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We present a straightforward approach with high moldability for producing dual-responsive and multi-functional plasmonic hydrogel valves and biomimetic architectures that reversibly change volumes and colors in response to temperature and ion variations. Heating of a mixture of hybrid colloids (gold nanoparticles assembled on a hydrogel colloid) and hydrogel colloids rapidly induces (within 30 min) the formation of hydrogel architectures resembling mold shapes (cylinder, fish, butterfly). The biomimetic fish and butterfly display reversible changes in volumes and colors with variations of temperature and ionic conditions in aqueous solutions. The cylindrical plasmonic valves installed in flow tubes rapidly control water flow rate in on-off manner by responding to these stimuli. They also report these changes in terms of their colors. Therefore, the approach presented here might be helpful in developing new class of biomimetic and flow control systems where liquid conditions should be visually notified (e.g., glucose or ion concentration changes).

We present a plasmonic-based strategy for the colourimetric and spectroscopic differentiation of various organic acids produced by bacteria. The strategy is based on our discovery that particular concentrations of dl-lactic, acetic, and butyric acids induce different assembly structures, colours, and optical spectra of gold nanoparticles. We selected wild-type (K-12 W3110) and genetically-engineered (JHL61) Escherichia coli (E. coli) that are known to primarily produce acetic and butyric acid, respectively. Different assembly structures and optical properties of gold nanoparticles were observed when different organic acids, obtained after the removal of acid-producing bacteria, were mixed with gold nanoparticles. Moreover, at moderate cell concentrations of K-12 W3110 E. coli, which produce sufficient amounts of acetic acid to induce the assembly of gold nanoparticles, a direct estimate of the number of bacteria was possible based on time-course colour change observations of gold nanoparticle aqueous suspensions. The plasmonic-based colourimetric and spectroscopic methods described here may enable onsite testing for the identification of organic acids produced by bacteria and the estimation of bacterial numbers, which have applications in health and environmental sciences., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We present a route that estimates the scattering/absorption characteristics of plasmonic nanoparticles by using fluorescence and UV-visible spectroscopy. Because elastic scattering of nanoparticles caused by a monochromatic incident light is reflected in fluorescence emission spectra when recording at the excitation wavelength, the scattering intensities at the excitation wavelength during fluorescence emission scans are used to compare the scattering characteristics of various plasmonic nanoparticles under conditions where the extinction values of all of the nanoparticles are kept constant at this wavelength. For the two excitation wavelengths (519 and 560 nm) we investigated, the scattering intensities of spherical gold nanoparticles increase with increasing size (15, 33, 51, 73, and 103 nm in diameter). These results are correlated with the nanoparticles' scattering efficiencies (the ratios of scattering to the extinction cross-sections), which are theoretically calculated in the literature using Mie theory. Then, linear calibration equations at each wavelength are derived to estimate the scattering efficiencies of two Au nanorods, Au nanocages, and spherical Ag nanoparticles (15, 25, 37, and 62 nm). The values are very comparable with literature values. For various purposes such as biomedicine and optoelectronics, the present method could be beneficial to those who wish to easily compare and determine the scattering characteristics of various plasmonic nanoparticles at a certain wavelength by using commercially-available spectroscopic techniques.

p53R2 is a p53-inducible human ribonucleotide reductase subunit involved in critical cellular mechanisms, such as DNA repair, cell cycle arrest, and mitochondrial homeostasis. Molecular investigations and animal studies have revealed functional regulations of p53R2 and its disease relevance. The relationship between p53R2 expression and disease progression in different cancers has been evaluated, and researchers have discovered novel transcription factors and cellular mechanisms that control p53R2 in a p53-independent manner. In addition, p53R2-Mediated mechanisms that affect mitochondria, inflammation, and cancer have been addressed. The role of p53R2 in mitochondria diseases and in cancer is discussed. Finally, p53R2 is taken as a potential target for cancer treatment. This review summarizes the general background, novel regulatory findings, and medical prospect of p53R2., (Copyright © 2016. Published by Elsevier B.V.)

[Purpose] The purpose of the study was to closely examine the efficiency of Swiss ball exercise and resistance exercise in improving the on the static balancing ability by applying them to patients with scoliosis and to compare the effects of the interventions. [Subjects] Forty scoliosis patients were divided into a Swiss ball exercise group (SEG, N = 20) and a Resistance exercise group (REG, N = 20) randomly. [Methods] SEG conducted chest stretching, trunk exercise using the Swiss ball. REG conducted chest stretching, trunk exercise with therapist's resistance. Both groups received training 30 min per day, five times per week, for eight weeks. [Results] Both SEG and REG showed significant differences between pre- and post-mediation in terms of weight distribution, sway area, sway length, sway speed, and limit of stability. Sway speed and limit of stability had increased more significantly in REG than in SEG. [Conclusion] According to the result of this study, both Swiss ball exercise and chest Resistance exercise were effective for improving on the static balancing ability. But we suggest resistance exercise is more efficient to increase of sway speed, limit of stability.

