Speckle image reconstruction, in which the speckle transfer function (STF) is modeled as annular distribution according to the angular dependence of adaptive optics (AO) compensation and the individual STF in each annulus is obtained by the corresponding Fried parameter calculated from the traditional spectral ratio method, is used to restore the solar images corrected by AO system in this paper. The reconstructions of the solar images acquired by a 37-element AO system validate this method and the image quality is improved evidently. Moreover, we found the photometric accuracy of the reconstruction is field dependent due to the influence of AO correction. With the increase of angular separation of the object from the AO lockpoint, the relative improvement becomes approximately more and more effective and tends to identical in the regions far away the central field of view. The simulation results show this phenomenon is mainly due to the disparity of the calculated STF from the real AO STF with the angular dependence.
A novel metal-organic framework [Cd3(TPT)2(DMF)2]·(H2O)0.5 () has been solvothermally synthesized using a new rigid unsymmetrical tricarboxylate ligand p-terphenyl-3,4'',5-tricarboxylic acid (H3TPT). Single-crystal X-ray diffraction analysis reveals that possesses a three-dimensional (3D) framework with an alb-4,8-C2/c topology constructed by the combination of Cd-carboxylate chains and TPT linkers. The ?-electron rich ligand H3TPT enables to have an excellent luminescent property. The micrometer-sized compound dispersed in ethanol exhibits high efficiency detection for picric acid (PA). The high efficiency, stability and recyclability of make it a potential chemosensor for nitroaromatic explosives.
In the present study, an extracellular copper-zinc superoxide dismutase (ecCuZnSOD) gene and a mitochondrial manganese superoxide dismutase (mtMnSOD) gene were cloned from hemocytes of red claw crayfish, Cherax quadricarinatus. The open reading frame (ORF) of ecCuZnSOD is 498 bp and encodes a 166 amino acids (aa) protein, whereas the ORF of mtMnSOD is 654 bp and encodes a 218 aa protein. The amino acid sequences of C. quadricarinatus ecCuZnSOD and mtMnSOD showed high similarities with those of ecCuZnSODs and mtMnSODs of other crustaceans, respectively. Both ecCuZnSOD and mtMnSOD of C. quadricarinatus were highly expressed in hepatopancreas, hemocytes, intestine, and gill; low transcript levels were seen in other tissues (heart, muscle, and nerve). The immune responses of ecCuZnSOD and mtMnSOD were studied following inoculation with Spiroplasma eriocheiris and Aeromonas hydrophila. After S. eriocheiris or A. hydrophila challenge, mRNA transcription of ecCuZnSOD and mtMnSOD in hemocytes and gill was upregulated. mRNA transcription of ecCuZnSOD in the hepatopancreas was also upregulated after S. eriocheiris or A. hydrophila inoculation. mtMnSOD in hepatopancreas was upregulated after A. hydrophila inoculation, whereas this was down-regulated after S. eriocheiris challenge. After S. eriocheiris and A. hydrophila challenge, total SOD activity and CuZnSOD activity both increased compared to control group. The results showed that these SODs from C. quadricarinatus likely play an important role in protecting some tissues from reactive oxygen intermediates produced during challenge from S. eriocheiris and A. hydrophila.
We demonstrate an all-fiber transverse self-accelerating Bessel-like beam generator and its optical trapping application. The theoretical and experimental studies have been provided to verify this beam properties. We produce the Bessel-like beam by splicing the single-mode fiber and multimode fiber with a defined offset and then modulating the output light beam phase by fabricating a small hemispherical-lens fiber tip; therefore, the phase-modulated Bessel-like beam generates the properties of transverse self-accelerating. The transverse acceleration of the the Bessel-like beam generated here is ?10-4???m-1, which is almost 100 times larger than that of the beam generated in the free-space optical circuit based on the lens. The experimental and simulated results have good consistencies. The realization of the microparticle transverse acceleration transporting with this Bessel-like beam provides a new method for microparticles to be transported in a bending trajectory. This all-fiber transverse self-accelerating Bessel-like beam generator structure is simple, with high integration and small size, and constitutes a new development for high-precision biological cell experiments and manipulations.
Body plethysmography is a typical method to measure functional residual capacity (FRC) and airway resistance (Raw). The aim of the study was to test the feasibility of measuring lung function with the body plethysmography in young children with acute lower respiratory tract infection (ALRI) by evaluating changes and prognosis of lung function for infants with ALRI with or without wheezing via body plethysmograph.
Chondrosarcoma is characterized by secretion of a cartilage-like matrix, with high proliferation ability and metastatic potential. Previous studies have shown that parathyroid hormone-related protein (PTHrP) has a close relationship with various tumor types. The objectives of this study were to research the function played by PTHrP in human chondrosarcoma, especially targeting cell proliferation and invasion, and to search for the potential interaction between PTHrP and primary cilia in tumorigenesis. Surgical resection tissues and the human chondrosarcoma cell line SW1353 were used in the scientific research. Cells were stimulated with an optimum concentration of recombinant PTH (1-84), and siRNA was used to interfere with internal PTHrP. Cell proliferation and invasion assays were applied, including MTS-8 cell proliferation assay, Western blot, RT-PCR, Transwell invasion assay, and immunohistochemistry and immunofluorescence assays. A high level of PTHrP expression was found in human chondrosarcoma tissues, and recombinant PTH exhibited positive promotion in tumor cell proliferation and invasion. In the meantime, PTHrP could inhibit the assembly of primary cilia and regulate downstream gene expression. These findings indicate that PTHrP can regulate tumor cell proliferation and invasion ability, possibly through suppression of primary cilia assembly. Thus, restricting PTHrP over-expression is a feasible potential therapeutic method for chondrosarcoma.
Fatty Acid Desaturase (FADS) genes and their variants have been associated with multiple metabolic phenotypes including liver enzymes and hepatic fat accumulation but the detailed mechanism remains unclear. We aimed to delineate the role of FADSs in modulating lipid composition in human liver. We performed a targeted lipidomic analysis of a variety of phospholipids, sphingolipids and ceramides among 154 human liver tissue samples. The associations between previously Genome-wide Association Studies (GWAS)-identified six FADS single nucleotide polymorphisms (SNPs) and these lipid levels as well as total hepatic fat content (HFC) were tested. The potential function of these SNPs in regulating transcription of 3 FADS genes (FADS1, FADS2 and FADS3) in the locus was also investigated. We found that while these SNPs were in high linkage disequilibrium (r(2) >0.8), the rare alleles of these SNPs were consistently and significantly associated with the accumulation of multiple very-long-chain fatty acids (VLCFAs), with C47H85O13P (C36:4), a phosphatidylinositol (PI) and C43H80O8PN (C38:3), a phosphatidylethanolamine (PE) reached the Bonferroni corrected significance (p<3×10(-4) ). Meanwhile, these SNPs were significantly associated with increased ratios between the more saturated and relatively less saturated forms of VLCFAs, especially between PEs, PIs and phosphatidylcholines (PCs) (p?3.5×10(-6) ). These alleles were also associated with increased total HFC (p<0.05). Further analyses revealed that these alleles were associated with decreased hepatic expression of FADS1 (p=0.0018 for rs174556), but not FADS2 or FADS3 (p>0.05). Conclusion: Our findings revealed critical insight into the mechanism underlying FADS1 and its polymorphisms in modulating hepatic lipid deposition by altering gene transcription and controlling lipid composition in human livers. (Hepatology 2014;).
