In the event of a nuclear detonation, a considerable number of projected casualties will suffer from combined radiation exposure and burn and/or wound injury. Countermeasure assessment in the setting of radiation exposure combined with dermal injury is hampered by a lack of animal models in which the effects of interventions have been characterized. To address this need, we used two separate models to characterize wound closure. The first was an open wound model in mice to study the effect of wound size in combination with whole-body 6 Gy irradiation on the rate of wound closure, animal weight and survival (morbidity). In this model the addition of interventions, wound closure, subcutaneous vehicle injection, topical antiseptic and topical antibiotics were studied to measure their effect on healing and survival. The second was a rat closed wound model to study the biomechanical properties of a healed wound at 10 days postirradiation (irradiated with 6 or 7.5 Gy). In addition, complete blood counts were performed and wound pathology by staining with hematoxylin and eosin, trichrome, CD68 and Ki67. In the mouse open wound model, we found that wound size and morbidity were positively correlated, while wound size and survival were negatively correlated. Regardless of the wound size, the addition of radiation exposure delayed the healing of the wound by approximately 5-6 days. The addition of interventions caused, at a minimum, a 30% increase in survival and improved mean survival by ?9 days. In the rat closed wound model we found that radiation exposure significantly decreased all wound biomechanical measurements as well as white blood cell, platelet and red blood cell counts at 10 days post wounding. Also, pathological changes showed a loss of dermal structure, thickening of dermis, loss of collagen/epithelial hyperplasia and an increased density of macrophages. In conclusion, we have characterized the effect of a changing wound size in combination with radiation exposure. We also demonstrated that the most effective interventions mitigated insensible fluid loss, which could help to define the most appropriate requirements of a successful countermeasure.
In this study, unique luminescent gels have been obtained from two components between amino acid functionalized perylene derivatives and 4,4'-bipyridyl units via hierarchical self-assembly. The luminescent gels have been investigated by means of ultraviolet spectra (UV), fluorescence spectra, Scanning Electron Microscopy (SEM) and Laser Scanning Confocal Microscopy (LSCM), which illustrate the strong fluorescence intensity of the gels. In order to further reveal the self-assembly driving forces, the two-dimensional (2D) self-assembly behaviours have been studied by scanning tunneling microscopy (STM) on a highly oriented pyrolytic graphite (HOPG) substrate at the solid-liquid interface, which indicates that the driving forces are attributed to the intermolecular hydrogen bonding and ?-? stacking interactions. According to the interaction mode, these organogelators are found to rapidly transform from gels to solutions by adding triethylamine.
The purpose of this study was to develop and characterize a novel photo-cross-linkable chitosan-lactide-fibrinogen (CLF) hydrogel and evaluate the efficacy of bone morphogenetic protein-2 (BMP-2) containing a CLF hydrogel for osteogenesis in vitro and in vivo. We synthesized the CLF hydrogels and characterized their chemical structure, degradation rate, compressive modulus and in vitro BMP-2 release kinetics. We evaluated bioactivities of the BMP-2 containing CLF hydrogels (0, 50, 100 and 500ngml(-1)) in vitro using W-20-17 preosteoblast mouse bone marrow stromal cells and C2C12 mouse myoblast cells. The effect of BMP-2 containing CLF gels (0, 0.5, 1, 2 and 5?g) on bone formation was evaluated using rat critical size segmental bone defects for 4weeks. Fourier transform infrared spectroscopy spectra and scanning electron microscopy images showed chemical and structural changes by the addition of fibrinogen into the chitosan-lactide copolymer. The incorporation of fibrinogen molecules significantly increased the compressive modulus of the hydrogels. The in vitro BMP-2 release study showed initial burst releases from the CLF hydrogels followed by sustained releases, regardless of the concentration of the BMP-2 over 4weeks. Cells in all groups were viable in the presence of the hydrogels regardless of BMP-2 doses, indicating non-cytotoxicity of hydrogels. Alkaline phosphate activity and mineralization of cells exhibited dose dependence on BMP-2 containing CLF hydrogels. Radiography, microcomputed tomography and histology confirmed that the BMP-2 containing CLF hydrogels prompted neo-osteogenesis and accelerated healing of the defects in a dose-dependent manner. Thus the CLF hydrogel is a promising delivery system of growth factors for bone regeneration.
Lung cancer is one of the world's highest morbidity and mortality disease in malignant tumors currently. Squamous-cell lung cancer (SQCLC) is one of the most prevalent subtypes of lung cancer worldwide, after surgery, radiotherapy, chemotherapy and other comprehensive treatment, its 5-year survival rate is still below 15%. The current molecular targeted therapy plays an important role in the treatment of SQCLC, an urgent need to be more in-depth study. SQCLC molecular targeted therapy mainly epidermal growth factor receptor (EGFR), phosphoin-3-kinase catalytic alpha polypeptide (PIK3CA), fibroblast growth factor receptor 1 (FGFR1), discoidin domain receptor 2 (DDR2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), BRAF, MET, insulin-like growth factor 1 receptor (IGF-1R) and other as the target of the drug, some targeted drugs are being developed, and some targeted drugs have entered clinical trials. In recent years, with studies molecular targeted therapy in SQCLC, analysis of the development and trgeted therapy achieved substantial progress in improving the survival rate of SQCLC, and other research to improve the quality of life, make is possible to individualized targeted therapy of SQCLC.
The shape control of platinum nanocrystals is significant to the enhancement of their catalytic performance in terms of activity and selectivity. However, it still remains a major challenge to prepare Pt nanocrystals with tunable shape and clean surface in an eco-friendly way. This article develops a facile and green strategy to prepare well tuned platinum nanocrystals employing poly(diallyldimethylammonium chloride) (PDDA) as the capping agent, reductant, and stabilizer simultaneously in a facile hydrothermal process. It is identified that the variation of PDDA concentration is crucial to control the growth of crystalline facets, leading to the formation of cubic, truncated cubic, and octahedral Pt nanocrystals with sizes tunable from ca. 17 nm to ca. 50 nm. The resultant Pt nanocrystals exhibit excellent electrocatalytic activity and stability toward the oxygen reduction reaction (ORR) in acidic media compared with those of commercial Pt black and the state-of-the-art Pt/C catalyst. It is proposed that the preferential Pt surface and the decoration of PDDA, which modulates the electronic structures and electrooxidation of Pt nanocrystals, synergistically contribute to the enhanced catalytic performance.
Vapor condensation on solid surfaces plays a crucial role across a wide range of industrial applications. Recent advances of nanotechnology have made possible the manipulation of the condensation process through the control of surface structures. In this work, we study vapor condensation on hydrophobic surfaces patterned with microscale pillars. The critical nuclei, the activation barriers, and the minimum energy paths are computed using the climbing string method. The effects of pillar height, interpillar spacing, the level of supersaturation, and the intrinsic wettability of the solid surface on the nucleation process are investigated. Two nucleation scenarios are obtained from the computation. In the case of high pillar, narrow interpillar spacing, low supersaturation, and/or low surface wettability, the critical nucleus prefers the suspended Cassie state; otherwise, it prefers the impaled Wenzel state. A comparison of the nucleation barrier with that on a flat surface of the same material reveals that vapor condensation is inhibited by the microstructures in the former case, while enhanced in the latter case. The critical values of the pillar height, the interpillar spacing, and the supersaturation at which the critical nucleus changes from the Cassie state to the Wenzel state are identified from the phase diagram of the critical nucleus. It is found that the dependence of the critical interpillar spacing on the supersaturation follows closely the curve of the critical radii in a homogeneous nucleation. The relaxation dynamics of the condensate after the critical nucleus is formed is computed by solving the steepest descent equation. It is observed that when the pillar is low and/or the interpillar spacing is wide, a condensate initially in the Cassie state may evolve into the Wenzel state during the relaxation.