We present a simple and industrially accessible method of producing liquid crystalline lipid nanoparticles with various internal structures based on phytantriol, Pluronic F127, and vitamin E acetate. Bilayer vesicles were produced when an ethanolic solution dissolving the lipid components was mixed with deionized water. After the evaporation of ethanol from the aqueous mixture, vesicles were transformed into lipid-filled liquid crystalline nanoparticles with well-defined internal structures such as hexagonal lattices (mostly inverted cubic Pn3m), lined or coiled pattern (inverted hexagonal H2), and disordered structure (inverse microemulsion, L2), depending on the compositions. Further studies suggested that their internal structures were also affected by temperature. The internal structures were characterized from cryo-TEM and small-angle X-ray scattering results. Microcalorimetry studies were performed to investigate the degree of molecular ordering/crystallinity of lipid components within the nanostructures. From the comparative studies, we demonstrated the present method could produce the lipid nanoparticles with similar characteristics to those made from a conventional method. More importantly, the production only requires simple tools for mixing and ethanol evaporation and it is possible to produce 10 kg or so per batch of aqueous lipid nanoparticles dispersions, enabling the large-scale production of the liquid crystalline nanoparticles for various biomedical applications.

[Purpose] The purpose of this study was to determine the effects of training using dual tasks on balance ability in stroke patients. [Subjects] Forty stroke patients were divided into a dual-task training group (N = 20) and a single task training group (N = 20) randomly. [Methods] The subjects in the single-task traing group stood in a comfortable position, faced a therapist, then threw a Swiss ball back and forth. They then performed balance training in which they raised and lowered their ankles while facing forward or moved objects from one table to another. The DTG performed dual tasks, which involved performing a task on an unstable surface using a balance pad. Both groups received training 30 min per day, five times per week, for eight weeks. [Results] The DTG showed significant increases in weight distribution rate, anterior limit of stability, posterior limit of stability, and BBS scores compared with the STG. [Conclusion] According to the results of this study, dual-task training and single-task training were effective in improving balance in stroke patients, dual task training is more effective for increasing balance ability.

We developed a route for synthesizing Ag nanostructures with tunable morphologies for ultrasensitive surface-enhanced Raman spectroscopy. Through the consecutive addition of three reducing agents (i.e., 4-mercaptobenzoic acid, trisodium citrate, and ascorbic acid) to an aqueous solution of silver nitrate, hierarchical flower-like Ag nanostructures were produced. The nanostructures had Ag petals in which nanosized gaps were generated, and small Ag nanoparticles were incorporated within the gaps. Theoretically, the nanostructures exhibited highly enhanced electric fields in the outer-shell regions where the small Ag nanoparticles were densely located. Combining the enhanced field effect with resonance effect of a Raman-active molecule (methylene blue) at a specific wavelength, measurable Raman signals were obtained at concentrations as low as 100 attomolar (10(-16) M; corresponding to 10(-21) mol). Key factors were discussed for the synthesis of the Ag nanostructures while finely controlling the morphologies of hierarchical Ag nanostructures, thereby modulating the intensity of surface-enhanced resonance Raman spectroscopy (SERRS) signals. Therefore, this synthetic method produces highly promising nanostructures for SERRS-based applications.

[Purpose] The purpose of the study was to determine the effects of training using virtual reality games on balance and gait ability, as well as the psychological characteristics of stroke patients, such as depression and interpersonal relationships, by comparing them with the effects of ergometer training. [Subjects] Forty stroke patients were randomly divided into a virtual reality group (VRG, N = 20) and an ergometer training group (ETG, N = 20). [Methods] VRG performed training using the Xbox Kinect. ETG performed training using an ergometer bicycle. Both groups received training 30 min per day, five times per week, for eight weeks. [Results] Both the VRG and ETG subjects exhibited a significant difference in weight distribution ratio on the paralyzed side and balance ability. Both the VRG and ETG patients showed significant improvement in psychological measures BDI and RCS, after the intervention, and the VRG sowed a more significant increase in BDI than the ETG. [Conclusion] According to the result of this study, virtual reality training and ergometer training were both effective at improving balance, gait abilities, depression, and interpersonal relationships among stroke patients.

We have synthesized conductive nanocomposites composed of multiwalled carbon nanotubes (MWCNTs) and Au nanoparticles (NPs). The Au NPs with an average size of approximately 4.3 nm are uniformly anchored on the MWCNT. After being exposed to microwave (MW) plasma irradiation, the anchored Au NPs melt and fuse, leading to larger aggregates (34 nm) that can connect the MWCNT forming a three-dimensional conducting network. The formation of a continuous MWCNT network can produce more a conductive pathway, leading to lower sheet resistance. When the Au-MWCNT is dispersed in the highly conductive polymer, poly(ethylene dioxythiophene):polystyrenesulfonate (, Pedot: PSS), we can obtain solution-processable composite formulations for the preparation of a flexible transparent electrode. The resulting Au-MWCNT/PEDOT:PSS hybrid films possess a sheet resistance of 51 Ω/sq with a transmittance of 86.2% at 550 nm. We also fabricate flexible organic solar cells and electrochromic devices to demonstrate the potential use of the as-prepared composite electrodes. Compared with the indium tin oxide-based devices, both the solar cells and electrochromic devices with the composites incorporated as a transparent electrode deliver comparable performance.