IFN-?, an essential cytokine in the viral cell-mediated immune response, has been associated with the pathogenesis of respiratory syncytial virus (RSV) bronchiolitis and to the severity of the infection. The aim of this study was to investigate whether IFN-? CA microsatellite (rs3138557) polymorphism was associated with susceptibility to RSV in Chinese Han children and with the severity of the infection.
The propagation dynamics of all-fiber plasmonic double parallel and orthogonal Airy beams are experimentally demonstrated. Two slits and groove arrays were fabricated by focused ion beam (FIB) milling on the gold coated end facet of an optical fiber to generate two Airy beams simultaneously. Sub-wavelength self-focusing of double parallel Airy beams in free space is experimentally verified. Effects of geometrical parameters on the intensity profiles of the focal spot are analyzed in detail. The characteristics at the junction of the two main lobes can be adjusted by controlling the initial phase difference of the two Airy beams. The propagation of two orthogonal Airy beams is also experimentally investigated. Multi-Airy beams are of importance to realize all-fiber optical trapping, fiber integrated devices, and laser shaping.
The residual aberrations of adaptive optics (AO) images can be removed by the speckle reconstruction method. To achieve accurate photometry, the knowledge of the speckle transfer function (STF) is necessary. In this Letter, a new method is proposed to evaluate the STF for speckle image reconstruction based on the partial correction AO. The STF is divided into two sections: the low-frequency section and the high-frequency section, and two different generalized Fried parameters for the partial wavefront compensation are used to calculate the STF values of those two different sections. This method is tested with the different seeing conditions and the various correction modes. The results show that the combined STFs have satisfactory agreement with the simulated AO STFs and give more accurate results than the STFs obtained from the traditional spectral ratio method. Further discussions show that the method is more reliable when the AO is operated in low-order correction mode because the approximation of the STF and the two generalized Fried parameters have better accuracy when the pupil diameter is much larger than those generalized Fried parameters.
Unlike annuals, all perennial plants undergo seasonal transitions during ontogeny. As an adaptive response to seasonal changes in climate, the seasonal pattern of growth is likely to be under genetic control, although its underlying genetic basis remains unknown. Here, we develop a computational model that can map specific quantitative trait loci (QTLs) responsible for seasonal transitions of growth in perennials. The model is founded on functional mapping, a statistical framework to map developmental dynamics, which is reformed to integrate a seasonally adjusted growth function. The new model is equipped with a capacity to characterize the genetic effects of QTLs on seasonal alternation at different ages and then to better elucidate the genetic architecture of development. The model is implemented with a series of testing procedures, including (i) how a QTL controls an overall ontogenetic growth curve, (ii) how the QTL determines seasonal trajectories of growth within years and (iii) how it determines the dynamic nature of age-specific season response. The model was validated through computer simulation. The extension of season adjustment to other types of biological curves is statistically straightforward, facilitating a wider variety of genetic studies into ontogenetic growth and development in perennial plants.
Abstract Intervertebral discs comprise the largest avascular cartilaginous organ in the body, and its nutrient condition can be impaired by degeneration, aging and even metabolic disease. The unique microenvironment brings special stresses to various disc cell types, including nucleus pulposus cells, notochordal cells, annulus fibrosus cells and endplate chondrocytes. These cells experience nutrient starvation, acidic stress, hypoxic stress, hyperglycemic stress, osmotic stress and mechanical stress. Understanding the detailed responses and complex adaptive mechanisms of disc cells to various stresses might provide some clues to guide therapy for disc degeneration. By reviewing the published literatures describing disc cells under different hostile microenvironments, we conclude that these cells exhibit different responses to microenvironmental stresses with different mechanisms. Moreover, the interaction and combination of these stresses create a complex environment that synergistically increase or decrease influences on disc cells, compared with the effects of a single stress. Interestingly, most of these stresses activate autophagy, a self-protective mechanism by which dysfunctional protein and organelles are degraded. It is becoming clear that autophagy facilitates the cellular adaptation to stresses and might play a central role in regulating the adaptation of disc cells under stress. Therefore, autophagy modulation might be a potential therapeutic method to treat disc degeneration.
Cell?based therapy is a potential alternative to liver transplantation. The goal of the present study was to examine the in vivo and in vitro hepatic differentiation potential of adipose tissue?derived mesenchymal stem cells (AT?MSCs) and to explore its therapeutic use. AT?MSCs were isolated and cultured with hepatic differentiation medium. Bioactivity assays were used to study the properties of AT?MSCs. The morphology of differentiated AT?MSCs in serum?free hepatic differentiation medium changed into polygonal epithelial cells, while the morphology of AT?MSCs in a similar medium containing 2% fetal bovine serum remained unchanged. The differentiated cells cultured without serum showed hepatocyte?like cell morphology and hepatocyte?specific markers, including albumin (ALB) and ??fetoprotein. The bioactivity assays revealed that hepatocyte?like cells could take up low?density lipoprotein (LDL) and store glycogen. Furthermore, trichostatin A (TSA) enhanced ALB production and LDL uptake by the hepatocyte?like cells, analogous to the functions of human liver cells. ALB was detected in the livers of the CCl4?injured mice one month post?transplantation. This suggested that transplantation of the human AT?MSCs could relieve the impairment of acute CCl4?injured livers in nude mice. This therefore implied that adipose tissue was a source of multipotent stem cells which had the potential to differentiate into mature, transplantable hepatocyte?like cells in vivo and in vitro. In addition, the present study determined that TSA was essential to promoting differentiation of human MSC towards functional hepatocyte?like cells. The relief of liver injury following treatment with AT?MSCs suggested their potential as a novel therapeutic method for liver disorders or injury.
Clostridium perfringens is an important pathogen causing sudden death syndrome, necrotic enteritis, and gas gangrene in ruminants, especially some deer species. Père David's deer (Elaphurus davidianus) is one of the world's rare species and is an endangered and protected species in China. Some Père David's deer in the Chinese Shishou Père David's Deer Preserve died due to C. perfringens infection. We investigated the toxin types and C. perfringens enterotoxin-positive (cpe(+)) strains of isolated C. perfringens in Père David's deer in China. We collected 155 fecal samples from the Beijing Nanhaizi Père David's Deer Park and the Jiangsu Dafeng Père David's Deer National Nature Reserve between July 2010 and July 2011. Bacteria isolated using blood agar and mannitol agar plates were identified by Gram staining and nested PCR for 16S rRNA. We isolated C. perfringens from 41 fecal samples and used PCR amplification of five toxin genes to identify the toxinotypes and the cpe(+) strains of C. perfringens. Twenty-one isolates were type A, 15 were type E, and five were type D. Fifteen isolates were cpe(+) strains, including eight that were type A and seven that were type E.
