Search

This paper details Australian commercial and academic silicon research. Areas of interest include silicon metal, polysiloxane polymers, copolymers, cyclics, emulsions, microemulsions, silanes, silane coupling agents, sol-gel chemistry and water-treatments, porous silicon, polysiloxane degradation, silicon hydrogel contact lenses, silanolate synthesis, siloxane interfacial polymerisation, hydrosilylation, polysiloxane electrolytes for lithium ion batteries, silanes for PBX materials, octafunctionalized polyhedral oligomeric silsesquioxanes (POSS), POSS hybrids, sol-gel hydrogenation catalysts, silane modification of silica, sol-gel energy storage, silicate grout stabilisation, GeoPolymer concretes, aerogel insulating foams, "Phaco-Ersatz" Accommodating Gel-Intraocular Lens technologies. Strong collaborative opportunities, in silicon, with Asia, exist with organisations such as: 1) The Asian Silicon Society and 2) The Agency for the Assessment and Application of Technology (BPPT) Indonesia., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

CYP 106A2 from Bacillus megaterium ATCC 13368 has been described as a 15β-hydroxylase showing also minor 11α-, 9α- and 6β-hydroxylase activity for progesterone conversion. Previously, mutant proteins with a changed selectivity towards 11α-OH-progesterone have already been produced. The challenge of this work was to create mutant proteins with a higher regioselectivity towards hydroxylation at positions 9 and 6 of the steroid molecule. 9α-hydroxyprogesterone exhibits pharmaceutical importance, because it is a useful intermediate in the production of physiologically active substances which possess progestational activity. Sixteen mutant proteins were selected from a library containing mutated proteins created by a combination of site-directed and saturation mutagenesis of active site residues. Four mutant proteins out of these catalyzed the conversion of progesterone to 9α-OH-progesterone as a main product. For further optimization site-directed mutagenesis was performed. The introduction of seven mutations (D217V, A243V, A106T, F165L, T89N, T247V or T247W) into these four mutant proteins led to 28 new variants, which were also used for an in vivo conversion of progesterone. The best mutant protein, F165L/A395E/G397V, showed a ten-fold increase in the selectivity towards progesterone 9α-hydroxylation compared with the wild type CYP106A2. Also 6β-OH-progesterone is a pharmaceutically important compound, especially as intermediate for the production of drugs against breast cancer. For the rational design of mutant proteins with 6β-selectivity, docking of the 3D-structure of CYP106A2 with progesterone was performed. The introduction of three mutations (T247A, A243S, F173A) led to seven new mutant proteins. Clone A243S showed the greatest improvement in 6β-selectivity being more than ten-fold. Finally, an in vivo conversion of 11-deoxycorticosterone (DOC), testosterone and cortisol with the best five mutant proteins displaying 9α- or 6β-hydroxylation, respectively, of progesterone was performed to investigate whether the introduced mutations also effected the conversion of other substrates., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Ascertainment of hospitalizations is critical to assess quality of care and the effectiveness and adverse effects of various therapies. Smartphones, mobile geolocators that are ubiquitous, have not been leveraged to ascertain hospitalizations. Therefore, we evaluated the use of smartphone-based geofencing to track hospitalizations., Methods and Results: Participants aged ≥18 years installed a mobile application programmed to geofence all hospitals using global positioning systems and cell phone tower triangulation and to trigger a smartphone-based questionnaire when located in a hospital for ≥4 hours. An in-person study included consecutive consenting patients scheduled for electrophysiology and cardiac catheterization procedures. A remote arm invited Health eHeart Study participants who consented and engaged with the study via the internet only. The accuracy of application-detected hospitalizations was confirmed by medical record review as the reference standard. Of 22 eligible in-person patients, 17 hospitalizations were detected (sensitivity 77%; 95% confidence interval, 55%-92%). The length of stay according to the application was positively correlated with the length of stay ascertained via the electronic medical record ( r =0.53; P =0.03). In the remote arm, the application was downloaded by 3443 participants residing in all 50 US states; 243 hospital visits at 119 different hospitals were detected through the application. The positive predictive value for an application-reported hospitalization was 65% (95% confidence interval, 57%-72%)., Conclusions: Mobile application-based ascertainment of hospitalizations can be achieved with modest accuracy. This first proof of concept may ultimately be applicable to geofencing other types of prespecified locations to facilitate healthcare research and patient care., (© 2017 American Heart Association, Inc.)

Highly environment-sensitive fluorophores have been desired for many biomedical applications. Because of the noninvasive operation, high sensitivity, and high specificity to the microenvironment change, they can be used as excellent probes for fluorescence sensing/imaging, cell tracking/imaging, molecular imaging for cancer, and so on (i.e., polarity, viscosity, temperature, or pH measurement). In this work, investigations of the switching mechanism of a recently reported near-infrared environment-sensitive fluorophore, ADP(CA)₂, were conducted. Besides, multiple potential biomedical applications of this switchable fluorescent probe have been demonstrated, including wash-free live-cell fluorescence imaging, in vivo tissue fluorescence imaging, temperature sensing, and ultrasound-switchable fluorescence (USF) imaging. The fluorescence of the ADP(CA)₂ is extremely sensitive to the microenvironment, especially polarity and viscosity. Our investigations showed that the fluorescence of ADP(CA)₂ can be switched on by low polarity, high viscosity, or the presence of protein and surfactants. In wash-free live-cell imaging, the fluorescence of ADP(CA)₂ inside cells was found much brighter than the dye-containing medium and was retained for at least two days. In all of the fluorescence imaging applications conducted in this study, high target-to-noise (>5-fold) was achieved. In addition, a high temperature sensitivity (73-fold per Celsius degree) of ADP(CA)₂-based temperature probes was found in temperature sensing.

Simultaneous imaging of multiple targets (SIMT) in opaque biological tissues is an important goal for molecular imaging in the future. Multi-color fluorescence imaging in deep tissues is a promising technology to reach this goal. In this work, we developed a dual-modality imaging system by combining our recently developed ultrasound-switchable fluorescence (USF) imaging technology with the conventional ultrasound (US) B-mode imaging. This dual-modality system can simultaneously image tissue acoustic structure information and multi-color fluorophores in centimeter-deep tissue with comparable spatial resolutions. To conduct USF imaging on the same plane (i.e., x - z plane) as US imaging, we adopted two 90°-crossed ultrasound transducers with an overlapped focal region, while the US transducer (the third one) was positioned at the center of these two USF transducers. Thus, the axial resolution of USF is close to the lateral resolution, which allows a point-by-point USF scanning on the same plane as the US imaging. Both multi-color USF and ultrasound imaging of a tissue phantom were demonstrated.

Decellularized extracellular matrix (ECM) contains complex tissue-specific components that work in concert to promote tissue repair and constructive remodeling and has been used experimentally and clinically to accelerate epithelial wound repair, leading us to hypothesize that lung-derived ECM could mitigate acute lung injury. To explore the therapeutic potential of ECM for noninvasive delivery to the lung, we decellularized and solubilized porcine lung ECM, then characterized the composition, concentration, particle size and stability of the preparation. The ECM preparation at 3.2 mg/mL with average particle size <3 μm was tested in vitro on human A549 lung epithelial cells exposed to 95% O2 for 24 hours, and in vivo by tracheal instillation or nebulization into the lungs of rats exposed intermittently or continuously to 90% O2 for a cumulative 72 hours. Our results showed that the preparation was enriched in collagen, reduced in glycosaminoglycans, and contained various bioactive molecules. Particle size was concentration-dependent. Compared to the respective controls treated with cell culture medium in vitro or saline in vivo, ECM inhalation normalized cell survival and alveolar morphology, and reduced hyperoxia-induced apoptosis and oxidative damage. This proof-of-concept study established the methodology, feasibility and therapeutic potential of exogenous solubilized ECM for pulmonary cytoprotection, possibly as an adjunct or potentiator of conventional therapy., Competing Interests: The authors have declared that no competing interests exist.