[Purpose] The purpose of this study was to examine the efficiency of chest resistance and chest expansion exercises for improving respiratory function and trunk control ability in patients with stroke. [Subjects] Forty patients with stroke were randomly allocated into a chest resistance exercise group (CREG, n = 20) and a chest expansion exercise group (CEEG, n = 20). [Methods] CREG patients underwent chest resistance exercises, and diaphragmatic resistance exercises by way of the proprioceptive neuromuscular facilitation. CEEG patients underwent respiratory exercises with chest expansion in various positions. Both groups received 30 minutes of training per day, five times per week, for eight weeks. [Results] Both the CERG and CEEG groups showed significant changes in FVC, FEV1, and TIS after the intervention. TIS was significantly increased in the CREG compared to the CEEG after the intervention. [Conclusion] Both chest resistance and chest expansion exercises were effective for improving respiratory function and trunk control ability in stroke patients; however, chest resistance exercise is more efficient for increasing trunk control ability.

[Purpose] This study compared the effects of Swiss ball exercise and resistance exercise on the respiratory function and trunk control ability of patients with scoliosis. [Subjects] Forty scoliosis patients were randomly divided into the Swiss ball exercise group (n= 20) and resistance exercise group (n = 20). [Methods] The Swiss ball and resistance exercise groups performed chest expansion and breathing exercises with a Swiss ball and a therapist's resistance, respectively. Both groups received training 30 min per day, 5 times per week for 8 weeks. [Results] Both groups exhibited significant changes in forced vital capacity, forced expiratory volume in one second, and trunk impairment scale after the intervention. However, there was no significant change in the forced expiratory volume in one second/forced vital capacity ratio after the intervention in either group. Meanwhile, forced expiratory volume in one second and trunk impairment scale were significantly greater in the resistance exercise group after the intervention. [Conclusion] Both Swiss ball exercise and resistance exercise are effective for improving the respiratory function and trunk control ability of patients with scoliosis. However, resistance exercise is more effective for increasing the forced expiratory volume in one second and trunk control ability.

[Purpose] The aim of this study was to examine the effects of ball exercise as a general exercise on the balance abilities of elderly individuals by comparing ball exercise with virtual reality exercise. [Subjects and Methods] Thirty elderly individuals residing in communities were randomly divided into a virtual reality game group and a ball exercise group and conducted exercise for 30 min 3 times a week for 8 weeks. [Results] Step length increased significantly, and the average sway speed and Timed Up and Go time significantly decreased in both groups. A comparison of sway length after the intervention between the two groups revealed that the virtual reality game exercise resulted in a reduction than the ball exercise. [Conclusion] The results of this study indicated that the virtual reality game exercise may improve balance and gait of elderly individuals in communities.

[Purpose] The purpose of the study was to investigate the effects of action observation training on the static balance and walking ability of patients who had suffered a stroke. [Subjects] Forty patients with hemiplegia resulting from a stroke were divided into an action observation gait training group (AOGT group, n=20) and a general gait training group (GGT group, n=20). [Methods] The AOGT group watched a training video on flatland gait, slope gait, and stair gait. The GGT group watched a video on nature. Both groups watched their respective video for 10 minutes and then had gait training for 20 minutes per day, five times per week, for eight weeks. [Results] The static balance and gait ability of both groups significantly improved. Although there were significant differences between the groups, the AOTG group showed greater improvements in sway speed, limit of stability, and gait ability. [Conclusion] We recommend action observation training over general gait training for patients with hemiplegia. Action observational training had a positive effect on static balance and gait ability in stroke patients' static balance and gait ability. Further research is needed to generalize the results of this study.

RRM2B is a critical ribonucleotide reductase (RR) subunit that exists as p53-inducible and p53-dependent molecule. The p53-independent regulation of RRM2B has been recently studied, and FOXO3 was identified as a novel regulator of RRM2B. However, the p53-independent regulation of RRM2B, particularly under oxidative stress, remains largely unknown. In this study, we investigated the role of RRM2B underoxidative stress-induced DNA damage and further examined the regulation of mitochondrial and inflammatory genes by RRM2B. Our study is the first to report the critical role of RRM2B in mitochondrial homeostasis and the inflammation signaling pathway in a p53-independent manner. Furthermore, our study provides novel insights into the role of the RR in inflammatory diseases.

Graves' disease, the main cause of hyperthyroidism in the pediatric age group, is very rare in children younger than 4 years old but can seriously interfere with growth and development if not recognized and treated. Here we report a case of a 3-year-old girl with Graves' disease who presented with goiter, exophthalmos, heat intolerance, and hyperactivity. At her first visit, her serum concentrations of triiodothyronine (T3) and free thyroxine (free T4) were normal, whereas that of thyroid-stimulating hormone (TSH) was decreased. Antimicrosomal antibody was 7,053.94 IU/mL, and TSH-binding inhibitory immunoglobulin was 31.62%. A thyroid scan showed diffuse enlargement with markedly increased uptake of both thyroid glands. Although T3 and free T4 levels were initially normal, she developed hyperthyroidism 3 months later. She was finally diagnosed with Graves' disease and treated with methimazole for 6 months. This is the first report of Graves' disease in children younger than 4 years old in Korea.