Many higher plants of economic and biological importance undergo apomixis in which the maternal tissue of the ovule forms a seed, without experiencing meiosis and fertilization. This feature of apomixis has made it difficult to perform linkage mapping which relies on meiotic recombination. Here, we describe a computational model for mapping quantitative trait loci (QTLs) that control complex traits in apomictic plants. The model is founded on the mixture model-based likelihood in which maternal genotypes are dissolved into two possible components generated by meiotic and apomictic processes, respectively. The EM algorithm was implemented to discern meiotic and apomictic genotypes and, therefore, allow the marker-QTL linkage relationship to be estimated. By capitalizing on reciprocal crosses, the model is renovated to estimate and test imprinting effects of QTLs, providing a better gateway to characterize the genetic architecture of complex traits. The model was validated through computer simulation and further demonstrated for its usefulness by analyzing a real data for an apomictic woody plant. The model has for the first time provided a unique tool for genetic mapping in apomictic plants.
The aim of the present study was to investigate the differentially expressed genes (DEGs) and target genes of the estrogen receptor (ER) in renal cell carcinoma. The data (GSE12090) were downloaded from the gene expression omnibus database. Data underwent preprocessing using the affy package for Bioconductor software, then the DEGs were selected via the significance analysis of microarray algorithm within the siggenes package. Subsequently, the DEGs underwent functional and pathway enrichment analysis using Database for Annotation Visualization and Integrated Discovery software. Following data analysis, transcriptional regulatory networks between the DEGs and transcription factors were constructed. Finally, the ER target genes were subjected to gene ontology enrichment analysis. A total of 215 DEGs were identified between the chromophobe renal cell carcinoma samples and the oncocytoma samples, including 126 upregulated and 89 downregulated genes. Functional enrichment analysis indicated that 25% of the DEGs were significantly enriched in functions associated with the plasma membrane. Among those DEGs, 105 were regulated by the ER. Further regulatory network analysis indicated that the ER was mainly involved in the regulation of oncogenes and tumor suppressor genes, including protease serine 8, claudin 7 and Ras?related protein Rab?25. In the present study, the identified ER target genes were demonstrated to be closely associated with tumor development; this knowledge may improve the understanding of the ER regulatory mechanisms during tumor development and promote the discovery of predictive markers for renal cell carcinoma.
Interleukin (IL)-21, a cytokine produced by activated CD4(+) T cells, has broad pleiotropic actions that affect the functions of a variety of lymphoid cells. The roles of IL-21 in modulating immunity to infections are currently being defined. Notably, IL-21-mediated cellular and humoral immune responses play an important role in determining the outcome of viral infection. This article reviews the current knowledge on the critical role of IL-21 in hepatitis B virus (HBV) infection. As a competent intermediary, IL-21 derived from virus-specific CD4(+) T cells plays key roles in sustaining CD8(+) T cells and promoting B-cell responses that are essential for effective viral control. However, as a mediator of inflammation, IL-21 is also involved in the development of HBV-induced liver cirrhosis and exacerbating liver injury. Overall, the current data point to IL-21 as an immunomodulatory cytokine in HBV infection. Immunotherapeutic strategies aimed at optimizing the beneficial effects of IL-21 in HBV infection may prove to be a rigorous challenge in the future, as they should foster the strengths of IL-21 while circumventing potential drawbacks.Cellular & Molecular Immunology advance online publication, 3 November 2014; doi:10.1038/cmi.2014.109.
The type 1 insulin-like growth factor receptor (IGF-1R) is a promising target for cancer therapy with antibodies and small molecule tyrosine kinase inhibitors (TKIs) which have been actively tested clinically. Evidences have demonstrated that insulin receptor (IR), which is implicated in tumorigenesis, conveys resistance to IGF-1R targeted therapy. This provided the compelling rationale for co-targeting IGF-1R and IR. Herein we have developed an approach to simultaneously down-regulate IGF-1R and IR in protein levels. By generating and screening several engineered ubiquitin ligases, we have identified that, PTB-U-box, which is composed of an IGF-1R/IR-binding domain and a functional E3 ubiquitin ligase domain, binds activated IGF-1R/IR and targets their ubiquitination and degradation. When ectopically expressed in HepG2 and HeLa cells, PTB-U-box inhibits cell proliferation and invasion, increases chemo-sensitivity, as well as interrupts glucose metabolism. Finally, intratumoral injection of adenovirus carrying PTB-U-box dramatically retards the growth of HepG2 xenograft. Therefore, well-designed engineered ubiquitin ligase represents an effective therapeutic strategy for the treatment of the cancers with co-expressed IGF-1R/IR.
To investigate the clinical epidemiologic characteristics and analyze risk factors for acute respiratory syncytial virus (RSV) infection in hospitalized infants with acute lower respiratory tract infection (ALRI).
Recent work on statistical learning has demonstrated that environmental regularities can influence aspects of perception, such as familiarity judgments. Here, we ask if statistical co-occurrences accumulated from visual statistical learning could form objects that serve as the units of attention (i.e., object-based attention). Experiment 1 demonstrated that, after observers first viewed pairs of shapes that co-occurred in particular spatial relationships, they were able to recognize the co-occurring pairs, and were faster to discriminate two targets when they appeared within a learned pair ("object") than when the targets appeared between learned pairs, demonstrating an equivalent of an object-based attention effect. Experiment 2 replicated the results of Experiment 1 using a different set of shape pairs, and revealed a negative association between the attention effect and familiarity judgments of the co-occurred pairs. Experiment 3 reports three control experiments that validated the task procedure and ruled out alternative accounts.
A new kind of optofluidic in-fiber integrated device based on a specially designed hollow optical fiber with an inner core is designed. The inlets and outlets are built by etching the surface of the optical fiber without damaging the inner core. A reaction region between the end of the fiber and a solid point obtained after melting is constructed. By injecting samples into the fiber, the liquids can form steady microflows and react in the region. Simultaneously, the emission from the chemiluminescence reaction can be detected from the remote end of the optical fiber through evanescent field coupling. The concentration of ascorbic acid (AA or vitamin C, Vc) is determined by the emission intensity of the reaction of Vc, H2O2, luminol, and K3Fe(CN)6 in the optical fiber. A linear sensing range of 0.1-3.0 mmol L(-1) for Vc is obtained. The emission intensity can be determined within 2 s at a total flow rate of 150 ?L min(-1). Significantly, this work presents information for the in-fiber integrated optofluidic devices without spatial optical coupling.
Spiroplasma eriocheiris is as a novel pathogen of Chinese mitten crab Eriocheir sinensis tremor disease. The hemocytes have been shown to be major target cells in S. eriocheiris infection. The aim of this study was to examine the hemocytes' immune response at the protein levels. The differential proteomes of the crab hemocytes were analyzed immediately prior to injection with the pathogen, and at 10 d post-injection by isobaric tags for relative and absolute quantization (iTRAQ) labeling, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 1075 proteins were identified by LC-MS/MS and de novo sequencing data. Using a 1.2-fold change in expression as a physiologically significant benchmark, 76 differentially expressed proteins (7.07%) were reliably quantified by iTRAQ analysis. Thirty-five (3.26%) proteins were up-regulated and 41 (3.81%) proteins were down-regulated resulting from a S. eriocheiris infection. Approximately 20 differential proteins in hemocytes were involved in the stress and immune responses. Up-regulated proteins included alpha-2-macroglobulin (?2M), prostaglandin D synthase (GST), ferritin, and heat shock protein 60. Down-regulated proteins included two lectins (mannose-binding protein and hemocytin), three kinds of serine proteinase inhibitors (two serpins and pacifastin), three different kinds of serine proteases, mitogen-activated protein kinase kinase (MAPKK), and two thioredoxins (Trx), crustin, etc. Selected bioactive factors (?2M, GST, ferritin, tubulin, crustin, thioredoxin, clip domain serine protease and serpin) are verified by their immune roles in the S. eriocheiris infection using Real-time PCR. The variation trend of immune gene's mRNA expression is similar with the result of iTRAQ, except the tubulin. The prophenoloxidase-activating system, antimicrobial action and antioxidant system involved in the immune responses of E. sinensis is believed to be a resistance to S. eriocheiris infection. This is the first report of the proteome response of crab hemocytes against S. eriocheiris infection. These findings contribute to our understanding of tremor disease processes in crabs, and provide the first evidence to promote a search for potential biomarkers of the disease.