PICKLE (PKL) is an ATP-dependent chromodomain-helicase-DNA-binding domain (CHD3) chromatin remodeling enzyme in Arabidopsis (Arabidopsis thaliana). Previous studies showed that PKL promotes embryonic-to-vegetative transition by inhibiting expression of seed-specific genes during seed germination. The pkl mutants display a low penetrance of the "pickle root" phenotype, with a thick and green primary root that retains embryonic characteristics. The penetrance of this pickle root phenotype in pkl is dramatically increased in gibberellin (GA)-deficient conditions. At adult stages, the pkl mutants are semidwarfs with delayed flowering time, which resemble reduced GA-signaling mutants. These findings suggest that PKL may play a positive role in regulating GA signaling. A recent biochemical analysis further showed that PKL and GA signaling repressors DELLAs antagonistically regulate hypocotyl cell elongation genes by direct protein-protein interaction. To elucidate further the role of PKL in GA signaling and plant development, we studied the genetic interaction between PKL and DELLAs using the hextuple mutant containing pkl and della pentuple (dP) mutations. Here, we show that PKL is required for most of GA-promoted developmental processes, including vegetative growth such as hypocotyl, leaf, and inflorescence stem elongation, and phase transitions such as juvenile-to-adult leaf and vegetative-to-reproductive phase. The removal of all DELLA functions (in the dP background) cannot rescue these phenotypes in pkl RNA-sequencing analysis using the ga1 (a GA-deficient mutant), pkl, and the ga1 pkl double mutant further shows that expression of 80% of GA-responsive genes in seedlings is PKL dependent, including genes that function in cell elongation, cell division, and phase transitions. These results indicate that the CHD3 chromatin remodeler PKL is required for regulating gene expression during most of GA-regulated developmental processes., (© 2017 American Society of Plant Biologists. All Rights Reserved.)

Background: Health literacy has been increasingly recognized as one of the most important social determinants for health. However, an appropriate and comprehensive assessment tool is not available in many Asian countries. This study validates a comprehensive health literacy survey tool European health literacy questionnaire (HLS-EU-Q47) for the general public in several Asian countries., Methods: A cross-sectional survey based on multistage random sampling in the target countries. A total of 10,024 participants aged ≥15 years were recruited during 2013-2014 in Indonesia, Kazakhstan, Malaysia, Myanmar, Taiwan, and Vietnam. The questionnaire was translated into local languages to measure general health literacy and its three domains. To evaluate the validity of the tool in these countries, data were analyzed by confirmatory factor analysis, internal consistency analysis, and regression analysis., Results: The questionnaire was shown to have good construct validity, satisfactory goodness-of-fit of the data to the hypothetical model in three health literacy domains, high internal consistency (Cronbach's alpha >0.90), satisfactory item-scale convergent validity (item-scale correlation ≥0.40), and no floor/ceiling effects in these countries. General health literacy index score was significantly associated with level of education (P from <0.001 to 0.011) and perceived social status (P from <0.001 to 0.016), with evidence of known-group validity., Conclusions: The HLS-EU-Q47 was a satisfactory and comprehensive health literacy survey tool for use in Asia., (Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background: The Pediatric Craniofacial Collaborative Group established the Pediatric Craniofacial Surgery Perioperative Registry to elucidate practices and outcomes in children with craniosynostosis undergoing complex cranial vault reconstruction and inform quality improvement efforts. The aim of this study is to determine perioperative management, outcomes, and complications in children undergoing complex cranial vault reconstruction across North America and to delineate salient features of current practices., Methods: Thirty-one institutions contributed data from June 2012 to September 2015. Data extracted included demographics, perioperative management, length of stay, laboratory results, and blood management techniques employed. Complications and outlier events were described. Outcomes analyzed included total blood donor exposures, intraoperative and perioperative transfusion volumes, and length of stay outcomes., Results: One thousand two hundred twenty-three cases were analyzed: 935 children aged less than or equal to 24 months and 288 children aged more than 24 months. Ninety-five percent of children aged less than or equal to 24 months and 79% of children aged more than 24 months received at least one transfusion. There were no deaths. Notable complications included cardiac arrest, postoperative seizures, unplanned postoperative mechanical ventilation, large-volume transfusion, and unplanned second surgeries. Utilization of blood conservation techniques was highly variable., Conclusions: The authors present a comprehensive description of perioperative management, outcomes, and complications from a large group of North American children undergoing complex cranial vault reconstruction. Transfusion remains the rule for the vast majority of patients. The occurrence of numerous significant complications together with large variability in perioperative management and outcomes suggest targets for improvement.

Hybrid mesoporous materials as carriers for immobilization of D-amino acid oxidase (DAAO) were prepared via three steps: (i) hydrothermal synthesis of nanoporous MCF, SBA-15 and MCM-41 powders, (ii) functionalization with 3-aminopropyltriethoxysilane (APTES) by post-synthesis grafting; and (iii) activation with glutardialdehyde. The resulting mesostructured solids were characterized by various techniques: XRD, IR, TGA-DTA and N2 adsorption–desorption (BET). The characterization results indicated that these materials still maintained their structure after functionalization. IR data and TGA-DTA analysis demonstrated the existence of amine functional groups on the surface of APTES-functionalized samples. The DAAO immobilized on these materials exhibited higher catalytic activity and stability of enzyme for conversion of cephalosporin C (CPC) as compared to those of the non-functionalized ones. The catalytic activity and stability of enzyme decreased in the order MCF > SBA-15 > MCM-41.

Background: Heterophyidiasis is now a major public health threat in many tropical countries. Species in the trematode family Heterophyidae infecting humans include Centrocestus formosanus, Haplorchis pumilio, H. taichui, H. yokogawai, Procerovum varium and Stellantchasmus falcatus. For molecular phylogenetic and systematic studies on trematodes, we need more prospective markers for taxonomic identification and classification. This study provides near-complete ribosomal transcription units (rTU) from Haplorchis pumilio and H. taichui and demonstrates the use of 28S rDNA sequences for identification and phylogenetic analysis., Results: The near-complete ribosomal transcription units (rTU), consisting of 18S, ITS1, 5.8S, ITS2 and 28S rRNA genes and spacers, from H. pumilio and H. taichui from human hosts in Vietnam, were determined and annotated. Sequence analysis revealed tandem repetitive elements in ITS1 in H. pumilio and in ITS2 in H. taichui. A phylogenetic tree inferred from 28S rDNA sequences of 40 trematode strains/species, including 14 Vietnamese heterophyid individuals, clearly confirmed the status of each of the Vietnamese species: Centrocestus formosanus, Haplorchis pumilio, H. taichui, H. yokogawai, Procerovum varium and Stellantchasmus falcatus. However, the family Heterophyidae was clearly not monophyletic, with some genera apparently allied with other families within the superfamily Opisthorchioidea (i.e. Cryptogonimidae and Opisthorchiidae). These families and their constituent genera require substantial re-evaluation using a combination of morphological and molecular data. Our new molecular data will assist in such studies., Conclusions: The 28S rDNA sequences are conserved among individuals within a species but varied between genera. Based on analysis of 40 28S rDNA sequences representing 19 species in the superfamily Opisthorchioidea and an outgroup taxon (Alaria alata, family Diplostomidae), six common human pathogenic heterophyids were identified and clearly resolved. The phylogenetic tree inferred from these sequences again confirmed anomalies in molecular placement of some members of the family Heterophyidae and demonstrates the need for reappraisal of the entire superfamily Opisthorchioidea. The new sequences provided here supplement those already available in public databases and add to the array of molecular tools that can be used for the diagnosis of heterophyid species in human and animal infections.