The role of Ribonucleotide reductase (RR) subunits in different cancers has been intensively studied in our laboratory. RRM2B was identified as a p53-inducible RR subunit that involves in various critical cellular mechanisms such as cell cycle regulation, DNA repair and replication, and mitochondrial homeostasis, etc. However, little is known about the p53-independent regulation of RRM2B in cancer pathology. In this study, we discovered tumor suppressor FOXO3 as the novel regulator of RRM2B. FOXO3 directly bound to and transcriptionally activated the promoter of RRM2B, and induced the expression of RRM2B at RNA and protein levels. Moreover, Overexpression of RRM2B and/or FOXO3 inhibited the proliferation of cancer cells. The cancer tissue microarray data also demonstrated a strong correlation between the co-expression of FOXO3 plus RRM2B and increased disease survival and reduced recurrence or metastasis in lung cancer patients. Our results suggest a novel regulatory control of RRM2B function, and imply the importance of FOXO signaling pathway in DNA replication modulation. This study provides the first time evidence that RRM2B is transcriptionally and functionally regulated independent of p53 pathway by FOXO3, and it establishes that FOXO3 and RRM2B could be used as predictive biomarkers for cancer progression.

We report a method for controlling the detection sensitivity to or the degree of etching of Ag nanocubes by radicals by modifying their surfaces with poly(acrylic acid) or poly(allylamine hydrochloride) for wide-range quantification of radical compounds. The degree of Ag nanocube etching is influenced by the concentrations of the polyelectrolytes used for modification. These polyelectrolytes protect the Ag nanocubes, probably by either retarding (forming diffusion barriers) or preventing (blocking/entrapping/scavenging) the arrival of radicals to Ag nanocubes, or both. The weights of the two roles are different depending on the polyelectrolyte type; therefore, the sensitivities of Ag nanocubes are also influenced by this factor. The roles of the polyelectrolytes were demonstrated by using radical compounds produced from tetrahydrofuran and H2O2 and further confirmed with Ag nanospheres. Using the results, the radical sensitivities and detection ranges of polyelectrolyte-modified Ag nanoparticles could be manipulated. Moreover, we produced calibration curves for the wide-range quantification of radical compounds.

The Human Rhinovirus (HRV) is the major aetiological agent for the common cold, for which only symptomatic treatment is available. HRV maturation and replication is entirely dependent on the activity of a virally encoded 3C protease that represents an attractive target for the development of therapeutics to treat the common cold. Herein we report the synthesis and biological evaluation of the 2-methylene analogue of the HRV 3C protease inhibitor (-)-thysanone (1) namely 2-carbathysanone (2), in an attempt to decipher the structural features in the natural product that are responsible for the 3C protease activity. 2-Carbathysanone (2) (and related analogues (±)-cis-23, (±)-cis-30, (±)-31) did not inhibit HRV 3C protease, indicating that the lactol functionality present in (-)-thysanone (1) is a critical structural feature required for inhibition.

MicroRNA-34b down-regulation in acute myeloid leukemia was previously shown to induce CREB overexpression, thereby causing leukemia proliferation in vitro and in vivo. The role of microRNA-34b and CREB in patients with myeloid malignancies has never been evaluated. We examined microRNA-34b expression and the methylation status of its promoter in cells from patients diagnosed with myeloid malignancies. We used gene expression profiling to identify signatures of myeloid transformation. We established that microRNA-34b has suppressor ability and that CREB has oncogenic potential in primary bone marrow cell cultures and in vivo. MicroRNA-34b was found to be up-regulated in pediatric patients with juvenile myelomonocytic leukemia (n=17) and myelodysplastic syndromes (n=28), but was down-regulated in acute myeloid leukemia patients at diagnosis (n=112). Our results showed that hypermethylation of the microRNA-34b promoter occurred in 66% of cases of acute myeloid leukemia explaining the low microRNA-34b levels and CREB overexpression, whereas preleukemic myelodysplastic syndromes and juvenile myelomonocytic leukemia were not associated with hypermethylation or CREB overexpression. In paired samples taken from the same patients when they had myelodysplastic syndrome and again during the subsequent acute myeloid leukemia, we confirmed microRNA-34b promoter hypermethylation at leukemia onset, with 103 CREB target genes differentially expressed between the two disease stages. This subset of CREB targets was confirmed to associate with high-risk myelodysplastic syndromes in a separate cohort of patients (n=20). Seventy-eight of these 103 CREB targets were also differentially expressed between healthy samples (n=11) and de novo acute myeloid leukemia (n=72). Further, low microRNA-34b and high CREB expression levels induced aberrant myelopoiesis through CREB-dependent pathways in vitro and in vivo. In conclusion, we suggest that microRNA-34b controls CREB expression and contributes to myeloid transformation from both healthy bone marrow and myelodysplastic syndromes. We identified a subset of CREB target genes that represents a novel transcriptional network that may control myeloid transformation.

The cAMP response element-binding protein (CREB) is a nuclear transcription factor that is critical for normal and neoplastic hematopoiesis. Previous studies have demonstrated that CREB is a proto-oncogene whose overexpression promotes cellular proliferation in hematopoietic cells. Transgenic mice that overexpress CREB in myeloid cells develop a myeloproliferative disease with splenomegaly and aberrant myelopoiesis. However, CREB overexpressing mice do not spontaneously develop acute myeloid leukemia. In this study, we used retroviral insertional mutagenesis to identify genes that accelerate leukemia in CREB transgenic mice. Our mutagenesis screen identified several integration sites, including oncogenes Gfi1, Myb, and Ras. The Sox4 transcription factor was identified by our screen as a gene that cooperates with CREB in myeloid leukemogenesis. We show that the transduction of CREB transgenic mouse bone marrow cells with a Sox4 retrovirus increases survival and self-renewal of cells in vitro. Furthermore, leukemic blasts from the majority of acute myeloid leukemia patients have higher CREB, phosphorylated CREB, and Sox 4 protein expression. Sox4 transduction of mouse bone marrow cells results in increased expression of CREB target genes. We also demonstrate that CREB is a direct target of Sox4 by chromatin immunoprecipitation assays. These results indicate that Sox4 and CREB cooperate and contribute to increased proliferation of hematopoietic progenitor cells.