Lithium compound deposition on mesocarbon microbead (MCMB) anode after long-term cycling was studied in LiCoO2/MCMB battery. Lithium compound deposition did not generate on the activated MCMB anode, but it generated unevenly on the long-term cycled anode. Gray deposition composed of dendrites and particles was formed on the lower surface of the MCMB layer first, then on the upper surface. The deposition and MCMB layer peeled off from the current collector, and a bump was formed in the cycled anode. The exfoliation and thick deposition increased the ohmic resistance, film resistance, and charge transfer resistance of the cell and decreased the capacity significantly. Metallic lithium did not exist in either the upper or the lower deposition layer according to the results of X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), the discharge curve, and anode potential. The outer region of both the lower and the upper deposition layers consisted of Li2CO3, LiOH, ROCO2Li, and ROLi. The inner region of the etched lower deposition layer mainly consisted of Li2O, LiF, and Li2CO3, and that of the etched upper deposition layer mainly consisted of Li2CO3, ROCO2Li, ROLi, and LiF. Solid electrolyte interphase (SEI) film hindering the intercalation of lithium ions into carbon layers and LiCoO2 cathode providing lithium source for the deposition were the two reasons leading to the formation of lithium compound deposition during long-term cycles. Because SEI film on the lower surface of MCMB layer was thicker than that on the upper surface, lithium compound deposition generated on the lower surface first.
Astroviruses infect humans and many animal species and cause gastroenteritis. To extensively understand the distribution and genetic diversity of astrovirus in small mammals, we tested 968 anal swabs from 39 animal species, most of which were bats and rodents. We detected diverse astroviruses in 10 bat species, including known bat astroviruses and a large number of novel viruses. Meanwhile, novel groups of astroviruses were identified in three wild rodent species and a remarkably high genetic diversity of astrovirus was revealed in Eothenomys cachinus. We detected astroviruses in captive-bred porcupines and a nearly full-length genome sequence was determined for one strain. Phylogenetic analysis of the complete ORF2 sequence suggested that this strain may share a common ancestor with porcine astrovirus type 2. Moreover, to our knowledge, this study reports the first discovery of astroviruses in shrews and pikas. Our results provide new insights for understanding these small mammals as natural reservoirs of astroviruses.
The traditional Chinese theory of acupuncture emphasizes that the intensity of acupuncture must reach a threshold to generate de qi (a specific and compound sensation during the acupuncture), which is necessary to achieve the best therapeutic effect. However, the notion that de qi must be achieved for maximum benefit has not been confirmed by modern scientific evidence. This study aims to compare the efficacy of acupuncture with either strong (intended to elicit de qi) or weak stimulation among patients with allergic rhinitis.
One of the main challenges for clinical implementation of small diameter vascular grafts (SDVGs) is their limited hemocompatibility. Important design specifications for such grafts include features that minimize the long-term risks of restenosis, fouling, and thrombus formation. In our lab, we have developed elastomeric hollow fiber membranes (HFMs), using a phase inversion method, as candidates for SDVGs. Here, we present our results for in vitro hemocompatibility testing of our HFM under flow and static conditions. Our results showed that the polymer-based HFMs do not damage the integrity of human red blood cells (RBCs) as shown by their low hemolytic extent (less than 2%). When analyzed for blood cell lysis using lactate dehydrogenase (LDH) activity as an indicator, no significant differences were observed between blood exposed to our HFMs and uncoagulated blood. Analysis of protein adsorption showed a low concentration of proteins deposited on the surfaces of HFM after 24?h. Platelet adhesion profiles using human platelet-rich plasma (PRP) showed that a low level of platelets adhered to the HFMs after 24?h, indicating minimal thrombotic potential. Under the majority of conditions, no significant differences were observed between medical-grade polymers and our HFMs. Eventual optimization of hemocompatible elastomeric HFM vessel grafts could lead to improved tissue vascularization as well as vascularized, tissue-engineered scaffolds for organ repair.
Treatment of large bone defects using synthetic scaffolds remain a challenge mainly due to insufficient vascularization. This study is to engineer a vascularized bone graft by integrating a vascularized biomimetic cell-sheet-engineered periosteum (CSEP) and a biodegradable macroporous beta-tricalcium phosphate (?-TCP) scaffold. We first cultured human mesenchymal stem cells (hMSCs) to form cell sheet and human umbilical vascular endothelial cells (HUVECs) were then seeded on the undifferentiated hMSCs sheet to form vascularized cell sheet for mimicking the fibrous layer of native periosteum. A mineralized hMSCs sheet was cultured to mimic the cambium layer of native periosteum. This mineralized hMSCs sheet was first wrapped onto a cylindrical ?-TCP scaffold followed by wrapping the vascularized HUVEC/hMSC sheet, thus generating a biomimetic CSEP on the ?-TCP scaffold. A nonperiosteum structural cell sheets-covered ?-TCP and plain ?-TCP were used as controls. In vitro studies indicate that the undifferentiated hMSCs sheet facilitated HUVECs to form rich capillary-like networks. In vivo studies indicate that the biomimetic CSEP enhanced angiogenesis and functional anastomosis between the in vitro preformed human capillary networks and the mouse host vasculature. MicroCT analysis and osteocalcin staining show that the biomimetic CSEP/?-TCP graft formed more bone matrix compared to the other groups. These results suggest that the CSEP that mimics the cellular components and spatial configuration of periosteum plays a critical role in vascularization and osteogenesis. Our studies suggest that a biomimetic periosteum-covered ?-TCP graft is a promising approach for bone regeneration.
Breast cancer has become one of the most common malignant tumors among females over the past several years. Breast carcinogenesis is a continuous process, which is featured by the normal epithelium progressing to premalignant lesions and then to invasive breast cancer (IBC). Targeting premalignant lesions is an effective strategy to prevent breast cancer. The establishment of animal models is critical to study the mechanisms of breast carcinogenesis, which will facilitate research on breast cancer prevention and drug behaviors. In this study, we established a feasible chemically-induced rat model of premalignant breast cancer.
Vascularization remains a critical challenge in tissue engineering. The development of vascular networks within densely populated and metabolically functional tissues facilitate transport of nutrients and removal of waste products, thus preserving cellular viability over a long period of time. Despite tremendous progress in fabricating complex tissue constructs in the past few years, approaches for controlled vascularization within hydrogel based engineered tissue constructs have remained limited. Here, we report a three dimensional (3D) micromolding technique utilizing bioprinted agarose template fibers to fabricate microchannel networks with various architectural features within photocrosslinkable hydrogel constructs. Using the proposed approach, we were able to successfully embed functional and perfusable microchannels inside methacrylated gelatin (GelMA), star poly(ethylene glycol-co-lactide) acrylate (SPELA), poly(ethylene glycol) dimethacrylate (PEGDMA) and poly(ethylene glycol) diacrylate (PEGDA) hydrogels at different concentrations. In particular, GelMA hydrogels were used as a model to demonstrate the functionality of the fabricated vascular networks in improving mass transport, cellular viability and differentiation within the cell-laden tissue constructs. In addition, successful formation of endothelial monolayers within the fabricated channels was confirmed. Overall, our proposed strategy represents an effective technique for vascularization of hydrogel constructs with useful applications in tissue engineering and organs on a chip.
Blood-feeding insects, as vectors of disease for humans and livestock alike, have garnered significant interest, but our understanding of their early evolution is hindered by the scarcity of available material and the difficulty in distinguishing early hematophages from non-blood-feeding relatives. Here, we report a new family of true bugs including two new genera and species from the Early Cretaceous Yixian Formation in Northeastern China. By utilizing geochemical methods for determining their diets and combining morphological and taphonomic data, we demonstrate that these new species represent the earliest evidence of blood feeding among true bugs, extending the geological record of such lineages by approximately 30 million years. Remarkably, one of the bugs appears to have perished immediately following a blood meal, which may have been from coexisting mammals, birds, or avian-related dinosaurs. These records expand the phylogenetic and ecological diversity of blood-feeding insects in the Early Cretaceous, enriching our knowledge of paleoecological associations in these ancient environments.
Escitalopram appears to be a superior antidepressant to racemic citalopram. It has been hypothesized that binding of R-citalopram to the serotonin transporter (SERT) antagonizes escitalopram binding to and inhibition of the SERT, thereby curtailing the elevation of extracellular 5-hydroxytryptamine (5-HTExt), and hence antidepressant efficacy. Further, it has been suggested that a putative allosteric binding site is important for binding of escitalopram to the primary, orthosteric, site, and for R-citalopram's inhibition hereof.
