixtures Na2-αMαZrO3 have lower turnover temperatures (Tt) and higher CO2 capture capacities, compared to pure Na2ZrO3. The Li-doped systems have a larger Tt decrease than the K-doped systems. When increasing the Li-doping level α, the Tt of the corresponding mixture Na2-αLiαZrO3 decreases further to a low-temperature range. However, in themore » case of K-doped systems Na2-αKαZrO3, although doping K into Na2ZrO3 initially shifts its Tt to lower temperatures, further increases of the K-doping level α causes Tt to increase. Therefore, doping Li into Na2ZrO3 has a larger influence on its CO2 capture performance than the K-doped Na2ZrO3. Compared with pure solidsM2ZrO3, after doping with other elements, these doped systems’ CO2 capture performances are improved.« less

Powder mixtures of tungsten carbide and metallic cobalt (WC-Co) are widely used in various products. Nanoparticles are engineered structures with at least one dimension of 100 nm or smaller. WC-Co is known to be associated with lung injury and diseases. Angiogenesis is a key process during vasculature, carcinogenesis, recovery of injury, and inflammatory diseases. However, the cellular effects of WC-Co nanoparticles on angiogenesis remain to be elucidated. In this study, we investigated angiogenic response and relative mechanisms after exposure to WC-Co nanoparticles. Our results showed that WC-Co nanoparticles at 5 μg/cm(2) induced ROS production which activated AKT and ERK1/2 signaling pathways in lung epithelial cells by reactive oxygen species (ROS) staining and immunoblotting; WC-Co treatment also increased transcriptional activation of AP-1, NF-κB, and VEGF by reporter assay. Further studies demonstrated that ROS are upstream molecules of AKT and ERK signaling pathways; the activation of AP-1, NF-κB, and VEGF was through ROS generation, AKT and ERK1/2 activation. In addition, WC-Co nanoparticles affected the cells to induce angiogenesis by chicken chorioallantoic membrane (CAM) assay. These results illustrate that exposure to WC-Co nanoparticles induces angiogenic response by activating ROS, AKT, and ERK1/2 signaling pathways and the downstream molecules and elucidate the potential molecular mechanisms during this process. This information may be useful for preventing potential damage from nanoparticle exposure in the future.

Carbon dioxide (CO 2 ) is a major greenhouse gas responsible for global warming; hence, much effort has been attracted to developing new materials and technologies for CO 2 capture from process gas streams. Recently, phase-change solvents have emerged as one of the most promising approaches for CO 2 capture. During the phase-change process, an absorbent will typically form two phases (e.g., two liquid phases or liquid–solid phases) after CO 2 absorption. These two phases may be defined as CO 2 -rich and CO 2 -lean and can easily be separated from each other. The CO 2 -lean phase can be recycled back to the absorber and the CO 2 -rich phase can be sent to a stripper for regeneration. By regenerating only the CO 2 -rich phase, significant energy can be saved. In this chapter, we provide a comprehensive review of the state-of-the-art research activities related to phase-change solvents, including solvent design and characterization, and CO 2 capture performance and process design. After a brief introduction of conventional chemical absorption, several new solvents are discussed. Next, the state-of-the-art research activities related to phase-change solvents for CO 2 capture are highlighted. Our discussion concludes with some personal perspectives on future development in which phase-change solvents could be further studied.

Exposure to hard metal tungsten carbide cobalt (WC-Co) “dusts” in enclosed industrial environments is known to contribute to the development of hard metal lung disease and an increased risk for lung cancer. Currently, the influence of local and systemic inflammation on disease progression following WC-Co exposure remains unclear. To better understand the relationship between WC-Co nanoparticle (NP) exposure and its resultant effects, the acute local pulmonary and systemic inflammatory responses caused by WC-Co NPs were explored using an intra-tracheal instillation (IT) model and compared to those of CeO2 (another occupational hazard) NP exposure. Sprague-Dawley rats were given an IT dose (0-500 μg per rat) of WC-Co or CeO2 NPs. Following 24-hr exposure, broncho-alveolar lavage fluid and whole blood were collected and analyzed. A consistent lack of acute local pulmonary inflammation was observed in terms of the broncho-alveolar lavage fluid parameters examined (i.e. LDH, albumin, and macrophage activation) in animals exposed to WC-Co NP; however, significant acute pulmonary inflammation was observed in the CeO2 NP group. The lack of acute inflammation following WC-Co NP exposure contrasts with earlier in vivo reports regarding WC-Co toxicity in rats, illuminating the critical role of NP dose and exposure time and bringing into question the potential role of impurities in particle samples. Further, we demonstrated that WC-Co NP exposure does not induce acute systemic effects since no significant increase in circulating inflammatory cytokines were observed. Taken together, the results of this in vivo study illustrate the distinct differences in acute local pulmonary and systemic inflammatory responses to NPs composed of WC-Co and CeO2; therefore, it is important that the outcomes of pulmonary exposure to one type of NPs may not be implicitly extrapolated to other types of NPs.

The crosslinking of polymers in a polymeric material will alter the mechanical properties of the material. Control over the mechanical properties of polyelectrolyte multilayer films (PEMs) could be useful for applications of the technology in medicine and other areas. Disulfide bonds are 'natural' polypeptide crosslinks found widely in wild-type proteins. Here, we have designed and synthesized three pairs of oppositely charged 32mer polypeptide to have 0, 4, or 8 cysteine (Cys) residues per molecule, and we have characterized physical properties of the peptides in a PEM context. The average linear density of free thiol in the designed peptides was 0, 0.125, or 0.25 per amino acid residue. The peptides were used to make 10-bilayer PEMs by electrostatic layer-by-layer self-assembly (LBL). Cys was included in the peptides to study specific effects of disulfide bond formation on PEM properties. Features of film assembly have been found to depend on the amino acid sequence, as in protein folding. Following polypeptide self-assembly into multilayer films, Cys residues were disulfide-crosslinked under mild oxidizing conditions. The stability of the crosslinked films at acidic pH has been found to depend on the number of Cys residues per peptide for a given crosslinking procedure. Crosslinked and non-crosslinked films have been analysed by ultraviolet spectroscopy (UVS), ellipsometry, and atomic force microscopy (AFM) to characterize film assembly, surface morphology, and disassembly. A selective etching model of the disassembly process at acidic pH is proposed on the basis of the experimental data. In this model, regions of film in which the disulfide bond density is low are etched at a higher rate than regions where the density is high.

This paper presents application of laser micro-machining (LMM) in introducing a longitudinal (axial) semi-elliptical sharp notch as a pre-crack on external surface of Ti–3Al–2.5V tubes to study fatigue crack growth characteristics. The notch root radius was less than 0.03 mm. Internal impulse pressure test results were obtained for the tubes with a LMM notch of 0.23 mm deep and 0.25 aspect ratio under different internal pressure levels. Fatigue crack growth life was predicted for the tubes and validated by the experimental life data. It is observed that all predicted crack growth life data based on both NASGRO equation and Paris’ law are in good agreement with the experimental life data. Modeling and experimental results indicate that LMM is an appropriate tool for introducing a pre-crack to study fatigue crack growth in titanium and possibly other materials.