The recovery of skin barrier functions was investigated with pseudo-ceramide-based lipid microparticles. The microparticles were prepared by using a fluid bed technique where lipid components (a pseudo-ceramide, cholesterol and a fatty acid) were coated on a sugar seed, and a polymer was subsequently coated on the lipid microparticles. The microparticles contained large amount of pseudo-ceramide, and the pseudo-ceramide was in the form of lamellar structures mixed with other lipid components. In addition, the microparticles were stably dispersed in aqueous media or emulsion systems without any disruption of the microparticles' structures, thereby supplying sufficient amount of the pseudo-ceramide to skins for improving skin barrier functions such as preventing water loss. Such a role of the microparticles was proven by evaluating in vivo the efficacy of the lipid microparticles in reducing a trans-epidermal water loss (TEWL) of impaired murine skins. As a result, the novel pseudo-ceramide-based lipid microparticles for barrier recovery may potentially be applied in the field of dermatology, cosmetics and pharmaceuticals., (Copyright © 2012 Elsevier B.V. All rights reserved.)

E2F transcription factors are implicated in diverse cellular functions. The founding member, E2F-1, is endowed with contradictory activities, being able to promote cell-cycle progression and induce apoptosis. However, the mechanisms that underlie the opposing outcomes of E2F-1 activation remain largely unknown. We show here that E2F-1 is directly methylated by PRMT5 (protein arginine methyltransferase 5), and that arginine methylation is responsible for regulating its biochemical and functional properties, which impacts on E2F-1-dependent growth control. Thus, depleting PRMT5 causes increased E2F-1 protein levels, which coincides with decreased growth rate and associated apoptosis. Arginine methylation influences E2F-1 protein stability, and the enhanced transcription of a variety of downstream target genes reflects increased E2F-1 DNA-binding activity. Importantly, E2F-1 is methylated in tumour cells, and a reduced level of methylation is evident under DNA damage conditions that allow E2F-1 stabilization and give rise to apoptosis. Significantly, in a subgroup of colorectal cancer, high levels of PRMT5 frequently coincide with low levels of E2F-1 and reflect a poor clinical outcome. Our results establish that arginine methylation regulates the biological activity of E2F-1 activity, and raise the possibility that arginine methylation contributes to tumourigenesis by influencing the E2F pathway.

We present a rapid and sensitive surface acoustic wave (SAW) immunosensor that utilizes gold staining as a signal enhancement method. A sandwich immunoassay was performed on sensing area of the SAW sensor, which could specifically capture and detect cardiac markers (cardiac troponin I (cTnI), creatine kinase (CK)-MB, and myoglobin). The analytes in human serum were captured on gold nanoparticles (AuNPs) that were conjugated in advance with detection antibodies. Introduction of these complexes to the capture antibody-immobilized sensor surface resulted in a classic AuNP-based sandwich immunoassay format that has been used for signal amplification. In order to achieve further signal enhancement, a gold staining method was performed, which demonstrated that it is possible to obtain gold staining-mediated signal augmentation on a mass-sensitive device. The sensor response due to gold staining varied as a function of cardiac marker concentration. We also investigated effects of increasing operating frequency on sensor responses. Results showed that detection limit of the SAW sensor could be further improved by increasing the operating frequency.

Central to discovering novel approaches to treating leukemias and lymphomas is a clear understanding of the signaling networks which lead to unchecked cell cycle progression, proliferation, and survival. Cyclic-adenosine monophosphate (cAMP) responsive element-binding protein (CREB) represents a critical integrator of numerous signals from cytoplasmic kinase cascades, and is directly involved in controlling the transcription of genes critical for normal cellular proliferation and survival. Several lines of evidence implicate CREB as a proto-oncogene, as a number of translocations involving CREB and dysregulation of expression are both associated with oncogenesis. Thus, CREB represents a potential therapeutic target in leukemia. Here, we review CREB function and regulation in normal and aberrant hematopoiesis.

Gold nanostructures have garnered considerable attention in recent years for their potential to facilitate both the diagnosis and treatment of cancer through their advantageous chemical and physical properties. The key feature of Au nanostructures for enabling this diverse array of biomedical applications is their attractive optical properties, specifically the scattering and absorption of light at resonant wavelengths due to the excitation of plasmon oscillations. This phenomenon is commonly known as localized surface plasmon resonance (LSPR) and is the source of the ruby red color of conventional Au colloids. The resonant wavelength depends on the size, shape, and geometry of the nanostructures, providing a set of knobs to manipulate the optical properties as needed. For in vivo applications, especially when optical excitation or transduction is involved, the LSPR peaks of the Au nanostructures have to be tuned to the transparent window of soft tissues in the near-infrared (NIR) region (from 700 to 900 nm) to maximize the penetration depth. Gold nanocages represent one class of nanostructures with tunable LSPR peaks in the NIR region. These versatile nanostructures, characterized by hollow interiors and ultrathin, porous walls, can be prepared in relatively large quantities using a remarkably simple procedure based on the galvanic replacement between Ag nanocubes and aqueous chloroauric acid. The LSPR peaks of Au nanocages can be readily and precisely tuned to any wavelength in the NIR region by controlling their size, wall thickness, or both. Other significant features of Au nanocages that make them particularly intriguing materials for biomedical applications include their compact sizes, large absorption cross sections (almost five orders of magnitude greater than those of conventional organic dyes), and their bio-inertness, as well as a robust and straightforward procedure for surface modification based on Au-thiolate chemistry. In this Account, we present some of the most recent advances in the use of Au nanocages for a broad range of theranostic applications. First, we describe their use as tracers for tracking by multiphoton luminescence. Gold nanocages can also serve as contrast agents for photoacoustic (PA) and mutimodal (PA/fluorescence) imaging. In addition, these nanostructures can be used as photothermal agents for the selective destruction of cancerous or diseased tissue. Finally, Au nanocages can serve as drug delivery vehicles for controlled and localized release in response to external stimuli such as NIR radiation or high-intensity focused ultrasound (HIFU).