Vascularization of three-dimensional large synthetic grafts for tissue regeneration remains a significant challenge. Here we demonstrate an electrochemical approach, named the cell electrochemical detachment (CED) technique, to form an integral endothelium and use it to prevascularize a collagen-?-tricalcium phosphate (?-TCP) graft. The CED technique electrochemically detached an integral endothelium from a gold-coated glass rod to a collagen-infiltrated, channeled, macroporous ?-TCP scaffold, forming an endothelium-lined microchannel containing graft upon removal of the rod. The in vitro results from static and perfusion culture show that the endothelium robustly emanated microvascular sprouting and prevascularized the entire collagen/?-TCP integrated graft. The in vivo subcutaneous implantation studies show that the prevascularized collagen/?-TCP grafts established blood flow originating from the endothelium-lined microchannel within a week, and the blood flow covered more areas in the graft over time. In addition, many blood vessels invaded the prevascularized collagen/?-TCP graft and the in vitro preformed microvascular networks anastomosed with the host vasculature, while collagen alone without the support of rigid ceramic scaffold showed less blood vessel invasion and anastomosis. These results suggest a promising strategy for effectively vascularizing large tissue-engineered grafts by integrating multiple hydrogel-based CED-engineered endothelium-lined microchannels into a rigid channeled macroporous scaffold.
Tuberculosis (TB) remains to be an enormous global health problem. The inconsistent protection efficacy of Bacille Calmette-Guérin (BCG) calls for new vaccines for TB. One choice to improve the efficacy of BCG vaccine is recombinant BCG (rBCG). Experimental evidences have revealed that Ag85B, ESAT-6 and Rv3620c are important immunodominant antigens of Mycobacterium tuberculosis. In this study, we have constructed a novel rBCG expressing fusion protein Ag85B-ESAT6-Rv3620c and evaluated the immunogenicity of this rBCG in C57BL/6 mice. Results show that there is a strong TB-specific CD4(+) and CD8(+) T lymphocytes proliferation in mice immunized with this rBCG vaccine. A single dose immunization of rBCG could induce a significantly strong Th1 immune response characterized by an increasing ratio of antigen-specific IgG2b/IgG1 as well as a high expression level of Th1 cytokines such as IFN-?, TNF-? and IL-2. This conclusion was confirmed by a decreased secretion of Th2 cytokine IL-10. Moreover, this rBCG induced a strong humoral response in mice with an increasing antigen-specific IgG titer. Therefore, we concluded that this rBCG could significantly increase both Th1 type cellular immune response and antigen-specific humoral response compared with BCG. The above observations demonstrated that rBCG::Ag85B-ESAT6-Rv3620c is a potential candidate vaccine against M. tuberculosis for further study.
Echovirus 33 (E33) has been infrequently detected and is less frequently associated with clinical diseases when compared with other types of enteroviruses (EVs) in China. An outbreak of E33 was identified in four schools in Hunan Province, China, in June 2013. For laboratory diagnosis, throat swabs and/or serum specimens were collected from 27 patients. E33 was isolated in cell culture and typed by molecular methods. Complete VP1 gene sequences were determined and analyzed. Specific E33 antibody was measured by virus neutralization testing. From June 3-20, 108 suspected cases were reported, and 19 were confirmed to be associated with E33 by laboratory testing, with seven virologically confirmed and 12 serologically confirmed cases. The suspected cases were in children aged 3-16 years (mean, 11 years), most of whom (94%, 102/108) were ?6 years old. The majority of cases (98%, 106/108) presented as influenza-like illness (ILI), and two were clinically diagnosed as viral meningitis. Older children aged ?12 years had a higher hospitalization rate (21%) than younger children (4%). A BLAST query of GenBank with the Hunan E33 strain VP1 gene sequence gave a close match to an E33 isolate from Pakistan, based on a partial VP1 gene sequence. Phylogenetic analyses of the complete E33 VP1 gene sequences from our study revealed an independent cluster with nucleotide sequences that diverge from E33 from other countries by >12%. Due to limited E33 VP1 gene sequence data in GenBank and passive EV surveillance in China and most other parts of the world (excepting hand, foot, and mouth disease surveillance in Asia), the approximate origin of Hunan E33 could not be determined.
We provide here a comparative genome analysis of 31 strains within the genus Paenibacillus including 11 new genomic sequences of N2-fixing strains. The heterogeneity of the 31 genomes (15 N2-fixing and 16 non-N2-fixing Paenibacillus strains) was reflected in the large size of the shell genome, which makes up approximately 65.2% of the genes in pan genome. Large numbers of transposable elements might be related to the heterogeneity. We discovered that a minimal and compact nif cluster comprising nine genes nifB, nifH, nifD, nifK, nifE, nifN, nifX, hesA and nifV encoding Mo-nitrogenase is conserved in the 15 N2-fixing strains. The nif cluster is under control of a ?(70)-depedent promoter and possesses a GlnR/TnrA-binding site in the promoter. Suf system encoding [Fe-S] cluster is highly conserved in N2-fixing and non-N2-fixing strains. Furthermore, we demonstrate that the nif cluster enabled Escherichia coli JM109 to fix nitrogen. Phylogeny of the concatenated NifHDK sequences indicates that Paenibacillus and Frankia are sister groups. Phylogeny of the concatenated 275 single-copy core genes suggests that the ancestral Paenibacillus did not fix nitrogen. The N2-fixing Paenibacillus strains were generated by acquiring the nif cluster via horizontal gene transfer (HGT) from a source related to Frankia. During the history of evolution, the nif cluster was lost, producing some non-N2-fixing strains, and vnf encoding V-nitrogenase or anf encoding Fe-nitrogenase was acquired, causing further diversification of some strains. In addition, some N2-fixing strains have additional nif and nif-like genes which may result from gene duplications. The evolution of nitrogen fixation in Paenibacillus involves a mix of gain, loss, HGT and duplication of nif/anf/vnf genes. This study not only reveals the organization and distribution of nitrogen fixation genes in Paenibacillus, but also provides insight into the complex evolutionary history of nitrogen fixation.
This study was designed to explore the effectiveness and safety of the combination of bronchoscopic interventions and percutaneous modalities in treating thyroid cancers with airway invasion. A total of 13 patients, 5 men and 8 women, were retrospectively included into this study. All patients received bronchoscope treatment. Rigid bronchoscope was used to explore, ventilate, and dilate airway obstruction for temporary control in nine patients. Tumors were scavenged by CO2 cryosurgery combined with argon plasma coagulation (APC) in 11 patients. Four covered Z-type recoverable tracheal stents were selected for four patients. All patients had good airway control and palliative respiratory symptoms following treatments. Ten patients were further treated with CT guided (125)I seed permanent implantation, and one patient was treated with argon-helium cryoablation. The median local control was 22 months (10-55 months). The follow-up period ranged from 10 to 55 months (median 22 months). Three patients (23.1 %) died of local recurrence, one of whom was due to airway obstruction and poor physical condition, two of whom with bleeding from relapsed tumor. One patient (7.7 %) died of acute myocardial infraction. Nine patients (69.2 %) were still alive according to the last follow-up. (125)I seed implantation and argon-helium cryoablation did not induce apparent complications. The combination of bronchoscopic interventions and percutaneous modalities might be a feasible and safe method for thyroid cancer patients with airway invasion.
The induced membrane has been widely used in the treatment of large bone defects but continues to be limited by a relatively lengthy healing process and a requisite two stage surgical procedure. Here we report the development and characterization of a synthetic biomimetic induced membrane (BIM) consisting of an inner highly pre-vascularized cell sheet and an outer osteogenic layer using cell sheet engineering. The pre-vascularized inner layer was formed by seeding human umbilical vein endothelial cells (HUVECs) on a cell sheet comprised of a layer of undifferentiated human bone marrow-derived mesenchymal stem cells (hMSCs). The outer osteogenic layer was formed by inducing osteogenic differentiation of hMSCs. In vitro results indicated that the undifferentiated hMSC cell sheet facilitated the alignment of HUVECs and significantly promoted the formation of vascular-like networks. Furthermore, seeded HUVECs rearranged the extracellular matrix produced by hMSC sheet. After subcutaneous implantation, the composite constructs showed rapid vascularization and anastomosis with the host vascular system, forming functional blood vessels in vivo. Osteogenic potential of the BIM was evidenced by immunohistochemistry staining of osteocalcin, tartrate-resistant acid phosphatase (TRAP) staining, and alizarin red staining. In summary, the synthetic BIM showed rapid vascularization, significant anastomoses, and osteogenic potential in vivo. This synthetic BIM has the potential for treatment of large bone defects in the absence of infection.