We demonstrate a semi-open cavity in-fiber Mach-Zehnder interferometer based on optical fiber tube (OFT) for temperature measurement with high sensitivity. The interferometer is composed of an OFT sandwiched between two multimode fibers, with lateral offset. The air hole of the OFT was not completely sealed and liquid is poured into the air hole through the unsealed gap. Light from the multimode fiber is split into two beams: one beam transmits directly through the silica tube while the other travels along the liquid-filled cavity. The device has ultra-high temperature sensitivity due to the much larger thermo-optic coefficient of the liquid compared with that of silica. Experimental results show that the temperature sensitivity is 6.35 nm/°C for an ethanol-filled structure.
We investigated the association between polymorphisms in excision repair cross-complementation group 1 (ERCC1) (rs3212986, rs2298881 and rs11615) and xeroderma pigmentosum-complementation group F (XPF) (rs2276466 and rs6498486) and risk of colorectal cancer. A 1:1 matched case-control study was conducted. Conditional regression analysis indicated that individuals carrying the ERCC1 rs3212986 TT genotype and T allele had a marginally increased risk of colorectal cancer when compared with subjects with the GG genotype. Similarly, subjects carrying the rs11615 TT genotype and T allele had a marginally increased risk of colorectal cancer when compared with those with the CC genotype. Stratified analysis revealed that individuals with rs3212986 TT who were current or former smokers had a significantly increased risk of colorectal cancer, and a significant interaction was found between this SNP and cigarette smoking. In conclusion, our study suggests that rs3212986 and rs11615 polymorphisms are associated with risk of colorectal cancer in a Chinese population, particularly in smokers. This finding could be useful in revealing the genetic characteristics of colorectal cancer, and suggests more effective strategies for prevention and treatment.
RNA-seq, based on deep-sequencing techniques, has been widely employed to precisely measure levels of transcripts and their isoforms expressed under different conditions. However, robust statistical tools used to analyze these complex datasets are lacking. By grouping genes with similar expression profiles across treatments, cluster analysis provides insight into gene functions and networks that have become increasingly important.
Compared with other Populus species, Populus euphratica Oliv. exhibits better tolerance to abiotic stress, especially those involving extreme temperatures. However, little is known about gene regulation and signaling pathways involved in low temperature stress responses in this species. Recent development of Illumina/Solexa-based deep-sequencing technologies has accelerated the study of global transcription profiling under specific conditions. To understand the gene network controlling low temperature perception in P. euphratica, we performed transcriptome sequencing using Solexa sequence analysis to generate a leaf transcriptome at a depth of 10 gigabases for each sample.
Recent studies have demonstrated that specific miRNAs, such as miR-221/222, may be responsible for tamoxifen resistance in breast cancer. Secreted miRNAs enclosed in exosomes can act as intercellular bio-messengers. Our objective is to investigate the role of secreted miR-221/222 in tamoxifen resistance of ER-positive breast cancer cells. Transmission electron microscopy analysis and nanoparticle tracking analysis were performed to determine the exosomes difference between MCF-7(TamR) (tamoxifen resistant) and MCF-7(wt) (tamoxifen sensitive) cells. PKH67 fluorescent labeling assay was used to detect exosomes derived from MCF-7(TamR) cells entering into MCF-7(wt) cells. The potential function of exosomes on tamoxifen resistance transmission was analyzed with cell viability, apoptosis ,and colony formation. MiRNA microarrays and qPCR were used to detect and compare the miRNAs expression levels in the two cells and exosomes. As the targets of miR-221/222, p27 and ER? were analyzed with western blot and qPCR. Compared with the MCF-7(wt) exosomes, there were significant differences in the concentration and size distribution of MCF-7(TamR) exosomes. MCF-7(wt) cells had an increased amount of exosomal RNA and proteins compared with MCF-7(TamR) cells. MCF-7(TamR) exosomes could enter into MCF-7(wt) cells, and then released miR-221/222. And the elevated miR-221/222 effectively reduced the target genes expression of P27 and ER?, which enhanced tamoxifen resistance in recipient cells. Our results are the first to show that secreted miR-221/222 serves as signaling molecules to mediate communication of tamoxifen resistance.
Substrate-mediated gene delivery is a promising method due to its unique ability to preconcentrate exogenous genes onto designated substrates. However, many challenges remain to enable continuous and multiround delivery of the gene using the same substrates without depositing payloads and immobilizing cells in each round of delivery. Herein we introduce a gene delivery system, nanosubstrate-mediated delivery (NSMD) platform, based on two functional components with nanoscale features, including (1) DNA?SNPs, supramolecular nanoparticle (SNP) vectors for gene encapsulation, and (2) Ad-SiNWS, adamantane (Ad)-grafted silicon nanowire substrates. The multivalent molecular recognition between the Ad motifs on Ad-SiNWS and the ?-cyclodextrin (CD) motifs on DNA?SNPs leads to dynamic assembly and local enrichment of DNA?SNPs from the surrounding medium onto Ad-SiNWS. Subsequently, once cells settled on the substrate, DNA?SNPs enriched on Ad-SiNWS were introduced through the cell membranes by intimate contact with individual nanowires on Ad-SiNWS, resulting in a highly efficient delivery of exogenous genes. Most importantly, sequential delivery of multiple batches of exogenous genes on the same batch cells settled on Ad-SiNWS was realized by sequential additions of the corresponding DNA?SNPs with equivalent efficiency. Moreover, using the NSMD platform in vivo, cells recruited on subcutaneously transplanted Ad-SiNWS were also efficiently transfected with exogenous genes loaded into SNPs, validating the in vivo feasibility of this system. We believe that this nanosubstrate-mediated delivery platform will provide a superior system for in vitro and in vivo gene delivery and can be further used for the encapsulation and delivery of other biomolecules.
A compact all-fiber plasmonic Airy-like beam generator is demonstrated. A single slit and a 1D groove array were fabricated by focused ion beam milling on the gold deposited end facet of a single-mode optical fiber. The single slit excites the surface plasmonic polaritons (SPPs), which are decoupled into free space by the groove array. The phase of decoupling SPPs is adjusted by the grooves position. Experimental generation of the single Airy-like beam has good consistency with theoretical predictions. The transverse acceleration and nondiffraction properties are observed. The interference of double Airy-like beams in the free space is also analyzed. The presented plasmonic Airy-like beam generator is of importance to realize all-fiber optical trapping, beam shaping, and fiber integrated devices.