In vitro experiments typically measure the uptake of nanoparticles by exposing cells at the bottom of a culture plate to a suspension of nanoparticles, and it is generally assumed that this suspension is well-dispersed. However, nanoparticles can sediment, which means that the concentration of nanoparticles on the cell surface may be higher than the initial bulk concentration, and this could lead to increased uptake by cells. Here, we use upright and inverted cell culture configurations to show that cellular uptake of gold nanoparticles depends on the sedimentation and diffusion velocities of the nanoparticles and is independent of size, shape, density, surface coating and initial concentration of the nanoparticles. Generally, more nanoparticles are taken up in the upright configuration than in the inverted one, and nanoparticles with faster sedimentation rates showed greater differences in uptake between the two configurations. Our results suggest that sedimentation needs to be considered when performing in vitro studies for large and/or heavy nanoparticles.

This communication reports a new theranostic system with a combination of capabilities to both enhance the contrast of photoacoustic (PA) imaging and control the release of a chemical or biological effector by high-intensity focused ultrasound (HIFU). The fabrication of this system simply involves filling the hollow interiors of gold nanocages with a phase-change material (PCM) such as 1-tetradecanol that has a melting point of 38-39 °C. The PCM can be premixed and thus loaded with a dye, as well as other chemical or biological effectors. When exposed to direct heating or HIFU, the PCM will melt and escape from the interiors of nanocages through small pores on the surface, concurrently releasing the encapsulated molecules into the surrounding medium. We can control the release profile by varying the power of HIFU, the duration of exposure to HIFU, or both., (© 2011 American Chemical Society)

Acute myeloid leukemia (AML) is one of the most common leukemias with a 20% 5-year event-free survival in adults and 50% overall survival in children, despite aggressive chemotherapy treatment and bone marrow transplantation. The incidence and mortality rates for acute leukemia have only slightly decreased over the last 20 years, and therefore greater understanding of the molecular mechanisms associated with leukemic progression is needed. To this end, a number of transcription factors that appear to play a central role in leukemogenesis are being investigated; among them is the cAMP response element binding protein (CREB). CREB is a transcription factor that can regulate downstream targets involving in various cellular functions including cell proliferation, survival, and differentiation. In several studies, the majority of bone marrow samples from patients with acute lymphoid and myeloid leukemia demonstrate CREB overexpression. Moreover, CREB overexpression is associated with a poor outcome in AML patients. This review summarizes the role of CREB in leukemogenesis.

Gold nanostructures have proven to be a versatile platform for a broad range of biomedical applications, with potential use in numerous areas including: diagnostics and sensing, in vitro and in vivo imaging, and therapeutic techniques. These applications are possible because of the highly favorable properties of gold nanostructures, many of which can be tailored for specific applications. In the first part of this tutorial review, we will discuss the most critical properties of gold nanostructures for biomedical applications: surface chemistry, localized surface plasmon resonance (LSPR), and morphology. In the second part of the review, we will discuss how these properties can be harnessed for a selection of biomedical applications, aiming to give the reader an overview of general strategies as well as highlight some recent advances in this field.

Inorganic nanoparticles (NPs) including semiconductor quantum dots (QDs), iron oxide NPs and gold NPs have been developed as contrast agents for diagnostics by molecular imaging. Compared with traditional contrast agents, NPs offer several advantages: their optical and magnetic properties can be tailored by engineering the composition, structure, size and shape; their surfaces can be modified with ligands to target specific biomarkers of disease; the contrast enhancement provided can be equivalent to millions of molecular counterparts; and they can be integrated with a combination of different functions for multimodal imaging. Here, we review recent advances in the development of contrast agents based on inorganic NPs for molecular imaging, and also touch on contrast enhancement, surface modification, tissue targeting, clearance and toxicity. As research efforts intensify, contrast agents based on inorganic NPs that are highly sensitive, target-specific and safe to use are expected to enter clinical applications in the near future., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