Visual fixation plays a key role in the differentiation between vegetative state/unresponsive wakefulness (VS/UWS) syndrome and minimally conscious state (MCS). However, the use of different stimuli changes the frequency of visual fixation occured in patients, thereby possibly affecting the accuracy of the diagnosis. In order to establish a standardized assessment of visual fixation in patients in disorders of consciousness (DOC), we compared the frequency of visual fixation elicited by mirror,a ball and a light.
Recently, a class of multifunctional Ti alloys called GUM metals attracts tremendous attentions for their superior mechanical behaviors (high strength, high ductility and superelasticity) and novel physical properties (Invar effect, Elinvar effect and low modulus). The Invar and Elinvar effects are known to originate from structural or magnetic transitions, but none of these transitions were found in the GUM metals. This challenges our fundamental understanding of their physical properties. In this study, we show that the typical GUM metal Ti-23Nb-0.7Ta-2Zr-1.2O (at%) alloy undergoes a strain glass transition, where martensitic nano-domains are frozen gradually over a broad temperature range by random point defects. These nano-domains develop strong texture after cold rolling, which causes the lattice elongation in the rolling direction associated with the transition upon cooling and leads to its Invar effect. Moreover, its Elinvar effect and low modulus can also be explained by the nano-domain structure of strain glass.
Here we report the development and characterization of novel photo-crosslinkable chitosan-lactide (Ch-LA) hydrogels for bone tissue engineering. We synthesized the hydrogels based on Ch, LA, and methacrylic anhydride (MA), and examined their chemical structures, degradation rates, compressive moduli, and protein release kinetics. We also evaluated the cytotoxicity of the hydrogels and delivery efficacy of bone morphogenetic protein-2 (BMP-2) on osteoblast differentiation and mineralization using W-20-17 preosteoblast mouse bone marrow stromal cells and C2C12 mouse myoblast cells. NMR and FTIR revealed that the hydrogels were formed via amidation and esterification between Ch and LA, and methacrylation for photo-crosslinkable networks. Addition of a hydrophobic LA moiety to a hydrophilic Ch chain increased swellability, softness, and degradation rate of the photo-crosslinkable Ch-LA hydrogels. Changes in Ch/LA ratio and UV exposure time significantly affected compressive modulus and protein release kinetics. The photo-crosslinkable Ch-LA hydrogels were not cytotoxic regardless of the composition and UV crosslinking time. Higher alkaline phosphatase activities of both W-20-17 and C2C12 cells were observed in the less-crosslinked hydrogels at day 5. Mineralization was enhanced by sustained BMP-2 release from the hydrogels, but was cell type dependent. This photo-crosslinkable Ch-LA hydrogel is a promising carrier for growth factors.
A 7.0-magnitude earthquake hit Lushan County in China's Sichuan province on April 20, 2013, resulting in 196 deaths and 11,470 injured. This study was designed to analyze the characteristics of the injuries and the treatment of the seismic victims.
We investigated avian influenza infections in wild birds, poultry, and humans at Eastern Dongting Lake, China. We analyzed 6,621 environmental samples, including fresh fecal and water samples, from wild birds and domestic ducks that were collected from the Eastern Dongting Lake area from November 2011 to April 2012. We also conducted two cross-sectional serological studies in November 2011 and April 2012, with 1,050 serum samples collected from people exposed to wild birds and/or domestic ducks. Environmental samples were tested for the presence of avian influenza virus (AIV) using quantitative PCR assays and virus isolation techniques. Hemagglutination inhibition assays were used to detect antibodies against AIV H5N1, and microneutralization assays were used to confirm these results. Among the environmental samples from wild birds and domestic ducks, AIV prevalence was 5.19 and 5.32%, respectively. We isolated 39 and 5 AIVs from the fecal samples of wild birds and domestic ducks, respectively. Our analysis indicated 12 subtypes of AIV were present, suggesting that wild birds in the Eastern Dongting Lake area carried a diverse array of AIVs with low pathogenicity. We were unable to detect any antibodies against AIV H5N1 in humans, suggesting that human infection with H5N1 was rare in this region.
Motivated by the challenges in assessing physician-level cancer screening performance and the negative impact of misclassification, we propose a method (using mammography as an example) that enables confident assertion of adequate or inadequate performance or alternatively recognizes when more data is required.
Au nanobipyramids (NBPs) are important nanostructures which attract much attention due to their unique structure, optical, and catalytic properties. The controlled synthesis of Au NBPs and corresponding mechanistic study are highly desirable for both fundamental research and practical applications. Herein, we demonstrate a strategy that large sized Au decahedra with well-defined shape act as seeds for growing NBPs. Furthermore, through using different sized decahedra seeds with edge from 25 to 49 nm, various sized NBPs can be easily prepared (longitudinal length from 110 to 210 nm; transverse length from 36 to 70 nm). Our study provides hard evidence for the growth of NBPs that they surely stem from the overgrowth on penta-twinned decahedra. Because these used large size seeds have well-defined shape and structure, the growth of the NBPs can be easily determined. Results show that the formation of NBPs is primarily determined by the molar ratio of Au(3+) and Au seeds (MRAA). MRAA less than 4 only causes size enhancement and no significant shape change. In cases of MRAA higher than 4 and lower than 8, quasi-nanorods are produced. When MRAA range from 8 to 10, NBPs form and the yield is higher than 90%. The effect of reaction time and temperature also are vital to the growth of NBPs. These prepared NBPs are found to exhibit excellent surface enhanced Raman scattering (SERS) performance because of many present hotspots, edges, steps, and tips on their surfaces.
NQO1 (NAD(P)H: quinone oxidoreductase, also known as DT-diaphorase) plays a prominent role in maintaining cellular homeostasis. NQO1 is abnormally elevated in many solid cancer types, including those of the adrenal gland, breast, colon, lung, ovary, and thyroid. However, little is known about the status of NQO1 in gastric adenocarcinoma (GAC). To investigate the clinicopathological significance of NQO1 expression in GAC, and thus evaluate its role as a potential prognostic marker, 203 cases of primary GAC, 31 of gastric dysplasia, and 53 of adjacent non-tumor tissues were selected for immunohistochemical staining of NQO1 protein. Correlations between NQO1 overexpression and clinicopathological characteristics were evaluated by ?(2) test and Fishers exact test, while survival rates were calculated by the Kaplan-Meier method. The relationship between prognostic factors and patient survival was analyzed by the Cox proportional hazards model. Through these analyses it was found that the strongly positive rate of NQO1 protein was significantly higher than that of gastric dysplasia and adjacent non-tumor tissues. Analysis by qRT-PCR also confirmed that NQO1 mRNA levels were increased in GAC compared with that detected in either adjacent non-tumor tissues or normal gastric mucosa. Additionally, the NQO1 expression rate was positively correlated with tumor size, serosal invasion, tumor stage, and both disease-free survival and 5-year survival rates. Further analysis showed that although NQO1 was not an independent predictor of GAC, elevated expression of NQO1 could predict lower disease-free survival and 5-year survival times in late-stage patients. In conclusion, NQO1 plays an important role in the progression of GAC, and might be a potential, but not an independent, poor prognostic biomarker and therapeutic target of GAC.
An H12N8 subtype avian influenza virus (AIV) was isolated from a wild bird in China in 2011. It is the first report of isolation of the H12N8 subtype AIV in Asia. Phylogenetic analysis results suggested it is a reassortant, and all eight gene segments belong to the Eurasian gene pool.
