Arisaematis Rhizoma (AR), a famous traditional Chinese medicine, has been widely used in Asia over thousands of years. Documented with noticeable toxicity in ancient books, AR has been used to treat various diseases in the clinic. Therefore, it is important to assess the toxicity of AR dynamically and holistically. In this study, a (1)H NMR-based metabolomics approach complemented with serum chemistry and histopathology has been applied to investigate the toxicity of AR. Rats were intragastrically administered with AR (0, 0.5 and 1 g kg(-1) body weight) for 30 days, and serum and urine samples were collected. Their (1)H NMR profiles were analyzed by multivariate pattern recognition techniques to denote metabolic variations induced by AR, and 13 metabolites in urine and 6 metabolites in serum were significantly altered, which suggested that disturbances in energy metabolism, perturbation of the gut microflora environment, membrane damage, folate deficiency and injury of kidneys are produced by AR. Histopathology showed a slight vacuolization of the glomerular matrix and edema of renal tubular epithelial cells in kidneys of AR administered rats, which were evidenced by increased levels of blood urea nitrogen and creatinine in serum chemistry. Our results indicated that oral administration of crude AR was found to induce slight renal toxicity. Therefore, precautions should be made to monitor the potential nephrotoxicity of AR in clinical use. The metabolomics approach provided a promising tool for the study and better understanding of TCM-induced toxicity dynamically and holistically.
In this work, we explore the existence of multiband localized spoof plasmons (LSPs) in closed textured cavities with multiple groove depths. It is interesting to note that the spoof LSPs in each band resemble those generated by the textured 2D cavities of the same periodicity with the corresponding single groove depth, and the field distributions and confinement characteristics of the plasmon-like modes in such a corrugated cavity are different from the conventional cavity. Hence, these multiple resonance band structures can find potential applications in the microwave and terahertz frequencies.
We proposed a novel biased optical Kerr gated imaging (BOKGI) method for ultrafast imaging. The imaging performance of the BOKGI system has been investigated. Experimental results showed that by using the BOKGI, the high spatial frequency components of the detected object could be effectively retrieved, which are often filtered by the photo-induced soft aperture in a conventional OKGI system. Comparing with the conventional OKGI method, the BOKGI method could enhance the sharpness of images and provide a higher spatial resolution of the imaging system. In addition, the influence of the biased angle on the BOKGI performance has been also investigated.
To introduce standard methods of scoring the data derived from both short and long form instruments of the International Physical Activity Questionnaire (IPAQ). The introduction part consists of a set of domains which include the structure of questionnaire, principles of data cleaning, calculation methods and grouping rules. Through practical experience, a specific calculation process of IPAQ-long based on the standard methods was showed.
Hydrophobic interaction has been considered to be responsible for adsorption of perfluorooctanesulfonate (PFOS) on the surface of hydrophobic adsorbents, but the long C-F chain in PFOS is not only hydrophobic but also oleophobic. In this study, for the first time we propose that air bubbles on the surface of hydrophobic carbonaceous adsorbents play an important role in the adsorption of PFOS. The level of adsorption of PFOS on carbon nanotubes (CNTs), graphite (GI), graphene (GE), and powdered activated carbon (PAC) decreases after vacuum degassing. Vacuum degassing time and pressure significantly affect the removal of PFOS by these adsorbents. After vacuum degassing at 0.01 atm for 36 h, the extent of removal of PFOS by the pristine CNTs and GI decreases 79% and 74%, respectively, indicating the main contribution of air bubbles to PFOS adsorption. When the degassed solution is recontacted with air during the adsorption process, the removal of PFOS recovers to the value obtained without vacuum degassing, further verifying the key role of air bubbles in PFOS adsorption. By theoretical calculation, the distribution of PFOS in air bubbles on the adsorbent surfaces is discussed, and a new schematic sorption model of PFOS on carbonaceous adsorbents in the presence of air bubbles is proposed. The accumulation of PFOS at the interface of air bubbles on the adsorbents is primarily responsible for its adsorption, providing a new mechanistic insight into the transport, fate, and removal of PFOS.
Abstract Hemibarbus is a genus of cyprinid fishes distributed in eastern Asia. In the present study, we report here the complete mitochondrial genome of the Hemibarbus sp.090914 (Cypriniformes: Cyprinidae). Our results show that the complete mitochondrial DNA of Hemibarbus sp.090914 is 16,610?bp in length, and predicted to encode all the 37 genes that are typical for the vertebrates.