This paper describes a facile method for generating Au@Ag core-shell nanocubes with edge lengths controllable in the range of 13.4-50 nm. The synthesis involved the use of single-crystal, spherical Au nanocrystals of 11 nm in size as the seeds in an aqueous system, with ascorbic acid serving as the reductant and cetyltrimethylammonium chloride (CTAC) as the capping agent. The thickness of the Ag shells could be finely tuned from 1.2 to 20 nm by varying the ratio of AgNO(3) precursor to Au seeds. We also investigated the growth mechanism by examining the effects of seeds (capped by CTAC or cetyltrimethylammonium bromide(CTAB)) and capping agent (CTAC vs CTAB) on both size and shape of the resultant core-shell nanocrystals. Our results clearly indicate that CTAC worked much better than CTAB as a capping agent in both the syntheses of Au seeds and Au@Ag core-shell nanocubes. We further studied the localized surface plasmon resonance properties of the Au@Ag nanocubes as a function of the Ag shell thickness. By comparing with the extinction spectra obtained from theoretical calculations, we derived a critical value of ca. 3 nm for the shell thickness at which the plasmon excitation of the Au cores would be completely screened by the Ag shells. Moreover, these Au@Ag core-shell nanocubes could be converted into Au-based hollow nanostructures containing the original Au seeds in the interiors through a galvanic replacement reaction.

Gold nanocages represent a novel class of nanostructures, well-suited for biomedical applications. They can be readily prepared via the galvanic replacement reaction between silver nanocubes and chloroauric acid. Their optical resonance peaks can be easily and precisely tuned to the near-infrared region from 650-900 nm, the transparent window for blood and soft tissue. Furthermore, their surface can be conveniently conjugated with various ligands for targeting cancer. In this feature article, we highlight recent advances in the large-scale synthesis of gold nanocages and their applications in cancer diagnosis and treatment. Specifically, we have scaled up the production of gold nanocages for in vivo studies and evaluated their tumor targeting capabilities. We have also demonstrated their use as contrast agents for photoacoustic tumor imaging and the mapping of sentinel lymph node, as photothermal transducers for cancer treatment, and as smart carriers for controlled release with a near-infrared laser.

Early diagnosis, accurate staging, and image-guided resection of melanomas remain crucial clinical objectives for improving patient survival and treatment outcomes. Conventional techniques cannot meet this demand because of the low sensitivity, low specificity, poor spatial resolution, shallow penetration, and/or ionizing radiation. Here we overcome such limitations by combining high-resolution photoacoustic tomography (PAT) with extraordinarily optical absorbing gold nanocages (AuNCs). When bioconjugated with [Nle(4),D-Phe(7)]-alpha-melanocyte-stimulating hormone, the AuNCs can serve as a novel contrast agent for in vivo molecular PAT of melanomas with both exquisite sensitivity and high specificity. The bioconjugated AuNCs enhanced contrast approximately 300% more than the control, PEGylated AuNCs. The in vivo PAT quantification of the amount of AuNCs accumulated in melanomas was further validated with inductively coupled plasma mass spectrometry (ICP-MS).

This article describes a simple method for controlling the assembly of gold nanoparticles (Au NPs) into chainlike structures with tunable lengths and interparticle separations. The chainlike assemblies were induced to form by adding HS(CH(2))(n)COOH (n = 2, 10, and 15) into a suspension of Au NPs in a mixture of ethanol and water (98:2 by volume). The number of Au NPs in the chainlike assemblies could be altered by varying the concentration of the thiol while the interparticle distance between Au NPs in the chain could be adjusted by using thiols of different chain lengths. The chainlike assemblies of Au NPs were structurally unstable during storage and purification. We solved this problem by fixing the chainlike assemblies with silica coating via the Stober method or by encapsulating them inside gelatin microspheres with the use of a fluidic device. After fixing, the chainlike assemblies of Au NPs could be preserved for a long period of time, during which their characteristic optical properties remained unchanged.

We present a simple method to control the volume change of thermally responsive hydrogel scaffolds, providing a remarkably fast swelling and deswelling response to temperature changes. These scaffolds have 3-dimensional colloidal-network structures which are made from microgel particles while they are above their deswelling transition temperatures. By tuning the cross-link density of the microgel particles, we achieve controllable changes of the volume of the scaffolds in response to temperature. Their fast response rate is determined by the length scale of the unit microgel particles and is not influenced by the properties of the network. The release profile of a model drug (Rhapontin) loaded within the scaffolds can also be regulated by the cross-linking density of the microgel particles. These results offer a new way of fabricating hydrogel scaffolds with tunable matrix geometry and function by adjusting the properties of the unit microgel colloids, without loss of their fast response to temperature change.

We present a novel electrochemical cell lysis device to prepare DNA samples for lab-on-a-chip (LOC) applications. It utilizes the electrolysis of saline solution to generate hydroxide ions (OH(-)) at the cathode as alkaline lytic agents. Cathode and anode chambers are separated by a negatively-charged ion exchangeable polymer diaphragm to maintain the high pH level for efficient cell lysis in the cathode chamber, to prevent inflow of PCR-amplification inhibitors from the anode chamber, and to minimize binding of DNA molecules. Electric current flow and pH maintenance, which depended on the device design, were two important parameters of the device performance. After optimizing the design and visually confirming cell lysis of Chinese hamster ovary (CHO) cells in a very short amount of time, we directly electrolyzed four bacterial cell types suspended in saline solution. Real-time PCR (qPCR) analysis showed that our device could lyse both gram-positive and gram-negative bacterial cells with higher efficiency than other common methods and could detect DNA on the microlitre scale. Our data demonstrate several advantages of the proposed device: absence of cell lysis chemicals and heating; no adverse effects on PCR amplification; low DNA loss; low voltage and power consumption; and rapid processing. The device could potentially be applied as an on-chip DNA extraction component.