Next generation sequencing technologies have provided numerous opportunities for application in the study of whole plant genomes. In this study, we present the sequencing and bioinformatic analyses of five typical rice landraces including three indica and two japonica with potential blast resistance. A total of 688.4 million 100 bp paired-end reads have yielded approximately 30-fold coverage to compare with the Nipponbare reference genome. Among them, a small number of reads were mapped to both chromosomes and organellar genomes. Over two million and eight hundred thousand single nucleotide polymorphisms (SNPs) and insertions and deletions (InDels) in indica and japonica lines have been determined, which potentially have significant impacts on multiple transcripts of genes. SNP deserts, contiguous SNP-low regions, were found on chromosomes 1, 4, and 5 of all genomes of rice examined. Based on the distribution of SNPs per 100 kilobase pairs, the phylogenetic relationships among the landraces have been constructed. This is the first step towards revealing several salient features of rice genomes in Vietnam and providing significant information resources to further marker-assisted selection (MAS) in rice breeding programs., Competing Interests: The authors declare that they have no competing interests.

The feeding of alcohol orally (Lieber-DeCarli diet) to rats has been shown to cause declines in mitochondrial respiration (state III), decreased expression of respiratory complexes, and decreased respiratory control ratios (RCR) in liver mitochondria. These declines and other mitochondrial alterations have led to the hypothesis that alcohol feeding causes "mitochondrial dysfunction" in the liver. If oral alcohol feeding leads to mitochondrial dysfunction, one would predict that increasing alcohol delivery by intragastric (IG) alcohol feeding to rats would cause greater declines in mitochondrial bioenergetics in the liver. In this study, we examined the mitochondrial alterations that occur in rats fed alcohol both orally and intragastrically. Oral alcohol feeding decreased glutamate/malate-, acetaldehyde- and succinate-driven state III respiration, RCR, and expression of respiratory complexes (I, III, IV, V) in liver mitochondria, in agreement with previous results. IG alcohol feeding, on the other hand, caused a slight increase in glutamate/malate-driven respiration, and significantly increased acetaldehyde-driven respiration in liver mitochondria. IG feeding also caused liver mitochondria to experience a decline in succinate-driven respiration, but these decreases were smaller than those observed with oral alcohol feeding. Surprisingly, oral and IG alcohol feeding to rats increased mitochondrial respiration using other substrates, including glycerol-3-phosphate (which delivers electrons from cytoplasmic NADH to mitochondria) and octanoate (a substrate for beta-oxidation). The enhancement of glycerol-3-phosphate- and octanoate-driven respiration suggests that liver mitochondria remodeled in response to alcohol feeding. In support of this notion, we observed that IG alcohol feeding also increased expression of mitochondrial glycerol phosphate dehydrogenase-2 (GPD2), transcription factor A (TFAM), and increased mitochondrial NAD + -NADH and NADP + -NADPH levels in the liver. Our findings suggest that mitochondrial dysfunction represents an incomplete picture of mitochondrial dynamics that occur in the liver following alcohol feeding. While alcohol feeding causes some mitochondrial dysfunction (i.e. succinate-driven respiration), our work suggests that the major consequence of alcohol feeding is mitochondrial remodeling in the liver as an adaptation. This mitochondrial remodeling may play an important role in the enhanced alcohol metabolism and other adaptations in the liver that develop with alcohol intake., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Neurodegenerative disorders (NDs) are typically referred to Alzheimer's disease, Parkinson's diseases, amyotrophic lateral sclerosis and prion disease. These are commonly debilitating and, unfortunately, have few therapeutic options., Objective: In this review, we describe some emerging advances in nanoengineering strategies for the treatment of NDs. One of the main difficulties in fighting against NDs is to overcome the shielding of blood-brain barrier (BBB), which greatly limits the penetration of various therapeutic drugs, which sometimes leads to severe side effects. Nanotechnology, by engineering materials of a size scale usually within 1-100 nm, fortunately offers an alternative approach for novel, promising and innovative solutions. Nanoparticles are capable of not only penetrating the BBB but also releasing active ingredients at a specific site due to its surface functionalization. Therefore, nanoengineered delivery systems potentially facilitate the targeted delivery of neuronal therapeutic drugs and genes to the central nervous system. Furthermore, recently developed nanomaterials are considered as therapeutic agents themselves since they exhibit important roles in promoting the protection of healthy neurons or the regeneration of neurons to repair damaged tissues., Conclusion: There have been a variety of innovative approaches to designing therapeutic nanoparticles for NDs, and each has been associated with certain pros and cons., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The melanocortin neuronal system, which consists of hypothalamic proopiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, is a leptin target that regulates energy balance and metabolism, but studies in humans are limited by a lack of reliable biomarkers to assess brain melanocortin activity. The objective of this study was to measure the POMC prohormone and its processed peptide, β-endorphin (β-EP), in cerebrospinal fluid (CSF) and AgRP in CSF and plasma after calorie restriction to validate their utility as biomarkers of brain melanocortin activity. CSF and plasma were obtained from 10 lean and obese subjects after fasting (40 h) and refeeding (24 h), and from 8 obese subjects before and after 6 wk of dieting (800 kcal/day) to assess changes in neuropeptide and hormone levels. After fasting, plasma leptin decreased to 35%, and AgRP increased to 153% of baseline. During refeeding, AgRP declined as leptin increased; CSF β-EP increased, but POMC did not change. Relative changes in plasma and CSF leptin were blunted in obese subjects. After dieting, plasma and CSF leptin decreased to 46% and 70% of baseline, CSF POMC and β-EP decreased, and plasma AgRP increased. At baseline, AgRP correlated negatively with insulin and homeostasis model assessment (HOMA-IR), and positively with the Matsuda index. Thus, following chronic calorie restriction, POMC and β-EP declined in CSF, whereas acutely, only β-EP changed. Plasma AgRP, however, increased after both acute and chronic calorie restriction. These results support the use of CSF POMC and plasma AgRP as biomarkers of hypothalamic melanocortin activity and provide evidence linking AgRP to insulin sensitivity., (Copyright © 2017 the American Physiological Society.)

Background: Atrial refractoriness may be an important determinant of atrial fibrillation (AF) risk, but its measurement is not clinically accessible. Because the QT interval predicts incident AF and the atrium and ventricle share repolarizing ion currents, we investigated the association between an individual's QT interval and atrial effective refractory period (AERP)., Methods: In paroxysmal AF patients presenting for catheter ablation, the QT interval was measured from the surface 12-lead electrocardiogram. The AERP was defined as the longest S1-S2 coupling interval without atrial capture using a 600-ms drive cycle length., Results: In 28 patients, there was a positive correlation between QTc and mean AERP. After multivariate adjustment, a 1-ms increase in QTc predicted a 0.70-ms increase in AERP., Conclusions: The QTc interval reflects the AERP, suggesting that the QTc interval may be used as a marker of atrial refractoriness relevant to assessing AF risk and mechanism-specific therapeutic strategies., (© 2016 Wiley Periodicals, Inc.)