Fundamental core-mode cutoff and evanescent field are considered for an eccentric core optical fiber (ECOF). A method has been proposed to calculate the core-mode cutoff by solving the eigenvalue equations of an ECOF. Using conformal mapping, the asymmetric geometrical structure can be transformed into a simple, easily solved axisymmetric optical fiber with three layers. The variation of the fundamental core-mode cut-off frequency (V(c)) is also calculated with different eccentric distances, wavelengths, core radii, and coating refractive indices. The fractional power of evanescent fields for ECOF is also calculated with the eccentric distances and coating refractive indices. These calculations are necessary to design the structural parameters of an ECOF for long-distance, single-mode distributed evanescent field absorption sensors.
A compact single-mode photonic crystal fiber single-mode fiber tip (SPST) refractive index sensor is demonstrated in this Letter. A CO2 laser cleaving technique is utilized to provide a clean-cut fiber tip, which is then coated by a layer of gold to increase reflection. An average sensitivity of 39.1 nm/RIU and a resolvable index change of 2.56×10(-4) are obtained experimentally with a ?3.2 ?m diameter SPST. The temperature dependence of this fiber-optic sensor probe is presented. The proposed SPST refractometer is also significantly less sensitive to temperature and an experimental demonstration of this reduced sensitivity is presented in the Letter. Because of its compactness, ease of fabrication, linear response, low temperature dependency, easy connectivity to other fiberized optical components and low cost, this refractometer could find various applications in chemical and biological sensing.
In this article, we reviewed the interactions between dendrimers and surfactants with particular focus on the interaction mechanisms and physicochemical properties of the yielding dendrimer-surfactant aggregates. In order to provide insight into the behavior of dendrimers in biological systems, the interactions of dendrimers with bio-surfactants such as phospholipids in bulk solutions, in solid-supported bilayers and at the interface of phases or solid-states were discussed. Applications of the dendrimer-surfactant aggregates as templates to guide the synthesis of nanoparticles and in drug or gene delivery were also mentioned.
Glioma is the most common primary brain tumor among adults. Temozolomide (TMZ) is widely used as the first?line postsurgical drug for malignant glioma. However, the therapeutic efficacy of TMZ remains ineffective as inherited or acquired drug resistance is frequently observed. Estrogen receptor ? (ER?) has emerged as a tumor suppressor and a key regulator of signal transduction in glioma cells. However, little is known about the role of ER? in regulating the chemotherapeutic response to TMZ. In the current study, the TMZ?resistant U138 glioma cells were treated with the novel ER? agonist liquiritigenin (Liq). It was observed that Liq significantly enhanced ER? expression and sensitized glioma cells to TMZ?induced proliferation inhibition. As a potential mechanism, it was noted that Liq treatment significantly inhibited the activity of the PI3K/AKT/mTOR pathway, which played a protective role against the TMZ?induced cytotoxicity. In addition, it was demonstrated that ER? knockdown or activation of the phosphatidylinositol?4,5?bisphosphate 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway by insulin?like growth factor 1 both eradicated the function of Liq. These results suggest that Liq treatment enhances glioma cell susceptibility to TMZ by inhibiting the PI3K/AKT/mTOR pathway. As hyperactivation of the PI3K/AKT/mTOR pathway is frequently observed in gliomas, the combined use of ER? agonists may become a feasible therapy option to overcome chemoresistance to TMZ.
Neonatal mortality reduction in China over past two decades was reported from nationwide sampling surveys, however, how high risk pregnancy affected neonatal outcome is unknown. The objective of this study was to explore relations of pregnancy complications and neonatal outcomes from a regional birth population.
N?myc downstream regulated gene 2 (NDRG2) is highly expressed in numerous normal tissues, while it is marginally expressed or undetectable in various tumors, including lung and colon cancer. In order to investigate the expression of NDRG2 in human glioma and its downstream regulatory mechanisms, quantitative polymerase chain reaction (qPCR), immunohistochemistry and western blot analyses were used to assess NDRG2 mRNA and protein expression in different grades of human glioma and adjacent normal tissues. The methylation status of the NDRG2 promoter region was also determined using bisulfite sequencing. NDRG2 mRNA expression was observed to be significantly lower in glioma tissues than in adjacent normal tissues (P<0.05). Furthermore, a significant negative correlation was found between the glioma tumor grade and NDRG2 expression (P<0.05), at the mRNA and protein levels. Moreover, the methylation rate of the NDRG2 promoter region was 46.3% in the glioma tissues compared with 18.2% in the adjacent normal tissues (P<0.05). These findings show that NDRG2 expression is downregulated in human glioma and that the level of NDRG2 expression negatively correlates with the glioma grade. Furthermore, these findings indicate that NDRG2 downregulation may be due to aberrant methylation of the NDRG2 promoter region and subsequent transcriptional inactivation.
N-myc downstream-regulated gene 2 (NDRG2), a novel tumour suppressor and cell stress-related gene, is involved in many cell metabolic processes, such as hormone, ion and fluid metabolism. We investigated whether NDRG2 is involved in any glucose-dependent energy metabolism, as well as the nature of its correlation with breast carcinoma.
Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro.
We propose and numerically analyze the transverse acceleration control for the Airy-like beams from incomplete Airy waveguide and Airy waveguide by rainbow effect. We show that the Airy-like beams have an obvious change in transverse acceleration with a slight variation (10 nm) in incident wavelength. The rainbow phenomenon is introduced to study the Airy-like beam propagation with a different wavelength. The equivalent initial launch angle is also considered to explain transverse acceleration of the Airy-like beams.
Discoidin domain receptor 2 (DDR2), a collagen receptor tyrosine kinase, initiates signal transduction upon collagen binding, but little is known as to how DDR2 signaling is negatively regulated. Herein we demonstrate that Cbl family member Cbl-b predominantly promotes the ubiquitination of DDR2 upon collagen II stimulation. Cbl-b-mediated ubiquitination accelerates the degradation of activated DDR2. Finally, the production of MMP-13, a downstream target of DDR2, is enhanced in Cbl-b-knocked down MC3T3-E1 cells and Cbl-b-deficient mouse primary synovial fibroblasts. Thus, Cbl-b, by promoting the ubiquitination and degradation of DDR2, functions as a negative regulator in the DDR2 signaling pathway.
Choroidal neovascularization (CNV), an aberrant growth of blood vessels in the choroid layer of the eye, is a major cause of vision loss. In view of our recent finding that discoidin domain receptor 2 (DDR2), a collagen-binding receptor tyrosine kinase, is involved in control of vascular endothelial activity and tumor angiogenesis, the present study aims to investigate whether and how DDR2 affects the pathogenesis of CNV. We initially found that a spontaneous DDR2 mutant mouse colony (slie) exhibited enhanced amplitude of laser-induced CNV. The inhibitory role of DDR2 in CNV development was further confirmed by experiments through intravitreous injection of DDR2 small interference RNA (siRNA) or DDR2-expressing adenovirus. Quantitative real-time polymerase chain reaction (qPCR) and immunoblot analysis showed that DDR2 regulates the expression of several major pro-angiogenic factors in the laser-injured choroid as well as in retinal pigment epithelium (RPE) cells. In addition, it was demonstrated that the CNV-induced increases in the phosphorylation levels of Akt and mTOR were affected by the upregulation or downregulation of DDR2. Thus, the data from this study for the first time revealed that DDR2 negatively regulates the development of experimental CNV in vivo, which may provide a novel target for preventing human pathological ocular neovascularization.