The K(+)-induced switching of valinomycin has been studied using a molecular template formed by an aromatic oligoamide macrocycle at the liquid/solid interface by scanning tunneling microscopy (STM). Individual valinomycin and its K(+) complex can be identified and resolved in the molecular template, and the high-resolution STM images of valinomycin and its K(+) complex show triangle-like and cyclic structural characteristics, respectively.
A twin T-DNA system is a convenient strategy for creating selectable marker-free transgenic plants. The standard transformation plasmid, pCAMBIA 1300, was modified into a binary vector consisting of two separate T-DNAs, one of which contained the hygromycin phosphotransferase (hpt) marker gene. Using this binary vector, we constructed two vectors that expressed inverted-repeat (IR) structures targeting the rice stripe virus (RSV) coat protein (CP) gene and the special-disease protein (SP) gene. Transgenic rice lines were obtained via Agrobacterium-mediated transformation. Seven independent clones harbouring both the hpt marker gene and the target genes (RSV CP or SP) were obtained in the primary transformants of pDTRSVCP and pDTRSVSP, respectively. The segregation frequencies of the target gene and the marker gene in the T1 plants were 8.72 percent for pDTRSVCP and 12.33 percent for pDTRSVSP. Two of the pDTRSVCP lines and three pDTRSVSP lines harbouring the homozygous target gene, but not the hpt gene, were strongly resistant to RSV. A molecular analysis of the resistant transgenic plants confirmed the stable integration and expression of the target genes. The resistant transgenic plants displayed lower levels of the transgene transcripts and specific small interfering RNAs, suggesting that RNAi induced the viral resistance.
In inflammatory sites, high molecular weight hyaluronan fragments are degraded into lower molecular weight hyaluronan fragments (LMW-HA) to regulate immune responses. However, the function of LMW-HA in PTC progression remains to be elucidated. In this study, we found that receptor of LMW-HA, TLR4, was aberrantly overexpressed in PTC tissues and cell line W3. Exposure of W3 cells to LMW-HA promoted cell proliferation and migration via TLR4. Knockdown of TLR4 has provided evidence that TLR4 is essential for LMW-HA-induced CXCR7 expression, which is responsible for LMW-HA-induced proliferation and migration of W3 cells. In tumor-bearing adult nude mice, stimulation of LMW-HA on W3 cells promotes CXCR7 expression in tumor masses (P = 0.002) and tumor growth (P < 0.001). To further confirm our findings, we investigated the clinicopathologic significance of TLR4 and CXCR7 expression using immumohistochemistry in 135 human PTC tissues and 56 normal thyroid tissue samples. Higher rates of TLR4 (53%) and CXCR7 (24%) expression were found in PTC tissues than in normal tissues. Expression of TLR4 or CXCR7 is associated with tumor size and lymph node metastasis. Therefore, LMW-HA may contribute to the development of PTC via TLR4/CXCR7 pathway, which may be a novel target for PTC immunomodulatory therapy.
Schistosomiasis is one of the most burdensome of the neglected tropical diseases. Praziquantel is a recommended drug for treatment against all forms of schistosomiasis. To investigate the interaction between praziquantel and Schistosoma japonicum cercariae, two praziquantel derivatives (PZQ-2 and PZQ-3) and one praziquantel fluorescent derivative (PZQ-5) have been synthesized and characterized using nuclear magnetic resonance spectroscopy (NMR) and MS spectra. The cytotoxicity of PZQ-2, PZQ-3 and PZQ-5 was measured by performing the methyl thiazolyl tetrazolium (MTT) assay. The cell viability for them shows that the three compounds exhibit low cytotoxicity to HeLa cells. Cell imaging experiments demonstrate that PZQ-5 is biocompatible and cell-permeable, which indicates that PZQ-5 is suitable for studying their interaction. Confocal fluorescence microscopy revealed that PZQ-5 is mainly located at the cercarial tegument, which leads to the death of cercariae with the increase in time.
Colorectal cancer is the second leading cause of death from cancer in the United States. To facilitate the efficiency of colorectal cancer screening, there is a need to stratify risk for colorectal cancer among the 90% of US residents who are considered "average risk." In this article, we investigate such risk stratification rules for advanced colorectal neoplasia (colorectal cancer and advanced, precancerous polyps). We use a recently completed large cohort study of subjects who underwent a first screening colonoscopy. Logistic regression models have been used in the literature to estimate the risk of advanced colorectal neoplasia based on quantifiable risk factors. However, logistic regression may be prone to overfitting and instability in variable selection. Since most of the risk factors in our study have several categories, it was tempting to collapse these categories into fewer risk groups. We propose a penalized logistic regression method that automatically and simultaneously selects variables, groups categories, and estimates their coefficients by penalizing the $$L1$$-norm of both the coefficients and their differences. Hence, it encourages sparsity in the categories, i.e. grouping of the categories, and sparsity in the variables, i.e. variable selection. We apply the penalized logistic regression method to our data. The important variables are selected, with close categories simultaneously grouped, by penalized regression models with and without the interactions terms. The models are validated with 10-fold cross-validation. The receiver operating characteristic curves of the penalized regression models dominate the receiver operating characteristic curve of naive logistic regressions, indicating a superior discriminative performance.
While transforming growth factor ? (TGF?) signaling plays a critical role in chondrocyte metabolism, the TGF? signaling pathways and target genes involved in cartilage homeostasis and the development of osteoarthritis (OA) remain unclear. Using an in vitro cell culture method and an in vivo mouse genetic approach, we undertook this study to investigate TGF? signaling in chondrocytes and to determine whether Mmp13 and Adamts5 are critical downstream target genes of TGF? signaling.
The development of engineered nucleases is the fruit of a new technological approach developed in the last two decades which has led to significant benefits on genome engineering, particularly on gene therapy. These applications enable efficient and specific genetic modifications via the induction of a double-strand break (DSB) in a specific genomic target sequence, followed by the homology-directed repair (HDR) or non-homologous end joining (NHEJ) pathways. In addition to the application on gene modification in cells and intact organisms, a number of recent papers have reported that this gene editing technology can be applied effectively to human diseases. With the promising data obtained using engineered endonucleases in gene therapy, it appears reasonable to expect that more diseases could be treated and even be cured in this new era of individualized medicine. This paper first brief introduces the development of engineered nucleases with a special emphasis on zinc-finger nucleases (ZFNs) and transcription activator-like effector (TALE) nucleases (TALENs), and then takes CCR5-based gene therapy as an example to discuss the therapeutic applications of engineered nucleases.
The tumor-node-metastasis (TNM) staging system has been the anchor of cancer diagnosis, treatment, and prognosis for many years. For meaningful clinical use, an orderly, progressive condensation of the T and N categories into an overall staging system needs to be defined, usually with respect to a time-to-event outcome. This can be considered as a cutpoint selection problem for a censored response partitioned with respect to two ordered categorical covariates and their interaction. The aim is to select the best grouping of the TN categories. A novel bootstrap cutpoint/model selection method is proposed for this task by maximizing bootstrap estimates of the chosen statistical criteria. The criteria are based on prognostic ability including a landmark measure of the explained variation, the area under the receiver operating characteristic (ROC) curve, and a concordance probability generalized from Harrells c-index. We illustrate the utility of our method by applying it to the staging of colorectal cancer.
The structure and dynamics properties of water molecules at the interface of the charged monolayer-protected Au nanoparticle (MPAN) have been investigated in detail by using classical molecular dynamics simulation. The simulation results demonstrated clearly that a well-defined hydration layer is formed at the interface of MPAN and a stable "ion wall" consisting of terminal NH3 (+) groups and Cl(-) counterions exists at the outmost region of self-assembled monolayer (SAM) where the translational and rotational motions of water molecules slow considerably down compared to those in the bulk owing to the presence of SAM and ion wall. Furthermore, we found that the translational motions of interfacial water molecules display a subdiffusive behavior while their rotational motions exhibit a nonexponential feature. The unique behavior of interfacial water molecules around the MPAN can be attributed to the interfacial hydrogen bond (HB) dynamics. By comparison, the lifetime of NH3 (+)-Cl(-) HBs was found to be the longest, favoring the stability of ion wall. Meanwhile, the lifetime of H2O-H2O HBs shows an obvious increase when the water molecules approach the Au core, suggesting the enhanced H2O-H2O HBs around the charged MPAN, which is contrary to the weaken H2O-H2O HBs around the neutral MPAN. Moreover, the HB lifetimes between water molecules and the ion wall (i.e., the Cl(-)-H2O and NH3 (+)-H2O HBs) are much longer than that of interfacial H2O-H2O HBs, which leads to the increasing rotational relaxation time and residence time of water molecules surrounding the ion wall. In addition, the corresponding binding energies for different HB types obtained from the precise density functional theory are in excellent accordance with above simulation results. The detailed HB dynamics studied in this work provides insights into the unique behavior of water molecules at the interface of charged self-assemblies of nanoparticles as well as proteins.