Sphingosylphosphorylcholine (SPC) is a bioactive lipid mediated popular cell apoptosis in cancer cells. As a cell-specific sphingolipid, its function in lung cancer cells is unknown. Here we showed that SPC treatment triggered necrosis and autophagy but inhibited apoptosis in two non-small cell lung cancer cell lines: A549 cell line and H157 cell line. Then 3-methyladenine (3-MA), an autophagy inhibitor, was introduced to clarify the relationships between autophagy and necrosis or apoptosis. 3MA suppressed the survival furtherly by promoting apoptosis while had no influence on necrosis. Subsequent studies revealed that activity of AKT and mammalian target of rapamycin (mTOR) complex 1 (mTORC1) were downregulated during autophagy. Furthermore, SPC failed to promote autophagy in p53 deleted cells. Thus SPC induced autophagy in non-small cell lung cancer cells was through AKT/mTORC1 and P53 signal pathway. Besides, SPC reduced both the mitochondria membrane potential and ROS level in A549 cells. These findings provided a molecular basis of SPC-stimulated A549 cell death and support the notion that inhibition of autophagy is likely a novel anticancer mechanism.
Epithelial cells possess apical?basal polarity and loss of epithelial cell polarity contributes to tumorigenesis and cancer progression. The Crumbs (CRB) polarity protein plays a crucial role in epithelial polarity maintenance, apical membrane formation, and tissue morphogenesis. Although evidence is increasing on involvement of deregulated polarity proteins in cancers, little is currently known about the roles of the CRB (Drosophila), especially the roles of CRB3, a homolog of the CRB, in clear cell renal cell carcinoma (ccRCC). Studies have shown that CRB3 may act as a tumor suppressor in non?human mammalian cells; the study here was aimed to examine the expression status of CRB3 in ccRCC and the relationships between CRB3 expression and clinicopathologic parameters of ccRCC patients. Our results showed that CRB3 was weakly expressed in ccRCC tissues, but strongly expressed in adjacent normal kidney tissues. Patients with loss of CRB3 expression showed a significantly shorter overall survival (OS) than patients with positive CRB3 expression. Our results suggested that CRB3 may be an independent favorable prognostic factor for patients with ccRCC. We also found that overexpression of CRB3 restrained invasion and migration of 786?O cells and loss of CRB3 expression promoted invasion and migration of human embryonic kidney 293T (HEK 293T) cells. This finding may explain why the negative CRB3 expression was associated with poor prognosis in human ccRCC. Altogether, our data demonstrated that CRB3 may be used as a new independent favorable prognostic factor for human ccRCC.
BackgroundLKB1, also known as STK11, is a master kinase that serves as an energy metabolic sensor and is involved in cell polarity regulation. Recent studies have indicated that LKB1 is related to breast tumorigenesis and breast cancer progression. However, little work has been done on the roles of LKB1 in cell polarity and epithelial-mesenchymal transition in breast cancer. In this study, we tried to prove that loss of LKB1 disrupts breast epithelial cell polarity and causes tumor metastasis and invasion.MethodsThe relationships of LKB1 expression to clinic-pathological parameters and epithelial markers E-cadherin and high-molecular-weight -cytokeratin (HMW-CK) were investigated in 80 clinical breast cancer tissue samples and their paired normal control breast tissue samples by using immunohistochemistry. Then, the LKB1 expressions in metastatic and non-metastatic breast cancer cell lines were compared. The roles of LKB1 in cell polarity and epithelial-mesenchymal transition in breast cancer were determined by using immunofluorescence, western blot assay, and cell migration and invasive assays. Finally, the non-transformed human breast cell line MCF-10A was cultured in three dimensions to further reveal the role of LKB1 in breast epithelial cell polarity maintenance.ResultsHistopathological analysis showed that LKB1 expression level was significantly negatively correlated with breast cancer TNM stage, and positively correlated with ER/PR status and expression levels of E-cadherin and HMW-CK. Immunofluorescence staining showed that LKB1 was co-localized with E-cadherin at adheren junctions. In vitro analysis revealed that loss of LKB1 expression enhanced migration, invasion and the acquisition of mesenchymal phenotype, while LKB1 overexpression in MDA-MB-435 s cells, which have a low basal level of LKB1 expression, promoted the acquisition of epithelial phenotype. Finally, it was found for the first time that endogenous LKB1 knockdown resulted in abnormal cell polarity in acini formed by non-transformed breast epithelial cells grown in 3D culture.ConclusionOur data indicated that low expression of LKB1 was significantly associated with established markers of unfavorable breast cancer prognosis, such as loss of ER/PR, E-cadherin and HMW-CK. Knockdown of endogenous LKB1 gave rise to dysregulation of cell polarity and invasive phenotype of breast cancer cells.