Although glucosamine has been suggested to be effective in the treatment of osteoarthritis, its effect on disc degeneration remains unclear. We sought to explore whether glucosamine can activate autophagy in rat nucleus pulposus (NP) cells and protect cells treated with IL-1? or hydrogen peroxide (H2 O2 ). Autophagy in cells was examined by detecting for LC3, Beclin-1, m-TOR, and p70S6K, as well as by analyzing autophagosomes. To inhibit autophagy, 3-methyladenine (3-MA) was used. In the cells treated with IL-1?, the levels of Adamts-4, Mmp-13, aggrecan, and Col2a1 were analyzed by real-time PCR and immunofluorescence. Apoptosis was analyzed by TUNEL. Cell senescence under H2 O2 was revealed by SA-?-Gal staining. Glucosamine could activate autophagy in a dose-dependent manner within 24?h and inhibit the phosphorylation of m-TOR and p70S6K. Autophagy in IL-1? or H2 O2 -treated cells was increased by glucosamine. Glucosamine attenuated the decrease of aggrecan and prevented the apoptosis of the NP cells induced by IL-1?, whereas 3-MA partly reversed these effects. The percentage of SA-?-Gal-positive cells induced by H2 O2 treatment was decreased by glucosamine, accompanied by the decline of p70S6K phosphorylation. Glucosamine protects NP cells and up-regulates autophagy by inhibiting the m-TOR pathway, which might point a potential therapeutic agent for disc degeneration.
The molecular mechanism that regulates epicardial development has yet to be understood. In this study, we explored the function of CDX1, a Caudal-related family member, in epicardial epithelial-to-mesenchymal transition (EMT) and in the migration and the differentiation of epicardium-derived progenitors into vascular smooth muscle cells. We detected a transient expression of CDX1 in murine embryonic hearts at 11.5 days post coitum (dpc). Using a doxycycline-inducible CDX1 mouse model, primary epicardium, and ex vivo heart culture, we further demonstrated that ectopic expression of CDX1 promoted epicardial EMT. In addition, a low-dose CDX1 induction led to enhanced migration and differentiation of epicardium-derived cells into ?-SMA+ vascular smooth muscles. In contrast, either continued high-level induction of CDX1 or CDX1 deficiency attenuated the ability of epicardium-derived cells to migrate and to mature into smooth muscles induced by TGF-?1. Further RNA-seq analyses showed that CDX1 induction altered the transcript levels of genes involved in neuronal development, angiogenesis, and cell adhesions required for EMT. Our data have revealed a previously undefined role of CDX1 during epicardial development, and suggest that transient expression of CDX1 promotes epicardial EMT, whereas subsequent down-regulation of CDX1 after 11.5 dpc in mice is necessary for further subepicardial invasion of EPDCs and contribution to coronary vascular endothelium or smooth muscle cells.
Current histopathological classification and TNM staging have limited accuracy in predicting survival and stratifying patients for appropriate treatment. The goal of the study is to determine whether the expression pattern of functionally important regulatory proteins can add additional values for more accurate classification and prognostication of non-small lung cancer (NSCLC).
Circulating tumor cells (CTCs) in the blood which have detached from both the primary tumor and any metastases may be considered as a "liquid biopsy" and are expected to replace tumor biopsies in the monitoring of treatment response and determining patient prognosis. Here, we introduce a facile and efficient CTC detection material made of hydroxyapatite/chitosan (HA/CTS), which is beneficial because of its transparency and excellent biological compatibility. Atomic force microscopy images show that the roughness of the HA/CTS nanofilm (HA/CTSNF) substrates can be controlled by changing the HA:CTS ratio. Enhanced local topographic interactions between nano-components on cancer cell membranes, and the antibody coated nanostructured substrate lead to improved CTC capture and separation. This remarkable nanostructured substrate has the potential for CTC culture in situ and merits further analysis. CTCs captured from artificial blood samples were observed in culture on HA/CTSNF substrates over a period of 14 days by using conventional staining methods (hematoxylin eosin and Wright's stain). We conclude that these substrates are multifunctional materials capable of isolating and culturing CTCs for subsequent studies.
We propose and demonstrate a two-dimensional (2D) Airy-like beam generation technique based on arrayed waveguides. We show that the output beams with quasi-Airy amplitude and cubic-like phase from an arrayed waveguide end have 2D Airy-like patterns. These beams have the ability to remain quasi-nondiffracting, transverse accelerating, and self-healing during propagation. We also analyze wave propagation along this arrayed waveguide using coupled-mode theory and the beam propagation method.
Apolipoprotein A-I (apoA-I) has a great conformational flexibility to exist in lipid free, lipid poor and lipid bound states during lipid metabolism. To address the lipid binding and the dynamic desorption behavior of apoA-I at lipoprotein surfaces, apoA-I, ?(185-243)apoA-I and ?(1-59)(185-243)apoA-I were studied at triolein/water and phosphatidylcholine/triolein/water interfaces with special attention to surface pressure. All three proteins are surface active to both interfaces lowering the interfacial tension and thus increasing the surface pressure to modify the interfaces. ?(185-243)apoA-I adsorbs much more slowly and lowers the interfacial tension less than full-length apoA-I confirming that the C-terminal domain (residues 185-243) initiates the lipid binding. ?(1-59)(185-243)apoA-I binds more rapidly and lowers the interfacial tension more than ?(185-243)apoA-I suggesting that destabilizing the N-terminal ?-helical bundle (residues 1-185) restores lipid binding. The three proteins desorb from both interfaces at different surface pressures revealing that different domains of apoA-I possess different lipid affinity. ?(1-59)(185-243)apoA-I desorbs at lower pressures compared to apoA-I and ?(185-243)apoA-I indicating that it is missing a strong lipid association motif. We propose that during lipoprotein remodeling, surface pressure mediates the adsorption, partial or full desorption of apoA-I allowing it to exchange among different lipoproteins and adopt various conformations to facilitate its multiple functions.
Searching for reversible hydrogen storage materials operated under ambient conditions is a big challenge for material scientists and chemists. In this work, using density functional calculations, we systematically investigated the hydrogen storage properties of the two-dimensional (2D) Ti2C phase, which is a representative of the recently synthesized MXene materials ( ACS Nano 2012 , 6 , 1322 ). As a constituent element of 2D Ti2C phase, the Ti atoms are fastened tightly by the strong Ti-C covalent bonds, and thus the long-standing clustering problem of transition metal does not exist. Combining with the calculated binding energy of 0.272 eV, ab initio molecular dynamic simulations confirmed the hydrogen molecules (3.4 wt % hydrogen storage capacity) bound by Kubas-type interaction can be adsorbed and released reversibly under ambient conditions. Meanwhile, the hydrogen storage properties of the other two MXene phases (Sc2C and V2C) were also evaluated, and the results were similar to those of Ti2C. Therefore, the MXene family including more than 20 members was expected to be a good candidate for reversible hydrogen storage materials under ambient conditions.