The co-digestion of fruit & vegetable waste (FVW) and food waste (FW) was performed at various organic loading ratios (OLRs) in single-phase and two-phase system, respectively. The results showed that the ethanol-type fermentation dominated in both digestion processes when OLR was at low levels (<2.0 g(VS) L(-1) d(-1)). The propionic acid was rapidly accumulated as OLR was increased to higher levels (>2.0 g(VS) L(-1) d(-1)), which could cause unstable anaerobic digestion. Single-phase digestion was better than two-phase digestion in term of 4.1% increase in CH4 production at lower OLRs (<2.0 g(VS) L(-1) d(-1)). However, at higher level of OLR (?2.0 g(VS) L(-1) d(-1)), two-phase digestion achieved higher CH4 production of 0.351-0.455 L(g VS)(-1) d(-1), which were 7.0-15.8% more than that of single-phase. Additionally, two-phase digestion presented more stable operation, and higher OLR treatment capacity. Furthermore, comparison of these two systems with bioenergy recovery revealed that two-phase system overall presented higher bioenergy yield than single-phase.
As a lignocellulose-based substrate for anaerobic digestion, rice straw is characterized by low density, high water absorbability, and poor fluidity. Its mixing performances in digestion are completely different from traditional substrates such as animal manures. Computational fluid dynamics (CFD) simulation was employed to investigate mixing performances and determine suitable stirring parameters for efficient biogas production from rice straw. The results from CFD simulation were applied in the anaerobic digestion tests to further investigate their reliability. The results indicated that the mixing performances could be improved by triple impellers with pitched blade, and complete mixing was easily achieved at the stirring rate of 80 rpm, as compared to 20-60 rpm. However, mixing could not be significantly improved when the stirring rate was further increased from 80 to 160 rpm. The simulation results agreed well with the experimental results. The determined mixing parameters could achieve the highest biogas yield of 370 mL (g TS)(-1) (729 mL (g TS(digested))(-1)) and 431 mL (g TS)(-1) (632 mL (g TS(digested))(-1)) with the shortest technical digestion time (T 80) of 46 days. The results obtained in this work could provide useful guides for the design and operation of biogas plants using rice straw as substrates.
A facile method is reported to prepare Maillard reaction products (MRPs) from chitosan and xylan in co-solvent ionic liquid. UV absorbance and fluorescence changes were regarded as indicators of the occurrence of Maillard reaction. FT-IR, NMR, XRD and TG were used to investigate the structure of chitosan-xylan conjugate. The results revealed that when chitosan reacted with xylan in ionic liquid, the hydrogen bonds in chitosan were destroyed, the facts resulted in the formation of chitosan-xylan MRPs. Moreover, when the mass ratio of chitosan to xylan was 1:1, the Maillard reaction proceeded easily. In addition, relatively high antioxidant property was also noted for the chitosan-xylan conjugate with mass ratio 1:1. So the obtained chitosan-xylan MRP is a promising antioxidant agent for food industry.
This study evaluated whether the combination of biodegradable ?-tricalcium phosphate (?-TCP) scaffolds with recombinant human bone morphogenetic protein-2 (rhBMP-2) or platelet-rich plasma (PRP) could accelerate bone formation and increase bone height using a rabbit non-through cranial bone defect model. Four non-through cylindrical bone defects with a diameter of 8-mm were surgically created on the cranium of rabbits. ?-TCP scaffolds in the presence and absence of impregnated rhBMP-2 or PRP were placed into the defects. At 8 and 16 weeks after implantation, samples were dissected and fixed for analysis by microcomputed tomography and histology. Only defects with rhBMP-2 impregnated ?-TCP scaffolds showed significantly enhanced bone formation compared to non-impregnated ?-TCP scaffolds (P < 0.05). Although new bone was higher than adjacent bone at 8 weeks after implantation, vertical bone augmentation was not observed at 16 weeks after implantation, probably due to scaffold resorption occurring concurrently with new bone formation.
Sepsis is a leading cause of morbidity and mortality in critically ill patients. OMICS and systems pharmacology approaches offer the promise of new therapeutic candidates for the treatment of patients with sepsis. Qin-Re-Jie-Du (QRJD) and Liang-Xue-Huo-Xue (LXHX) are two traditional Chinese herbal medicine (CHM) formulas with putative effects in sepsis treatment. The present study aimed to assess their efficacy in an experimental model of sepsis in rats (cecal ligation and punctures) and investigate their mechanism of action using a 1H-NMR metabolomics approach. Rats were randomly divided into four groups (i.e., model group, sham control group, and two CHM treatment groups). Water extracts of QRJD and LXHX were orally administered to the two CHM treatment groups at a dose of 24?g/kg of body weight, once daily for 3 consecutive days. The same volume of 0.9% saline solution was orally administered to the model and sham surgery groups. Plasma samples were collected and measured using 600?MHz 1H-NMR spectroscopy. As a result, 18 potential metabolite biomarkers involved in multiple metabolic pathways, including increased energy metabolism, fat mobilization, and disrupted amino acid metabolism, were identified in septic rats. The principal component analysis (PCA) and partial least squares discriminant (PLS-DA) plots of the metabolic state correlated well with the mortality and clinical biochemistry results. An analysis of potential biomarkers verified the holistic effects of the two CHM formulas. The Cori cycle was positively regulated in the QRJD-treated formulas treatment group but also inhibited in the LXHX-treated group, which demonstrates the different efficacies of these solutions in septic rats.
Various methods exist in the literature for achieving marginal balance for baseline stratification variables in sequential clinical trials. One major limitation with balancing on the margins of the stratification variables is that there is an efficiency loss when the primary analysis is stratified. To preserve the efficiency of a stratified analysis one recently proposed approach balances on the crossing of the stratification variables included in the analysis, which achieves conditional balance for the variables. A hybrid approach to achieving both marginal and conditional balances in sequential clinical trials is proposed, which is applicable to both continuous and categorical stratification variables. Numerical results based on extensive simulation studies and a real dataset show that the proposed approach outperforms the existing ones and is particularly useful when both additive and stratified models are planned for a trial.
Ti-Nb-based Gum Metals exhibit extraordinary superelasticity with ultralow elastic modulus, superior strength and ductility, and a peculiar dislocation-free deformation behavior, most of which challenge existing theories of crystal strength. Additionally, this kind of alloys actually displays even more anomalous mechanical properties, such as the non-linear superelastic behavior, accompanied by a pronounced tension-to-compression asymmetry, and large ductility with a low Poissons ratio. Two main contradictory arguments exist concerning the deformation mechanisms of those alloys, i.e., formation of reversible nanodisturbance and reversible martensitic transformation. Herein we used the in-situ synchrotron high-energy X-ray scattering technique to reveal the novel intrinsic physical origin of all anomalous mechanical properties of the Ti-24Nb-4Zr-8Sn-0.10O alloy, a typical gum-like metal. Our experiments provide direct evidence on two different kinds of interesting, stress-induced, reversible nanoscale martensitic transitions, i.e., the austenitic regions with B2 structure transform to ?? martensite and those with BCC structure transform to ? martensite.
Over 200 published studies of more than 30 plant species have reported a role for miRNAs in regulating responses to abiotic stresses. However, data from these individual reports has not been collected into a single database. The lack of a curated database of stress-related miRNAs limits research in this field, and thus a cohesive database system should necessarily be constructed for data deposit and further application.