Aspergillus oryzae is a safe mold widely used in food industry. It is also considered as a microbial cell factory for production of recombinant proteins and enzymes. Currently, genetic manipulation of filamentous fungi is achieved via Agrobacterium tumefaciens-mediated transformation methods usually employing antibiotic resistance markers. These methods are hardly usable for A. oryzae due to its strong resistance to the common antifungal compounds used for fungal transformation. In this study, we have constructed two binary vectors carrying the pyrG gene from A. oryzae as a biochemical marker than an antibiotic resistance marker, and an expression cassette for GFP or DsRed reporter gene under control of the constitutive gpdA promoter from Aspergillus nidulans. All components of these vectors are changeable to generate new versions for specific research purposes. The developed vectors are fully functional for heterologous expression of the GFP and DsRed fluorescent proteins in the uridine/uracil auxotrophic A. oryzae strain. Our study provides a new approach for A. oryzae transformation using pyrG as the selectable auxotrophic marker, A. tumefaciens as the DNA transfer tool and fungal spores as the transformation material. The binary vectors constructed can be used for gene expression studies in this industrially important filamentous fungus.

For many years, investigators have sought after high-resolution fluorescence imaging in centimeter-deep tissue because many interesting in vivo phenomena-such as the presence of immune system cells, tumor angiogenesis, and metastasis-may be located deep in tissue. Previously, we developed a new imaging technique to achieve high spatial resolution in sub-centimeter deep tissue phantoms named continuous-wave ultrasound-switchable fluorescence (CW-USF). The principle is to use a focused ultrasound wave to externally and locally switch on and off the fluorophore emission from a small volume (close to ultrasound focal volume). By making improvements in three aspects of this technique: excellent near-infrared USF contrast agents, a sensitive frequency-domain USF imaging system, and an effective signal processing algorithm, for the first time this study has achieved high spatial resolution (~ 900 μm) in 3-centimeter-deep tissue phantoms with high signal-to-noise ratio (SNR) and high sensitivity (3.4 picomoles of fluorophore in a volume of 68 nanoliters can be detected). We have achieved these results in both tissue-mimic phantoms and porcine muscle tissues. We have also demonstrated multi-color USF to image and distinguish two fluorophores with different wavelengths, which might be very useful for simultaneously imaging of multiple targets and observing their interactions in the future. This work has opened the door for future studies of high-resolution centimeter-deep tissue fluorescence imaging., Competing Interests: The authors have declared that no competing interests exist.

Background: Smartphones are increasingly integrated into everyday life, but frequency of use has not yet been objectively measured and compared to demographics, health information, and in particular, sleep quality., Aims: The aim of this study was to characterize smartphone use by measuring screen-time directly, determine factors that are associated with increased screen-time, and to test the hypothesis that increased screen-time is associated with poor sleep., Methods: We performed a cross-sectional analysis in a subset of 653 participants enrolled in the Health eHeart Study, an internet-based longitudinal cohort study open to any interested adult (≥ 18 years). Smartphone screen-time (the number of minutes in each hour the screen was on) was measured continuously via smartphone application. For each participant, total and average screen-time were computed over 30-day windows. Average screen-time specifically during self-reported bedtime hours and sleeping period was also computed. Demographics, medical information, and sleep habits (Pittsburgh Sleep Quality Index-PSQI) were obtained by survey. Linear regression was used to obtain effect estimates., Results: Total screen-time over 30 days was a median 38.4 hours (IQR 21.4 to 61.3) and average screen-time over 30 days was a median 3.7 minutes per hour (IQR 2.2 to 5.5). Younger age, self-reported race/ethnicity of Black and "Other" were associated with longer average screen-time after adjustment for potential confounders. Longer average screen-time was associated with shorter sleep duration and worse sleep-efficiency. Longer average screen-times during bedtime and the sleeping period were associated with poor sleep quality, decreased sleep efficiency, and longer sleep onset latency., Conclusions: These findings on actual smartphone screen-time build upon prior work based on self-report and confirm that adults spend a substantial amount of time using their smartphones. Screen-time differs across age and race, but is similar across socio-economic strata suggesting that cultural factors may drive smartphone use. Screen-time is associated with poor sleep. These findings cannot support conclusions on causation. Effect-cause remains a possibility: poor sleep may lead to increased screen-time. However, exposure to smartphone screens, particularly around bedtime, may negatively impact sleep., Competing Interests: LK and STM are employees of Ginger.io Incorporated. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The complete mitochondrial (mt) genome of the trematode Echinochasmus japonicus Tanabe, 1926 was fully determined and annotated. The circular mt molecule of this species is 15,865bp in length, containing 12 protein-coding genes (arranged in the following order: cox3-cob-nad4L-nad4-atp6-nad2-nad1-nad3-cox1-cox2-nad6-nad5), two ribosomal RNA genes (rrnL and rrnS) and 22 transfer RNA genes (trnH; trnQ; trnF; trnM; trnV; trnA; trnD; trnN; trnP; trnI; trnK; trnS 1(AGN) ; trnW; trnT; trnC; trnL 1(CUN) ; trnS 2(UCN) ; trnL 2(UUN) ; trnG; and trnE). The atp8 gene is absent. The 3' end of nad4L overlaps the 5' end of nad4 by 40bp. An array of eight identical tandem repeats (240bp each) was found between trnG and trnE in the long non-coding region of the individual worm sequenced. Numbers of these repeats varied among E. japonicus samples. Phylogenetic analysis of concatenated mt protein sequences of 40 trematode species/strains supports the elevation of Echinochasminae Odhner, 1910 to family rank, close to the families Echinostomatidae and Fasciolidae. As echinochasmid and echinostomatid species can parasitize humans, the future characterization of additional mt genomes is needed for development of mt markers for identification and phylogenetic, population, epidemiological and hybridization studies., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Recently, we developed a new technology, ultrasound-switchable fluorescence (USF), for high-resolution imaging in centimeter-deep tissues via fluorescence contrast. The success of USF imaging highly relies on excellent contrast agents. ICG-encapsulated poly(N-isopropylacrylamide) nanoparticles (ICG-NPs) are one of the families of the most successful near-infrared (NIR) USF contrast agents. However, the first-generation ICG-NPs have a short shelf life (<1 month). This work significantly increases the shelf life of the new-generation ICG-NPs (>6 months). In addition, we have conjugated hydroxyl or carboxyl function groups on the ICG-NPs for future molecular targeting. Finally, we have demonstrated the effect of temperature-switching threshold (T th ) and the background temperature (T BG ) on the quality of USF images. We estimated that the T th of the ICG-NPs should be controlled at ~38-40 °C (slightly above the body temperature of 37 °C) for future in vivo USF imaging. Addressing these challenges further reduces the application barriers of USF imaging.