L-DNA is the mirror-image form of natural D-DNA. We demonstrate that one left-handed G-rich sequence can form an L-DNA intramolecular G-quadruplex. Further investigation revealed that a DNAzyme formed by an L-nucleotide G-quadruplex exhibited peroxidase catalytic efficiency. The enhancement of the color change of the oxygenation product ABTS(•-) caused by L-nucleotide G-quadruplex formation could be clearly observed with naked eyes. This research provides a new concept for the application of the L-DNA peroxidase DNAzyme complex in nuclease-containing biological systems.
Two novel porous copper-based metal-organic frameworks with nbo and agw topologies have been designed and synthesized using tetracarboxylate and tricarboxylate ligands, respectively. They possess large surface areas and high CO2 adsorption capacities (up to 170 cm(3)/g or 7.59 mmol/g at 0 °C under ambient pressure).
We report an in-fiber integrated chemiluminiscence (CL) sensor based on a kind of hollow optical fiber with a suspended inner core. The path of microfluid is realized by etching microholes for inlets and outlets on the surface of the optical fiber without damaging the inner core and then constructing a melted point beside the microhole of the outlet. When samples are injected into the fiber, the liquids can be fully mixed and form steady microflows. Simultaneously, the photon emitted from the CL reaction is efficiently coupled into the core and can be detected at the end of the optical fiber. In this Letter, the concentration of H2O2 samples is analyzed through the emission intensity of the CL reaction among H2O2, luminol, K3Fe(CN)6, and NaOH in the optical fiber. The linear sensing range of 0.1-4.0 mmol/L of H2O2 concentration is obtained. The emission intensity can be determined within 400 ms at a total flow rate of 150 ?L/min. Significantly, this work presents the information of developing in-fiber integrated online analyzing devices based on optical methods.
We demonstrate trapped yeast cell axial-position adjustment without moving the optical fiber in a single-fiber optical trapping system. The dynamic axial-position adjustment is realized by controlling the power ratio of the fundamental mode beam (LP01) and the low-order mode beam (LP11) generated in a normal single-core fiber. In order to separate the trapping positions produced by the two mode beams, we fabricate a special fiber tapered tip with a selective two-step method. A yeast cell of 6 ?m diameter is moved along the optical axis direction for a distance of ~3 ?m. To the best of our knowledge, this is the first demonstration of the trapping position adjustment without moving the fiber for single-fiber optical tweezers. The excitation and utilization of multimode beams in a single fiber constitutes a new development for single-fiber optical trapping and makes possible more practical applications in biomedical research fields.
We propose and demonstrate a approach for Airy-like wave generation using one-dimensional arrayed waveguides instead of a cubic phase plate and a Fourier lens. We show that this Airy-like wave with quasi-Airy amplitude and quasi-cubic phase from arrayed waveguides end has abilities to remain quasi-nondiffracting and freely accelerating during propagation. We also study wave propagation in these waveguides based on supermode theory and beam propagation method. The numerical results are in good agreement with theoretical prediction.
In-line rainbow trapping is demonstrated in an optical microfiber with a plasmonic grating. The dispersions of x- and y-polarized surface plasmon polariton (SPP) modes are analyzed in detail by the 3D finite element method (FEM). In this system, the incident light is coupled from an optical microfiber into a graded grating. The plasmonic structure shows strong localization as the dispersion curve approaches cut-off frequency. Gradually increasing the depth or width of the grating elements ensures that the cut-off frequency of the SPP mode varies with the position along the microfiber. Near-infrared light at different frequencies can be trapped in different spatial positions. The in-line rainbow trapping is important for potential applications including optical storage, slow light, optical switch and enhanced light-matter interactions in fiber integrated devices and highly integrated optical circuits.
To characterize the endothelial progenitor cell mobilization in the models of moderate and severe lung injury, we hypothesized that there were differences in endothelial progenitor cell levels and mobilizing cytokines between moderate and severe lung injury.
Three lactam compounds were isolated from the fruiting body of Tricholoma matsutake (S. Ito & Imai) Sing., an edible mushroom, and their structures were identified as cyclo-S-proline-R-leucine (1), hexahydro-2H-azepin-2-one (2), and butyl 5-oxo-2-pyrrolidine carboxylate (3) by chemical, physicochemical, and spectral evidence. In in vitro screening tests, compounds 1 and 2 acted as calcium sensitizers in ventricular cells from rat. Further studies on compounds 1 and 2 in ex vivo isolated right atria showed positive inotropic effects without disturbing the spontaneous beating rate. The inotropic effect of compounds 1 and 2 could be greatly abolished by pretreating the myocardium in Ca(2+)-free solution. These findings indicate that compounds 1 and 2 can significantly increase the calcium ion concentration ([Ca2+]i) in myocytes, which is greatly dependent on the influx of extracellular Ca2+.
One of the most common oral manifestations of menopause is xerostomia. Oral dryness can profoundly affect quality of life and interfere with basic daily functions, such as chewing, deglutition, and speaking. Although the feeling of oral dryness can be ameliorated after estrogen supplementation, the side effects of estrogen greatly restrict its application. We previously found that N-myc downstream-regulated gene 2 (NDRG2) is involved in estrogen-mediated ion and fluid transport in a cell-based model. In the present study, we used an ovariectomized rat model to mimic xerostomia in menopausal women and constructed two adenovirus vectors bearing NDRG2 to validate their therapeutic potential. Ovariectomized rats exhibited severe sialaden hypofunction, including decreased saliva secretion and ion reabsorption as well as increased water intake. Immunohistochemistry revealed that the expression of NDRG2 and Na(+) reabsorption-related Na(+)/K(+)-ATPase and ENaC decreased in ovariectomized rat salivary glands. We further showed that the localized delivery of NDRG2 improved the dysfunction of Na(+) and Cl(-) reabsorption. In addition, the saliva flow rate and water drinking recovered to normal. This study elucidates the mechanism of estrogen deficiency-mediated xerostomia or sialaden hypofunction and provides a promising strategy for therapeutic intervention.Molecular Therapy (2013); doi:10.1038/mt.2013.286.
A zeolitic metal-organic framework with a SOD topology, (Et2NH2)[In(BCBAIP)]·4DEF·4EtOH (H4BCBAIP: 5-(bis(4-carboxybenzyl)amino)isophthalic acid) (1), has been constructed by a 4 + 4 synthetic strategy from tetrahedral organic building units and In(3+) ions. Compound 1 could adsorb organic dyes and be used as a light-harvesting antenna.
We demonstrate the isolation of circulating tumor cells (CTCs) with a biocompatible nano-film composed of TiO2 nanoparticles. Due to the enhanced topographic interaction between nano-film and cancer cell surface, cancer cells (HCT116) spiked into PBS and healthy blood can be recovered from the suspension, whose efficiencies were respectively 80 % and 50 %. Benifit from the biocompatibility of this nano-film, in-situ culture of the captured cancer cells is also available, which provides an alternative selection when the capture cell number was inadequate or the sample cannot be analyzed immediately. For the proof-of-concept study, we use this nano-film to separate the circulating tumor cells from the colorectal and gastric cancer patient peripheral blood samples and the captured CTCs are identified by a three-colored immunocytochemistry method. We investigated the cancer cells capture strength at the nano-bio interface through exposing the cells to fluid shear stress in microfluidic device, which can be utilized to increase the purity of CTCs. The result indicated that 50 % of the captured cells can be detached from the substrate when the fluid shear stress was 180 dyn cm(-2). By integration of this CTCs capture nano-film with other single cell analysis device, we expected to further explore their applications in genome sequencing based on the captured CTCs.