Osteogenetic microenvironment is a complex constitution in which extracellular matrix (ECM) molecules, stem cells and growth factors each interact to direct the coordinate regulation of bone tissue development. Importantly, angiogenesis improvement and revascularization are critical for osteogenesis during bone tissue regeneration processes. In this study, we developed a three-dimensional (3D) multi-scale system model to study cell response to growth factors released from a 3D biodegradable porous calcium phosphate (CaP) scaffold. Our model reconstructed the 3D bone regeneration system and examined the effects of pore size and porosity on bone formation and angiogenesis. The results suggested that scaffold porosity played a more dominant role in affecting bone formation and angiogenesis compared with pore size, while the pore size could be controlled to tailor the growth factor release rate and release fraction. Furthermore, a combination of gradient VEGF with BMP2 and Wnt released from the multi-layer scaffold promoted angiogenesis and bone formation more readily than single growth factors. These results demonstrated that the developed model can be potentially applied to predict vascularized bone regeneration with specific scaffold and growth factors.
Interleukin-23 receptor (IL23R) can interact with IL-23 and, thus, is involved in the T-helper 17 (Th17) cell-mediated inflammatory process as well as tumorigenesis. Recently, a functional single nucleotide polymorphism (SNP) rs10889677 has been identified in the 3-untranslated region of IL-23R. It has been showed that the rs10889677AC SNP could increase the binding affinity of microRNA let-7f and downregulate IL-23R expression. Several case-control studies have examined the association between this SNP and genetic susceptibility of multiple solid tumors. However, the conclusions are conflicting. Therefore, we conducted this meta-analysis to systematically study the role of this functional IL-23R SNP in development of multiple solid tumors. There are a total of 5 studies are eligible (6731 cases and 7296 healthy controls). Either fixed-effect model or random-effect model was used to calculate pooled odds ratios (ORs) and the 95% confidence interval (95% CI). Significant association between this functional rs10889677 genetic variant and risk of multiple solid tumors were observed (CC genotype vs. AA genotype: OR = 0.59, 95% CI = 0.53-0.66, P < 0.001). These findings demonstrated that the IL-23R rs10889677 genetic variant might play an important part during malignant transformation of multiple solid tumors.
The survivin polymorphisms have been shown to confer genetic susceptibility to various tumors, but the results are inconsistent. In order to accomplish a more precise estimation of the relationship, a meta-analysis was performed.
Cytomegalovirus retinitis is a common AIDS-associated illness, leading to blindness in up to 30% of patients. This study was to investigate the prevalence and clinical management of the cytomegalovirus retinitis associated with AIDS in a large municipality of China.
Molecular hydrogen (H(2)) is an efficient antioxidant that can selectively reduce hydroxyl radicals and inhibit oxidative stress-induced injuries. We investigated the protective effects and mechanism of hydrogen-rich saline in a glutamate-induced retinal injury model. Retinal excitotoxicity was induced in healthy guinea pigs by injecting glutamate into the vitreous cavity. After 30 min, hydrogen-rich saline was injected into the vitreous cavity, the peritoneal cavity or both. Seven days later, the retinal stress response was evaluated by examining the stress biomarkers, inducible nitric-oxide synthase (iNOS) and glucose-regulated protein 78 (GRP78). The impaired glutamate uptake was assessed by the expression of the excitatory amino acid transporter 1(EAAT-1). The retinal histopathological changes were investigated, focusing on the thicknesses of the entire retina and its inner layer, the number of cells in the retinal ganglion cell layer (GCL) and the ultrastructure of the retinal ganglion cells (RGCs) and glial cells. Compared with the glutamate-induced injury group, the hydrogen-rich saline treatment reduced the loss of cells in the GCL and thinning of the retina and attenuated cellular morphological damage. These improvements were greatest in animals that received H(2) injections into both the vitreous and the peritoneal cavities. The hydrogen-rich saline also inhibited the expression of glial fibrillary acidic protein (GFAP) in Müller cells, CD11b in microglia, and iNOS and GRP78 in glial cells. Moreover, the hydrogen-rich saline increased the expression of EAAT-1. In conclusion, the administration of hydrogen-rich saline through the intravitreal or/and intraperitoneal routes could reduce the retinal excitotoxic injury and promote retinal recovery. This result likely occurs by inhibiting the activation of glial cells, decreasing the production of the iNOS and GRP78 and promoting glutamate clearance.
Porous ?-tricalcium phosphate (?-TCP) has been used for bone repair and replacement in clinics due to its excellent biocompatibility, osteoconductivity, and biodegradability. However, the application of ?-TCP has been limited by its brittleness. Here, we demonstrated that an interconnected porous ?-TCP scaffold infiltrated with a thin layer of poly (lactic-co-glycolic acid) (PLGA) polymer showed improved mechanical performance compared to an uncoated ?-TCP scaffold while retaining its excellent interconnectivity and biocompatibility. The infiltration of PLGA significantly increased the compressive strength of ?-TCP scaffolds from 2.90 MPa to 4.19 MPa, bending strength from 1.46 MPa to 2.41 MPa, and toughness from 0.17 MPa to 1.44 MPa, while retaining an interconnected porous structure with a porosity of 80.65%. These remarkable improvements in the mechanical properties of PLGA-coated ?-TCP scaffolds are due to the combination of the systematic coating of struts, interpenetrating structural characteristics, and crack bridging. The in vitro biological evaluation demonstrated that rat bone marrow stromal cells (rBMSCs) adhered well, proliferated, and expressed alkaline phosphatase (ALP) activity on both the PLGA-coated ?-TCP and the ?-TCP. These results suggest a new strategy for fabricating interconnected macroporous scaffolds with significantly enhanced mechanical strength for potential load-bearing bone tissue regeneration.
As an aetiological agent of bacterial sepsis and wound infections, Vibrio vulnificus is unique among the Vibrionacea. Its continued environmental persistence and transmission are bolstered by its ability to colonize shellfish and form biofilms on various marine biotic surfaces. We previously identified a polysaccharide locus, brp, which contributes to the survival phenotypes of biofilm formation, rugose colony formation and stress resistance. Here, we describe a second polysaccharide locus, rbd (regulation of biofilm development), which also enhanced biofilm formation when expressed. Despite this functional overlap, the development of stress resistance and rugosity could be uniquely attributed to brp expression, whereas rbd expression augmented aggregate formation. Simultaneous expression of both loci led to the formation of a dramatic pellicle and maximum biofilm formation. Unlike the brp locus, transcription of the rbd locus was regulated not by c-di-GMP, but by a response regulator (RbdG) that was encoded within the locus. We propose that the ability to regulate the expression of polysaccharides with overlapping and unique characteristics in response to different environmental cues enables V. vulnificus to fine tune its biofilm lifestyle to the prevailing environmental conditions and maximally benefit from the characteristics associated with each polysaccharide.
Treating airway fistulas, including esophagorespiratory fistulas (ERFs), bronchopleural fistulas (BPFs), and tracheomediastinal fistulas (TMFs), is difficult. The aim of this study is to evaluate the safety and clinical efficacy of metallic covered Z-type stents (CZTS) for the treatment of airway fistulas through bronchoscopy or fluroscopy.
Obstructive atelectasis is frequently accompanied by pulmonary infection and hypoxia. The key to treating this condition is by directly reopening the obstructive airway. The aim of the present study is to explore the safety and efficacy of interventional bronchoscopy for the treatment of malignant obstructive atelectasis.