Biomimicking hydrogel-based cell culture platforms with physiologically relevant stiffness are powerful tools to modulate the behaviors of stem cells. Herein, the use of fibronectin-conjugated polyacrylamide (PAA) hydrogel biointerface is exploited to modulate the intracellular oxidative stress of human bone marrow derived mesenchymal stem cells (MSCs). We show that compliant culture surface with kPa range matrix stiffness can augment the expression level of reactive oxygen species (ROS) in MSCs by approximately 2-4 fold compared with cells grown on conventional FN coated glass control surface in a noncytotoxic manner. Via an unbiased proteomics approach and mechanistic studies, we show that the secretion level of a sub series of "mechano-sensitive" chemokines and trophic factors is heavily dependent on the PAA matrix stiffness mediated ROS level. Importantly, the secretome harvested from the cells that were grown on the PAA hydrogel was found to enhance wound healing in both in vitro and in vivo full thickness mouse excisional wound model. The devised "soft approach" to induce oxidative stress in MSCs is posited to pave the way for novel cell-free therapeutic interventions targeting a wide variety of diseases and to foster functional tissue repair.

Intraoral ultrasonography uses high-frequency mechanical waves to study dento-periodontium. Besides the advantages of portability and cost-effectiveness, ultrasound technique has no ionizing radiation. Previous studies employed a single transducer or an array of transducer elements, and focused on enamel thickness and distance measurement. This study used a phased array system with a 128-element array transducer to image dento-periodontal tissues. We studied two porcine lower incisors from a 6-month-old piglet using 20-MHz ultrasound. The high-resolution ultrasonographs clearly showed the cross-sectional morphological images of the hard and soft tissues. The investigation used an integration of waveform analysis, travel-time calculation, and wavefield simulation to reveal the nature of the ultrasound data, which makes the study novel. With the assistance of time-distance radio-frequency records, we robustly justified the enamel-dentin interface, dentin-pulp interface, and the cemento-enamel junction. The alveolar crest level, the location of cemento-enamel junction, and the thickness of alveolar crest were measured from the images and compared favorably with those from the cone beam computed tomography with less than 10% difference. This preliminary and fundamental study has reinforced the conclusions from previous studies, that ultrasonography has great potential to become a non-invasive diagnostic imaging tool for quantitative assessment of periodontal structures and better delivery of oral care.

Introduction: The aim of this study was to identify the genetic characteristics and molecular genotyping of duck hepatitis A virus (DHAV) isolated in Vietnam during 2009-2013., Methodology: Thirty duckling livers from outbreaks between 2009 and 2013 in seven provinces were collected and identified by polymerase chain reaction (PCR). Then, VP1 genes of eleven positive samples and two attenuated vaccine strains were sequenced and analyzed., Results: Genotypic and phylogenetic analyses indicated that the 13 Vietnamese isolates were classified into two genotypes, DHAV-1 and DHAV-3. The rate of identity and homology was 91%-100% between the 10 Vietnamese and 26 global strains of DHAV-3, and 92%-100% between 3 Vietnamese and 16 strains of DHAV-1. Between the DHAV-3 and DHAV-1 strains, the divergence reached 30%. At the C-terminal of VP1 for the different strains, a hypervariable region was observed, and notably, six of the Vietnamese DHAV-3 strains in this study showed four consistent differences (at positions T184M, Q200H, K207N, and K214R) within this group that were distinct from all other DHAV-3 strains., Conclusions: This is the first report of molecular characterization of DHAVs in Vietnam. At least two genotypes were identified, DHAV-1 and DHAV-3, with diversified clades within and between genotypes. DHAV-3 seemed to be dominant in Vietnam.

Atrial fibrillation (AF) is likely secondary to multiple different pathophysiological mechanisms that are increasingly but incompletely understood. Motivated by the hypothesis that 3 previously described electrocardiographic predictors of AF identify distinct AF mechanisms, we sought to determine if these electrocardiographic findings independently predict incident disease. Among Cardiovascular Health Study participants without prevalent AF, we determined whether left anterior fascicular block (LAFB), a prolonged QTC, and atrial premature complexes (APCs) each predicted AF after adjusting for each other. We then calculated the attributable risk in the exposed for each electrocardiographic marker. LAFB and QTC intervals were assessed on baseline 12-lead electrocardiogram (n = 4,696). APC count was determined using 24-hour Holter recordings obtained in a random subsample (n = 1,234). After adjusting for potential confounders and each electrocardiographic marker, LAFB (hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.1 to 3.9, p = 0.023), a prolonged QTC (HR 2.5, 95% CI 1.4 to 4.3, p = 0.002), and every doubling of APC count (HR 1.2, 95% CI 1.1 to 1.3, p <0.001) each remained independently predictive of incident AF. The attributable risk of AF in the exposed was 35% (95% CI 13% to 52%) for LAFB, 25% (95% CI 0.6% to 44%) for a prolonged QTC, and 34% (95% CI 26% to 42%) for APCs. In conclusion, in a community-based cohort, 3 previously established electrocardiogram-derived AF predictors were each independently associated with incident AF, suggesting that they may represent distinct mechanisms underlying the disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Keloids represent a challenging problem. Surgical excision remains the definitive treatment for immediate lesion debulking, but recurrence rates are reported to be 45 to 100 percent. The authors present a staged reconstructive approach using a dermal regeneration substrate and epidermal grafting to minimize recurrence and donor-site morbidity., Methods: Keloids were completely excised down to normal subcutaneous tissue or perichondrium. A bilaminar dermal regeneration matrix was approximated to the entire wound, with the silicone lamina oriented superficially. Reconstruction was delayed for at least 21 days to allow for neodermal ingrowth. The silicone lamina was then removed, and an epidermal skin graft was harvested from the thigh and secured to the neodermis with nonocclusive dressing. Reconstructed defects and donor sites were assessed for recurrence of keloids and scar appearance., Results: Five patients underwent treatment; two had keloids involving the superior helix of the ear (average area, 2.6 cm), two had keloids involving the chest (average area, 28 cm), and one had a keloid in the pubic region (area, 10 cm). All had failed at least one previous treatment with direct excision and steroid injections. Mean follow-up was 48.8 weeks (range, 38 to 60 weeks). Average time to complete wound epithelialization was 5.5 weeks. There were no infections or cellulitis. All reconstructed defects were aesthetically acceptable and remained flat without significant widening. There were no long-term complaints of pruritus or pain and there was no evidence of donor-site scarring., Conclusions: Epidermal grafting provides significant advantages when used with a dermal regeneration matrix. This approach obviates reliance on skin creep and flap undermining to achieve primary closure. Exclusion of dermis and significant extracellular matrix components limits contracture, further facilitating tension-free wound healing. Scarring response within the donor site and graft is also minimized., Clinical Question/level of Evidence: Therapeutic, IV.

Vapochromic behavior is employed to selectively monitor the vapor changes in surrounding environment, particularly for toxic gas leaking and floating detection. Thus, sensitive trapping and accurate response to different toxic vapors are critical factors in vapochromic sensing. In this work, a self-assembled hybrid that consists of fluorescent organic octahedron encapsulated by metal-organic polyhedron (MOP) is reported. The fluorescent octahedron is used as a responsive sensor to probe various solvent vapors, while the MOP is employed as a protector to prevent the corrosion of solvents to the organic octahedron. The hybrid exhibits remarkable vapochromic behavior to different solvents, and shows the highest selectivity and sensitivity specifically to acetone. In addition, acetone vapor under different conditions is utilized for further studying the response mechanism of the hybrid. This work presents a promising vapochromic sensor with good stability, selectivity, and sensitivity. The study is expected to open up the applicability of MOP-based hybrids for specific molecular capture, interim storage, controlled release, and advanced sensing., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Sum frequency generation vibrational spectroscopy (SFG) was utilized to investigate the interaction between PAP248-286 and the two lipid bilayer systems. The present study also provides spectroscopic evidence to confirm that, although PAP248-286 is unable to penetrate into the hydrophobic core of the lipid bilayers, it is capable of interacting more intimately with the fluid-phase POPG/POPC than with the gel-phase DPPG/DPPC lipid bilayer. The helical structure content of lipid-bound PAP248-286 was also observed to be high, in contrast to the results previously reported using nuclear magnetic resonance (NMR). Collectively, our SFG data suggest that lipid-bound PAP248-286 actually resembles its structure in 50 % 2,2,2-trifluoroethanol better than the structure when the peptide binds to SDS micelles. This present study questions the use of SDS micelles as the model membrane for NMR studies of PAP248-286 due to its protein denaturing activity.