Early cerebral infarction (ECI) following aneurysmal subarachnoid hemorrhage (aSAH) remains poorly understood. This study aims to determine the frequency and risk factors of this special episode, as well as to assess the relationship between its patterns and outcome. We retrospectively enrolled 243 patients who underwent aneurysm treatment within 60 hours of SAH. ECI was defined as one or more new hypodense abnormalities on computed tomography within 3 days after SAH, rather than lesions attributable to edema, retraction effect, and ventricular drain placement. Risk factors were tested by multivariate analysis. The infarct was classified by an established grading system (single or multiple, cortical or deep or combined). Poor outcome was defined as the Glasgow Outcome Score of severe disability or worse. Sixty-five patients (26.7%) had early infarction. Acute hydrocephalus (odds ratio [OR] 6.67; 95% confidence interval [CI] 1.59-27.95), admission plasma glucose level (OR 1.42 per mmol/L; 95% CI 1.16-1.73), and treatment modality (OR 16.27; 95% CI 4.05-65.28) were independent predictors of ECI. The pattern was single cortical in 19 patients (29.2%), single deep in 9 (13.8%), multiple cortical in 8 (12.3%), multiple deep in 14 (21.5%), and multiple combined in 15 (23.1%). ECI was associated with delayed cerebral infarction (DCI) (P = 0.002) and poor outcome (P < 0.001). Multiple combined infarction was related to poor outcome (P = 0.001). In summary, the occurrence of ECI, which is associated with surgical treatment, acute hydrocephalus and high admission plasma glucose, may potentially predict DCI and unfavorable outcome. Further studies are warranted to reveal the underlying mechanisms of this event and thereby minimize it.
Alpinetin is a natural flavonoid that protects cells against fatal injury in ischemia-reperfusion. ? receptor activation protects myocardial cells from trauma; however, the mechanism is unknown. The aim of this study was to explore the function of alpinetin in ? receptor-mediated myocardial apoptosis. The myocardial cells of newly born rats were cultivated and myocardial apoptosis was induced by serum deprivation. The MTT method was used to evaluate cell viability and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining was used to analyze apoptosis. The expression levels of opioid receptor mRNA and protein were tested using reverse transcription-polymerase reaction (RT-PCR) and western blot assays. In addition, an opioid receptor antagonist, as well as protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) inhibitors, were used to determine the inferred signaling pathway. The results showed that that alpinetin reduced the myocardial apoptosis induced by serum deprivation in a concentration-dependent manner. However, the protection conferred to the myocardial cells by alpinetin was blocked by the ? opioid receptor antagonist naltrindole, as well as by PKC and ERK inhibitors (GF109203X and U0126, respectively). In addition, it was shown that alpinetin was able to maintain the stability of the mitochondrial membrane potential, lower the level of intracytoplasmic cytochrome c and reduce Bax displacement from the cytoplasm to the mitochondria. It was concluded that alpinetin was able to activate ? receptors to induce the endogenous protection of myocardial cells via the PKC/ERK signaling pathway.
Recent studies have illuminated the diversity of roles for microRNAs in cellular, developmental, and pathophysiological processes. The study of microRNAs in human liver tissue promises to clarify the therapeutic and diagnostic value of this important regulatory mechanism of gene expression.
Amphipathic ?-helices mediate binding of exchangeable apolipoproteins to lipoproteins. To probe the role of ?-helical structure in protein-lipid interactions, we used oil-drop tensiometry to characterize the interfacial behavior of apolipoprotein C-I (apoC-I) variants at triolein/water (TO/W) and 1-palmitoyl-2-oleoylphosphatidylcholine/triolein/water (POPC/TO/W) interfaces. ApoC-I, the smallest apolipoprotein, has two amphipathic ?-helices. Mutants had single Pro or Ala substitutions that resulted in large differences in helical content in solution and on phospholipids. The ability of apoC-I to bind TO/W and POPC/TO/W interfaces correlated strongly with ?-helical propensity. On binding these interfaces, peptides with higher helical propensity increased surface pressure to a greater extent. Likewise, peptide exclusion pressure at POPC/TO/W interfaces increased with greater helical propensity. ApoC-I retention on TO/W and POPC/TO/W interfaces correlated strongly with phospholipid-bound helical content. On compression of these interfaces, peptides with higher helical content were ejected at higher pressures. Substitution of Arg for Pro in the N-terminal ?-helix altered net charge and reduced apoC-I affinity for POPC/TO/W interfaces. Our results suggest that peptide-lipid interactions drive ?-helix binding to and retention on lipoproteins. Point mutations in small apolipoproteins could significantly change ?-helical propensity or charge, thereby disrupting protein-lipid interactions and preventing the proteins from regulating lipoprotein catabolism at high surface pressures.
Carboxymethyl ?-carrageenan (CM?C)/alginate (AL) blend fibers were prepared by spinning their mixture solution through a viscose-type spinneret into a coagulating bath containing aqueous CaCl2 and ethanol. The structure and properties of blend fibers were studied with the aid of infrared spectroscopy, scanning electron microscopy, X-ray diffraction, and thermogravimetric analysis. The analyses indicated a good miscibility between AL and CM?C because of the strong interaction of the intermolecular hydrogen bonds. The mechanical properties and water-retention properties were also measured. The best values of tensile strength and breaking elongation were obtained when CM?C content was 30 wt.%. The water-retention properties and thermostability improved by blending method. Antibacterial fibers, obtained by the treatment of the fibers with an aqueous solution of silver nitrate, exhibited good antibacterial activity to Staphylococcus aureus.
Given the clinical significance of hepatitis B e antigen (HBeAg) seroconversion in chronic hepatitis B virus (HBV) infection, it is critical to elucidate the mechanisms regulating this process. In the present study, we found that the frequency of circulating chemokine (C-X-C motif) receptor 5 (CXCR5)(+) CD4(+) T cells was higher in patients who had achieved HBeAg seroconversion in both cross-sectional (P?0.001) and longitudinal (P = 0.009) studies. These cells were able to produce a significantly higher level of intracellular interleukin 21 (IL-21) after stimulation with HBV peptides in patients with telbivudine-induced HBeAg seroconversion (P?=?0.007). Furthermore, sorted CXCR5(+) CD4(+) T cells from HBeAg seroconverters boosted a higher frequency of antibody against hepatitis B e antigen (anti-HBe)-secreting B cells in coculture assay (P?=?0.011). Of note, the increase in frequency of anti-HBe-secreting B cells was abrogated by soluble recombinant IL-21 receptor-Fc chimera (P?=?0.027), whereas exogenous recombinant IL-21 enhanced this effect (P?=?0.043). Additionally, circulating CXCR5(+) CD4(+) T cells shared similar phenotypic markers, and were positively correlated in frequency with, splenic follicular T helper cells. Conclusion: Circulating CXCR5(+) CD4(+) T cells, by producing IL-21, may have a significant role in facilitating HBeAg seroconversion in patients with chronic HBV infection.
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