We have synthesized metal-polymer hybrid colloidal particles characterized by an eccentric structure by precipitation polymerization in the presence of metal colloids. The key to the formation of an eccentric core-shell structure was to introduce metal colloids a few minutes after (rather than before) starting the polymerization. The hybrid particles were uniform in size, and each one of them contained only one metal nanoparticle at its surface after the experimental procedures had been optimized. This method could be extended to a number of different metal colloids stabilized by small molecules, and the yield was found to be more or less independent of the size of the metal nanoparticles. In addition, the position of the metal nanoparticle in the hybrid particle could be controlled by changing the concentration of cross-linker, and the overall size of the hybrid particles could be altered by solvent treatment. Because of the simplicity of this procedure, it should be possible to use it for the large-scale production of colloidal particles having a hybrid, complex structure.

We present a facile and straightforward method to fabricate liposomal membranes with a significantly stable lamellar structure consisting of pseudo-ceramide, fatty acid, and cholesterol. Characterizing their membrane properties, in which we have used differential scanning calorimetry, X-ray diffraction, and FT-IR spectra, enables us to demonstrate that pseudo-ceramide with appropriate amounts of stearic acid and cholesterol can assemble to form a stable lamellar alpha-phase. Moreover, we show that cholesterol is indeed important and plays a role in controlling the melting entropy of lipid membranes, which is attributed to a disordered molecular packing, thus creating more flexible liposomal membranes. This approach to use pseudo-ceramide offers a useful means to fabricate a variety of biocompatible liposomes with controllable membrane properties, which enlarges their applicability in the field of drug delivery, dermatology, and cosmetics.

Transient grating spectroscopy detects directly the relaxation of the excited carriers rather than time-resolved photoluminescence and thus it is particularly desired for the indirect semiconductors such as silicon quantum dots. We investigate ultrafast carrier dynamics in silicon quantum dots embedded in silicon oxide matrix using femtosecond transient grating spectroscopy. Two ultrafast decay components are observed with decay time of 800 fs and 4 ps at various detection wavelengths, which are attributed to the transverse optical and transverse acoustic phonon assisted relaxation. Photoexcited electrons and holes are effectively trapped into the localized states on the surface of the silicon quantum dots where electrons and holes have a slow recombination in the time scale of microseconds.

We demonstrate an application of Love wave mode surface acoustic wave (SAW) immunosensor to detect hepatitis B surface antibody (HBsAb) in aqueous conditions. SiO(2) guiding layer was deposited on 36 degrees YX-LiTaO(3) piezoelectric single crystal substrate to protect the electrodes and to trap the acoustic energy near the surface, and hepatitis B surface antigen (HBsAg) was immobilized on the sensing area. The resonance frequency shift was monitored to detect specific binding of HBsAb to immobilized HBsAg. To eliminate the effects of other physical factors except for the mass change, the resonance frequency was compared to that of a reference SAW device coated with bovine serum albumin (BSA) to block binding of HBsAb. The guiding layer thickness with maximum mass sensitivity was found to be 5 microm, which was in agreement with the theoretical calculation, and the center resonance frequency was around 199 MHz. The sensor showed binding specificity to HBsAb and a linear relationship between the frequency shift and the antibody concentration with sensitivity of 0.74 Hz/(pg/microl) and detection limit below 10 pg/microl. In addition, our SAW immunosensor successfully detected HBsAb in whole blood samples without any pretreatment, opening up its applicability in fast label-free protein detection methods.

Controlling the morphology of Pt nanostructures can provide a great opportunity to improve their catalytic properties and increase their activity on a mass basis. We synthesized Pd-Pt bimetallic nanodendrites consisting of a dense array of Pt branches on a Pd core by reducing K2PtCl4 with L-ascorbic acid in the presence of uniform Pd nanocrystal seeds in an aqueous solution. The Pt branches supported on faceted Pd nanocrystals exhibited relatively large surface areas and particularly active facets toward the oxygen reduction reaction (ORR), the rate-determining step in a proton-exchange membrane fuel cell. The Pd-Pt nanodendrites were two and a half times more active on the basis of equivalent Pt mass for the ORR than the state-of-the-art Pt/C catalyst and five times more active than the first-generation supportless Pt-black catalyst.

This paper presents a method for measuring the optical absorption cross-sections (σ(a)) of Au-Ag nanocages and Au nanorods. The method is based on photoacoustic (PA) imaging, where the detected signal is directly proportional to the absorption coefficient (μ(a)) of the nanostructure. For each type of nanostructure, we firstly obtained μ(a) from the PA signal by benchmarking against a linear calibration curve (PA signal vs. μ(a)) derived from a set of methylene blue solutions with different concentrations. We then calculated σ(a) by dividing the μ(a) by the corresponding concentration of the Au nanostructure. Additonally, we obtained the extinction cross-section (σ(e), sum of absorption and scattering) from the extinction spectrum recorded using a conventional UV-vis-NIR spectrometer. From the measurements of σ(a) and σ(e), we were able to easily derive both the absorption and scattering cross-sections for each type of gold nanostructure. The ratios of absorption to extinction obtained from experimental and theoretical approaches agreed well, demonstrating the potential use of this method in determining the optical absorption and scattering properties of gold nanostructures and other types of nanomaterials.