The Gibbs adsorption isotherm (GAI) has been considered as the foundation of surfactant adsorption studies for over a century; however, its application in determining the limiting surface excess has recently been intensively discussed, with contradictory experimental evidence either supporting or refuting the theory. The available arguments are based on monolayer adsorption models. In this paper, we experimentally and intellectually propose and validate the contribution of sub-monolayer adsorption to the GAI paradox. We utilize a powerful intrinsically surface-sensitive technique, vibrational sum-frequency generation spectroscopy (SFG), complementing with conventional tensiometric measurements to address these controversies both quantitatively and qualitatively. Our SFG results revealed that the precipitous decrease in surface tension directly corresponds to surface occupancy by adsorbates. In addition, the Gibbs analysis was successfully applied to the soluble monolayer of a surface-active alcohol to full saturation. However, the full saturation of the topmost monolayer does not necessarily mean that the surface adsorption was completed because the adsorption was observed to continuously occur in the sub-monolayer region soon after the topmost monolayer became saturated. Nonetheless, the Gibbs isotherm failed to account for the excess of alcohol adsorbed in this sub-monolayer region. This new concept of surface excess must therefore be treated thermodynamically.

Our goals were to develop and establish nanoparticle (NP)-facilitated inhalational gene delivery, and to validate its biomedical application by testing the hypothesis that targeted upregulation of pulmonary erythropoietin receptor (EpoR) expression protects against lung injury. Poly-lactic-co-glycolic acid (PLGA) NPs encapsulating various tracers were characterized and nebulizated into rat lungs. Widespread NP uptake and distribution within alveolar cells were visualized by magnetic resonance imaging, and fluorescent and electron microscopy. Inhalation of nebulized NPs bearing EpoR cDNA upregulated pulmonary EpoR expression and downstream signal transduction (ERK1/2 and STAT5 phosphorylation) in rats for up to 21 days, and attenuated hyperoxia-induced damage in lung tissue based on apoptosis, oxidative damage of DNA, protein and lipid, tissue edema, and alveolar morphology compared to vector-treated control animals. These results establish the feasibility and therapeutic efficacy of NP-facilitated cDNA delivery to the lung, and demonstrate that targeted pulmonary EpoR upregulation mitigates acute oxidative lung damage., From the Clinical Editor: Acute lung injury often results in significant morbidity and mortality, and current therapeutic modalities have proven to be ineffective. In this article, the authors developed nanocarrier based gene therapy in an attempt to upregulate the expression of pulmonary erythropoietin receptor in an animal model. Inhalation delivery resulted in reduction of lung damage., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: To investigate the specific carbohydrate diet (SCD) as nutritional therapy for maintenance of remission in pediatric Crohn's disease (CD)., Methods: Retrospective chart review was conducted in 11 pediatric patients with CD who initiated the SCD as therapy at time of diagnosis or flare. Two groups defined as SCD simple (diet alone, antibiotics or 5-ASA) or SCD with immunomodulators (corticosteroids and/or stable thiopurine dosing) were followed for one year and compared on disease characteristics, laboratory values and anthropometrics., Results: The mean age at start of the SCD was 11.8 ± 3.0 years (range 6.6-17.6 years) with five patients starting the SCD within 5 wk of diagnosis. Three patients maintained a strict SCD diet for the study period and the mean time for liberalization was 7.7 ± 4.0 mo (range 1-12) for the remaining patients. In both groups, hematocrit, albumin and ESR values improved while on strict SCD and appeared stable after liberalization (P-value 0.006, 0.002, 0.002 respectively). The majority of children gained in weight and height percentile while on strict SCD, with small loss in weight percentile documented with liberalization., Conclusion: Disease control may be attainable with the SCD in pediatric CD. Further studies are needed to assess adherence, impact on mucosal healing and growth.

Aim: Direct pulp capping is the treatment of an exposed vital pulp with a dental material to facilitate the formation of reparative dentin and maintenance of vital pulp. A bioengineered drug delivery vehicle has the potential to increase the success rate of pulp capping. The aim of this study was to develop an injectable and light-curing drug delivery vehicle for endodontic treatment including direct pulp capping., Methods: Polyethylene glycol-maleate-citrate (PEGMC) hydrogel was synthesized as a drug delivery vehicle that is composed of PEGMC (45% w/v), acrylic acid (AA) (5% w/v), 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) (0.1% w/v), and deionized water. The association between prehydrogel-solution volume and visible light-curing was examined. The cytotoxicity of the hydrogel was tested using L929 cells in a cell culture system. Ca(2+) release from the hydrogel was determined using calcium hydroxide as the incorporated medicine., Results: The results showed that the light-curing time for hydrogel is comparable to composite resin. The hydrogel had cell toxicity similar to adhesive systems. Moreover, controlled Ca(2+) release was obtained from the calcium hydroxide incorporated hydrogel., Conclusions: The data suggest that hydrogel should be explored further as a promising drug delivery vehicle for vital pulp therapy and regenerative endodontics., (© 2014 Wiley Publishing Asia Pty Ltd.)

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon, benign localized fibrotic lesion. Historically, PASH has been difficult to differentiate from angiosarcoma. This difficulty has led to recommendations of surgical excision. We sought to identify the incidence of upgraded pathology to atypia or malignancy on surgical excisional biopsy after identification of PASH on core needle biopsy (CNB). A 5-year retrospective review at a single institution was conducted including all cases of PASH confirmed on CNB. The data set was divided into patients who underwent excisional biopsy and those followed only by imaging. Primary end points included the incidence of subsequent malignancy or high-risk pathology on histologic analysis or the presentation of suspicious imaging. Thirty-seven patients were reviewed, 19 (51.4%) underwent surgical excision and 18 (48.6%) were followed with imaging alone. A palpable mass was noted in 36.8 per cent of patients in the excisional group versus 5.6 per cent in the imaging group (P = 0.02). The median follow-up for the excisional and imaging groups were 43 and 35 months, respectively (P = 0.85). The 95 per cent confidence interval for the presence of malignancy was 0 to 9.4 per cent. Although further characterization of PASH is needed, our data support using CNB with follow-up imaging as a safe alternative to excisional biopsy in the absence of symptoms or other clinical factors. However, further research in this area is needed.

Nanoparticles for a specific delivery are likely to be designed for cancer therapeutic effectiveness and improvement. In this study, a fucoidan-oleic acid conjugate was prepared and investigated in terms of loading capacity for poorly water-soluble anti-cancer drugs to maximize effectiveness of the treatment. Fucoidan was used as a hydrophilic portion of an amphiphilic structure for improving cancer therapeutic effects. Paclitaxel and curcumin were chosen as other model drugs loaded in the conjugates. The results showed that self-assembled nanoparticles with different sizes and morphologies could be prepared with two different concentrations of oleic acid as hydrophobic portion. Moreover, loading efficiency and release patterns of these drugs were mainly dependent on the hydrophobic interaction between drugs and oleic acid. It was also revealed that fucoidan and curcumin were released higher at pH 4.5 than at the physiological condition (pH 7.4), thus, facilitating the delivery and maximizing effects of the anticancer agents on cancer cells. On the contrary, paclitaxel from fucoidan nanoparticles was released faster at pH 7.4. The exploration of fucoidan-oleic acid conjugate could be considered as promising nanomedicines for cancer therapeutics.