Monte Carlo (MC) methods are the gold standard for modeling photon and electron transport in a heterogeneous medium; however, their computational cost prohibits their routine use in the clinic. Cloud computing, wherein computing resources are allocated on-demand from a third party, is a new approach for high performance computing and is implemented to perform ultra-fast MC calculation in radiation therapy. We deployed the EGS5 MC package in a commercial cloud environment. Launched from a single local computer with Internet access, a Python script allocates a remote virtual cluster. A handshaking protocol designates master and worker nodes. The EGS5 binaries and the simulation data are initially loaded onto the master node. The simulation is then distributed among independent worker nodes via the message passing interface, and the results aggregated on the local computer for display and data analysis. The described approach is evaluated for pencil beams and broad beams of high-energy electrons and photons. The output of cloud-based MC simulation is identical to that produced by single-threaded implementation. For 1 million electrons, a simulation that takes 2.58 h on a local computer can be executed in 3.3 min on the cloud with 100 nodes, a 47× speed-up. Simulation time scales inversely with the number of parallel nodes. The parallelization overhead is also negligible for large simulations. Cloud computing represents one of the most important recent advances in supercomputing technology and provides a promising platform for substantially improved MC simulation. In addition to the significant speed up, cloud computing builds a layer of abstraction for high performance parallel computing, which may change the way dose calculations are performed and radiation treatment plans are completed.
Novel circular ssDNA genomes have recently been detected in animals and in the environment using metagenomic and high-throughput sequencing approaches. In this study, five full-length circular ssDNA genomes were recovered from bat faecal samples using inverse PCR with sequences designed based on circovirus-related sequences obtained from Solexa sequencing data derived from a random amplification method. These five sequences shared a similar genomic organization to circovirus or the recently proposed cyclovirus of the family Circoviridae. The newly obtained circovirus/cyclovirus-like genomes ranged from 1741 to 2177 bp, and each consisted of two major ORFs, ORF1 and ORF2, encoding putative replicase (Rep) and capsid (Cap) proteins, respectively. The potential stem-loop region was predicted in all five genomes, and three of them had the typical conserved nonanucleotide motif of cycloviruses. A set of primers targeting the conserved Rep region was designed and used to detect the prevalence of circovirus/cyclovirus sequences in individual bats. Among 199 samples tested, 47 were positive (23.6%) for the circovirus genome and two (1.0%) were positive for the cyclovirus genome. In total, 48 partial Rep sequences plus the five full-length genomes were obtained in this study. Detailed analysis indicated that these sequences are distantly related to known circovirus/cyclovirus genomes and may represent 22 novel species that belong to the family Circoviridae.
As an etiological agent of bacterial sepsis and wound infections, Vibrio vulnificus is unique among the Vibrionaceae. The most intensely studied of its virulence factors is the capsular polysaccharide (CPS). Over 100 CPS types have been identified, yet little is known about the genetic mechanisms that drive such diversity. Chitin, the second-most-abundant polysaccharide in nature, is known to induce competence in Vibrio species. Here, we show that the frequency of chitin-induced transformation in V. vulnificus varies by strain and that (GlcNAc)(2) is the shortest chitin-derived polymer capable of inducing competence. Transformation frequencies (TFs) increased 8-fold when mixed-culture biofilms were exposed to a strain-specific lytic phage, suggesting that the lysis of dead cells during lytic infection increased the amount of extracellular DNA within the biofilm that was available for transfer. Furthermore, we show that V. vulnificus can undergo chitin-dependent carbotype conversion following the uptake and recombination of complete cps loci from exogenous genomic DNA (gDNA). The acquisition of a partial locus was also demonstrated when internal regions of homology between the endogenous and exogenous loci existed. This suggested that the same mechanism governing the transfer of complete cps loci also contributed to their evolution by generating novel combinations of CPS biosynthesis genes. Since no evidence that cps loci were preferentially acquired during natural transformation (random transposon-tagged DNA was readily taken up in chitin transformation assays) exists, the phenomenon of chitin-induced transformation likely plays an important but general role in the evolution of this genetically promiscuous genus.
A major challenge in tissue engineering is to reproduce the native 3D microvascular architecture fundamental for in vivo functions. Current approaches still lack a network of perfusable vessels with native 3D structural organization. Here we present a new method combining self-assembled monolayer (SAM)-based cell transfer and gelatin methacrylate hydrogel photopatterning techniques for microengineering vascular structures. Human umbilical vein cell (HUVEC) transfer from oligopeptide SAM-coated surfaces to the hydrogel revealed two SAM desorption mechanisms: photoinduced and electrochemically triggered. The former, occurs concomitantly to hydrogel photocrosslinking, and resulted in efficient (>97%) monolayer transfer. The latter, prompted by additional potential application, preserved cell morphology and maintained high transfer efficiency of VE-cadherin positive monolayers over longer culture periods. This approach was also applied to transfer HUVECs to 3D geometrically defined vascular-like structures in hydrogels, which were then maintained in perfusion culture for 15 days. As a step toward more complex constructs, a cell-laden hydrogel layer was photopatterned around the endothelialized channel to mimic the vascular smooth muscle structure of distal arterioles. This study shows that the coupling of the SAM-based cell transfer and hydrogel photocrosslinking could potentially open up new avenues in engineering more complex, vascularized tissue constructs for regenerative medicine and tissue engineering applications.
Vascular endothelial growth factor C (VEGF-C), a member of the VEGF family, has been reported to promote angiogenesis and tumor cell growth. In this study, we analyzed inhibitory action of a VEGF-C antisense oligoxydeonucleotide (ASODN) on a lung carcinoma cell line A-549 and its invasive ability in vitro.
We investigated the effect of sustained release of bone morphogenetic protein-2 (BMP-2) from an injectable chitosan gel on osteoblastic differentiation in vitro. We first characterized the release profile of BMP-2 from the gels, and then examined the cellular responses of preosteoblast mouse stromal cells (W-20-17) and human embryonic palatal mesenchymal (HEPM) cells to BMP-2. The release profiles of different concentrations of BMP-2 exhibited sustained releases (41% for 2 ng/mL and 48% for 20 ng/mL, respectively) from the chitosan gels over a three-week period. Both cell types cultured in the chitosan gels were viable and significantly proliferated for 3 days (p < 0.05). Chitosan gels loaded with BMP-2 enhanced ALP activity of W-20-17 by 3.6-fold, and increased calcium mineral deposition of HEPM by 2.8-fold at 14 days of incubation, compared to control groups initially containing the same amount of BMP-2. In addition, schitosan gels loaded with BMP-2 exhibited significantly greater osteocalcin synthesis of W-20-17 at seven days, and of HEPM at both 7 and 14 days compared with the control groups (p<0.05). This study suggests that the enhanced effects of BMP-2 released from chitosan gels on cell differentiation and mineralization are species and cell type dependent.
A new genus with a new species of Saldidae, Brevrimatus pulchalifergen. et sp. n., is described and illustrated. The fossil specimen was found from the Early Cretaceous Yixian Formation of Duolun County, Inner Mongolia, China. Phylogenetic analyses within Saldidae were performed, and the results indicate Brevrimatus pulchalifergen. et sp. n. should be assigned to the subfamily Chiloxanthinae.
Single-layer anastomosis has been used extensively for all gastrointestinal tracts around the world. Until now, most surgeons take for granted that submucous layers need careful hemostasis either by electric coagulation or ligation for the prevention of anastomotic stoma bleeding. We experienced hemostasis in the submucosa layer by adequate strength of anastomosis rather than electric coagulation for gastrointestinal tracts. In the present study the safety and benefit of this novel anastomotic technique was evaluated. From 1994 to 2006, 527 gastrointestinal anastomosis were performed using the improved anastomotic technique, and 281 anastomosis (control group) were completed with the commonly adopted technique. The improved anastomotic technique could decreased the incidence of leaks (p = 0.024), and the procedure time required for anastomosis in comparison to control group (p = 0.0002). The incidence of abscesses (p = 0.51) and bleeding (p = 1.00) of the improved anastomotic technique were no significantly different between the groups. The novel technique, single-layer anastomosis without hemostasis in the submucosa layer by electric coagulation or ligation, is suitable for all gastrointestinal anastomosises and it should be popularized.
Treatment of critical airway stenoses remains a formidable challenge to surgeons and anesthesiologists. Suffocate is a leading cause of death if the patients with airway diseases were not treated properly. The purpose of this study is to explore the feasibility, safety and efficiency using video-assisted rigid bronchoscopes (VARB) in the treatment of central airway stenoses.
Related JoVE Video
Journal of Visualized Experiments
What is Visualize?
JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.
How does it work?
We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.
Video X seems to be unrelated to Abstract Y...
In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.