A mobile, affordable product that provides clinicians and patients with comprehensive asthma assessment is needed to improve asthma control. Our solution is an integrated system consisting of a portable, inexpensive, easy-to-use spirometer and a mobile application that communicates wirelessly with the spirometer. Results demonstrated that the wireless asthma management solution meets recommended American Thoracic Society (ATS) and European Respiratory Society (ERS) standards. The device is expected to empower patients to accurately self-assess their asthma for better self-management at home, work, or leisure.

A versatile, flexible piezoceramic array has been developed for a variety of ultrasound applications. The transducer can be configured as a linear or curvilinear transducer array, or mounted directly onto the body as a patch or wearable device. Results using a prototype 16-element array demonstrated equivalence to commercial linear array probes in accuracy of vessel diameter measurements in vascular phantoms. The ability to view needle insertion for peripherally inserted central catheter (PICC) procedures was also demonstrated. Opportunities for wearable ultrasound devices include point-of-care imaging, combat casualty care, ultrasound therapy, patient monitoring, and personal health.

Over the last 30 years, nanoparticle-based medicine has received tremendous attention due to its advances with smart therapeutics and less toxicity. Few nanomedicine products have been approved for commercial use in the clinic (such as Doxil(®), Ambraxane(®)..). Nanomedicine research is still at its early stage and the preparation of nanoparticles must be carefully considered. Systems involving further increased supersaturation, either via solvent evaporation, temperature reduction or anti-solvent mixture, were suggested to be capable of inducing nanoprecipitation (NPT). Since this technique is straight-forward, fast and easy to duplicate in practice, it is highly preferred and recommended. In this review, the process of NTP was described and discussed in detail. Factors that affect the encapsulation efficiency, the nanoparticle size, the morphology and the stability of nanoparticles prepared by NTP were described. This process is one of the most preferable processes for preparing solid nano-protein due to their elegant techniques that preserve the bioactivity of proteins. Although the production of nanoparticles by this process has not been applied in the pharmaceutical industry due to the organic solvent issue, the production equipment for large-scale has been marketed.

Dexamethasone-releasing poly(lactic-co-glycolic acid) (PLGA) microparticles were formulated using a solvent displacement technique with the addition of distillation aiming to increase drug delivery lifetime. Two PLGA copolymer ratios (50:50 and 75:25) were used to determine the influence of lactic acid and glycolic acid ratio on microparticle characteristics. The addition of distillation significantly slows the release of dexamethasone compared to traditional solvent removal via evaporation while still maintaining a therapeutic dosage. Microparticles formulated with PLGA 50:50 controllably release dexamethasone up to one year and 75:25 release up to two years in-vitro. The ratio of lactic acid to glycolic acid plays a significant role in microparticle stability, drug loading efficiency, and thermal properties. In all, this formulation technique offers new prospects for inflammation suppression in pediatric vascular and airway diseases., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Toxocara canis of canids is a parasitic nematode (ascaridoid) that infects humans and other hosts, causing different forms of toxocariasis. This species of Toxocara appears to be the most important cause of human disease, likely followed by Toxocara cati from felids. Although some studies from Malaysia and China have shown that cats can harbor another congener, T. malaysiensis, no information is available about this parasite for other countries. Moreover, the zoonotic potential of this parasite is unknown at this point. In the present study, we conducted the first investigation of domestic dogs and cats for Toxocara in Vietnam using molecular tools. Toxocara malaysiensis was identified as a common ascaridoid of domestic cats (in the absence of T. cati), and T. canis was commonly found in dogs. Together with findings from previous studies, the present results emphasize the need to explore the significance and zoonotic potential of T. malaysiensis in Vietnam and other countries where this parasite is endemic and prevalent in cats., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Together with the simultaneous development of nanomaterials and molecular biology, the bionano interface brings about various applications of hybrid nanoparticles in nanomedicine. The hybrid nanoparticles not only present properties of the individual components but also show synergistic effects for specialized applications. Thus, the development of advanced hybrid nanoparticles for targeted and on-demand diagnostics and therapeutics of diseases has rapidly become a hot research topic in nanomedicine. The research focus is to fabricate novel classes of programmable hybrid nanoparticles that are precisely engineered to maximize drug concentrations in diseased cells, leading to enhanced efficacy and reduced side effects of chemotherapy for the disease treatment. In particular, the hybrid nanoparticle platforms can simultaneously target diseased cells, enable the location to be imaged by optical methods, and release therapeutic drugs to the diseased cells by command. This Account specially discusses the rational fabrication of integrated hybrid nanoparticles and their applications in diagnostics and therapeutics. For diagnostics applications, hybrid nanoparticles can be utilized as imaging agents that enable detailed visualization at the molecular level. By the use of suitable targeting ligands incorporated on the nanoparticles, targeted optical imaging may be feasible with improved performance. Novel imaging techniques such as multiphoton excitation and photoacoustic imaging using near-infrared light have been developed using the intrinsic properties of particular nanoparticles. The use of longer-wavelength excitation sources allows deeper penetration into the human body for disease diagnostics and at the same time reduces the adverse effects on normal tissues. Furthermore, multimodal imaging techniques have been achieved by combining several types of components in nanoparticles, offering higher accuracy and better spatial views, with the aim of detecting life-threatening diseases before symptoms appear. For therapeutics applications, various nanoparticle-based treatment methods such as photodynamic therapy, drug delivery, and gene delivery have been developed. The intrinsic ability of organic nanoparticles to generate reactive oxygen species has been utilized for photodynamic therapy, and mesoporous silica nanoparticles have been widely used for drug loading and controlled delivery. Herein, the development of controlled-release systems that can specifically deliver drug molecules to target cells and release then upon triggering is highlighted. By control of the release of loaded drug molecules at precise sites (e.g., cancer cells or malignant tumors), side effects of the drugs are minimized. This approach provides better control and higher efficacy of drugs in the human body. Future personalized medicine is also feasible through gene delivery methods. Specific DNA/RNA-carrying nanoparticles are able to deliver them to target cells to obtain desired properties. This development may create an evolution in current medicine, leading to more personalized healthcare systems that can reduce the population screening process and also the duration of drug evaluation. Furthermore, nanoparticles can be incorporated with various components that can be used for simultaneous diagnostics and therapeutics. These multifunctional theranostic nanoparticles enable real-time monitoring of treatment process for more efficient therapy.

BOTRYTIS SUSCEPTIBLE1 INTERACTOR (BOI) and its three homologs (BOIs) are RING domain-containing proteins that repress flowering. Here, we investigated how BOIs repress flowering. Genetic analysis of the boiQ quadruple mutant indicates that BOIs repress flowering mainly through FLOWERING LOCUS T (FT). BOIs repress the expression of FT by CONSTANS (CO)-dependent and -independent mechanisms: in the CO-dependent mechanism, BOIs bind to CO, inhibit the targeting of CO to the FT locus, and thus repress the expression of FT; in the CO-independent mechanism, BOIs target the FT locus via a mechanism that requires DELLAs but not CO. This dual repression of FT makes BOIs strong repressors of flowering in both CO-dependent and CO-independent pathways in Arabidopsis thaliana. Our finding that BOIs inhibit CO targeting further suggests that, in addition to modulating CO mRNA expression and CO protein stability, flowering regulation can also modulate the targeting of CO to FT., (Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.)

Three-dimensional (3D) graphene aerogel (GA) has emerged as an outstanding support for metal oxides to enhance the overall energy-storage performance of the resulting hybrid materials. In the current stage of the studies, metals/metal oxides inside GA are in uncrafted geometries. Introducing structure-controlled metal oxides into GA may further push electrochemical properties of metal oxide-GA hybrids. Using rutile SnO2 as an example, we demonstrated here a facile hydrothermal strategy combined with a preconditioning technique named vacuum-assisted impregnation for in situ construction of controlled anisotropic SnO2 heterostructures inside GA. The obtained hybrid material was fully characterized in detail, and its formation mechanism was investigated by monitoring the phase-transformation process. Rational integration of the two advanced structures, anisotropic SnO2 and 3D GA, synergistically led to enhanced lithium-storage properties (1176 mAh/g for the first cycle and 872 mAh/g for the 50th cycle at 100 mA/g) as compared with its two counterparts, namely, rough nanoparticles@3D GA and anisotropic SnO2@2D graphene sheets (618 and 751 mAh/g for the 50th cycle at 100 mA/g, respectively). It was also well-demonstrated that this hybrid material was capable of delivering high specific capacity at rapid charge/discharge cycles (1044 mAh/g at 100 mA/g, 847 mAh/g at 200 mA/g, 698 mAh/g at 500 mA/g, and 584 mAh/g at 1000 mA/g). The in situ integration strategy along with vacuum-assisted impregnation technique presented here shows great potential as a versatile tool for accessing a variety of sophisticated smart structures in the form of anisotropic metals/metal oxides within 3D GA toward useful applications.

Wound healing is usually facilitated by the use of a wound dressing that can be easily applied to cover the wound bed, maintain moisture, and avoid bacterial infection. In order to meet all of these requirements, we developed an in situ forming biodegradable hydrogel (iFBH) system composed of a newly developed combination of biodegradable poly(ethylene glycol) maleate citrate (PEGMC) and poly(ethylene glycol) diacrylate (PEGDA). The in situ forming hydrogel systems are able to conform to the wound shape in order to cover the wound completely and prevent bacterial invasion. A 2(k) factorial analysis was performed to examine the effects of polymer composition on specific properties, including the curing time, Young's modulus, swelling ratio, and degradation rate. An optimized iFBH formulation was achieved from the systematic factorial analysis. Further, in vitro biocompatibility studies using adult human dermal fibroblasts (HDFs) confirmed that the hydrogels and degradation products are not cytotoxic. The iFBH wound dressing was conjugated and functionalized with antimicrobial peptides as well. Evaluation against bacteria both in vitro and in vivo in rats demonstrated that the peptide-incorporated iFBH wound dressing offered excellent bacteria inhibition and promoted wound healing. These studies indicated that our in situ forming antimicrobial biodegradable hydrogel system is a promising candidate for wound treatment., (© 2015 Wiley Periodicals, Inc.)

Amines are one of the common functional groups of interest due to their abundant presence in natural proteins, surfactants and other chemicals. However, their accurate spectral assignment of vibrational modes, critical to interpreting SFG signals for characterizing various bio-interfaces such as protein-membrane interaction and surfactant adsorption, still remains elusive. Herein we present a systematic study to identify and justify the correct peak assignment of the N(+)-H stretching mode at the air-water interface. We used three special surfactants: hexadecylamine (a primary amine without counterions), dodecylamine hydrochloride (a primary amine with counterions) and hexadecyltrimethylammonium bromide as a control (the N(+)-H stretching mode is absent in this quarternary amine). We suppressed the SFG interfacial water signals using saturated NaCl solutions. Our designed experiments resolved the current controversy and concluded that the 3080 cm(-1) peak is from the N(+)-H vibrations, while the 3330 cm(-1) peak is not due to ammonium species but rather originates from the interfacial water vibrational modes or the backbone amide modes.

Improvement in type 2 diabetes after Roux-en-Y gastric bypass (RYGB) has been attributed partly to weight loss, but mechanisms beyond weight loss remain unclear. We performed an ancillary study to the Diabetes Surgery Study to assess changes in incretins, insulin sensitivity, and secretion 1 year after randomization to lifestyle modification and intensive medical management (LS/IMM) alone (n = 34) or in conjunction with RYGB (n = 34). The RYGB group lost more weight and had greater improvement in HbA1c. Fasting glucose was lower after RYGB than after LS/IMM, although the glucose area under the curve decreased comparably for both groups. Insulin sensitivity increased in both groups. Insulin secretion was unchanged after LS/IMM but decreased after RYGB, except for a rapid increase during the first 30 min after meal ingestion. Glucagon-like peptide 1 (GLP-1) was substantially increased after RYGB, while gastric inhibitory polypeptide and glucagon decreased. Lower HbA1c was most strongly correlated with the percentage of weight loss for both groups. At baseline, a greater C-peptide index and 90-min postprandial C-peptide level were predictive of lower HbA1c at 1 year after RYGB. β-Cell glucose sensitivity, which improved only after RYGB, and improved disposition index were associated with lower HbA1c in both groups, independent of weight loss. Weight loss and preserved β-cell function both predominantly determine the greatest glycemic benefit after RYGB., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Bioresorbable medical devices once implanted into the body are "invisible" to imaging techniques such as X-ray/fluoroscopy and magnetic resonance imagining (MRI). Prior attempts to produce radiopaque polymers have limited success due to their inability to generate homogeneous mixtures of polymer and contrast agent without subsequent alterations in polymer structure. Here we investigate a novel approach in which a MRI contrast medium, gadodiamide, can be used as a polymerization initiator in poly(propylene fumarate) (PPF) synthesis to achieve a radiopaque and MRI-visible polymer poly(gadodiamide fumaric acid) (PGFA). With this method polymer structure, thermal properties, and rheological behavior are conserved with no prior manipulation to monomer units necessary. This unique polymer in combination with poly(lactic- co -glycolic acid) (PLGA) can be formulated into MRI-visible nanoparticles with drug delivery potential. This novel polymer in both liquid and nanoparticle form enables new possibilities in medical device and drug delivery design.

An imine-based approach was developed to prepare Janus gold nanoparticles (Janus AuNPs) having amine functionality on one patch of the surface and a polyethylene glycol unit on the other. This unique technique features covalent bonding as the force to immobilize AuNPs on the template, enabling direct modification of AuNPs in both water and organic solvents. Colloidal clusters were then obtained via electrostatic assembly of these Janus AuNPs with citrate stabilized AuNPs or AgNPs.

A series of N-heterocyclic quinoxaline derivatives was successfully synthesized and applied as hole transport layers in quantum dot light-emitting diodes (QLEDs). By inducing sp(2) N-atoms into the quinoxaline backbone, the electron affinity of the obtained material was enhanced, and its optical properties and bandgap became tunable. Quinoxaline based N-heteroacenes show a narrow bandgap, high thermal stability, and aligned film morphology. The resulting N-heteroacene polymer based QLED exhibits superior performance to poly(9-vinylcarbazole) based QLED. This study presents a strategy towards the design of novel N-rich molecules for the fabrication of QLEDs with improved performance.