The geometric shape of the mitral regurgitation (MR) proximal isovelocity surface area (PISA) is conventionally assumed to be a hemisphere (HS). However, in functional MR, PISA is frequently neither an HS nor a hemiellipse (HE) but is often asymmetric and crescent shaped. We used 3-dimensional transesophageal echocardiographic (3D TEE), full-volume data sets to directly measure the PISA and subsequently compared calculated values of effective regurgitant orifice area (EROA) with conventional 2D TEE techniques. EROA calculations from all PISA measurements were finally compared with the cross-sectional area at the vena contracta, a well-validated reference measure of the functional MR orifice area.
Lycopene ?-cyclase (?-LCY) is a key enzyme that catalyzes the synthesis of ?-branch carotenoids through the cyclization of lycopene. Two cDNA molecules encoding ?-LCY (designated Nt?-LCY1 and Nt?-LCY2) were cloned from Nicotiana tabacum. Nt?-LCY1 and Nt?-LCY2 are encoded by two distinct genes with different evolutionary origins, one originating from the tobacco progenitor, Nicotiana sylvestris, and the other originating from Nicotiana tomentosiformis. The two coding regions are 97% identical at the nucleotide level and 95% identical at the amino acid level. Transcripts of Nt?-LCY were detectable in both vegetative and reproductive organs, with a relatively higher level of expression in leaves than in other tissues. Subcellular localization experiments using an Nt?-LCY1-GFP fusion protein demonstrated that mature Nt?-LCY1 protein is localized within the chloroplast in Bright Yellow 2 suspension cells. Under low-temperature and low-irradiation stress, Nt?-LCY transcript levels substantially increased relative to control plants. Tobacco rattle virus (TRV)-mediated silencing of ?-LCY in Nicotiana benthamiana resulted in an increase of ?-branch carotenoids and a reduction in the levels of ?-branch carotenoids. Meanwhile, transcripts of related genes in the carotenoid biosynthetic pathway observably increased, with the exception of ?-OHase in the TRV-?-lcy line. Suppression of ?-LCY expression was also found to alleviate photoinhibition of Potosystem II in virus-induced gene silencing (VIGS) plants under low-temperature and low-irradiation stress. Our results provide insight into the regulatory role of ?-LCY in plant carotenoid biosynthesis and suggest a role for ?-LCY in positively modulating low temperature stress responses.
Bacillus anthracis, Brucella spp., and Yersinia pestis are zoonotic pathogens and biowarfare- or bioterrorism-associated agents that must be detected rapidly on-site from various samples (e.g., viscera and powders). An up-converting phosphor technology-based lateral flow (UPT-LF) strip was developed as a point-of-care testing (POCT) to satisfy the requirements of first-level emergency response. We developed UPT-LF POCT to quantitatively detect the three pathogens within 15 min. Sample and operation-error tolerances of the assay were comprehensively evaluated. The sensitivity of UPT-LF assay to bacterial detection reached 10(4) cfu · mL(-1) (100 cfu/test), with a linear quantitative range of 4 to 6 orders of magnitude. Results revealed that the UPT-LF assay exhibited a high specificity with the absence of false-positive results even at 10(9) cfu · mL(-1) of non-specific bacterial contamination. The assay could tolerate samples with a wide pH range (2 to 12), high ion strengths (? 4 mol · L(-1) of NaCl), high viscosities (? 25 mg · mL(-1) of PEG20000 or ? 20% of glycerol), and high concentrations of bio-macromolecule (? 200 mg · mL(-1) of bovine serum albumin or ? 80 mg · mL(-1) of casein). The influence of various types of powders and viscera (fresh and decomposed) on the performance of UPT-LF assay was determined. The operational error of liquid measurement exhibited few effects on sensitivity and specificity. The developed UPT-LF POCT assay is applicable under field conditions with excellent tolerance to sample complexity and operational error.
Well-ordered Cu-doped and undoped SnO2 porous thin films with large specific surface areas have been fabricated on a desired substrate using a self-assembled soft template combined with simple physical cosputtering deposition. The Cu-doped SnO2 porous film gas sensor shows a significant enhancement in its sensing performance, including a high sensitivity, selectivity, and a fast response and recovery time. The sensitivity of the Cu-doped SnO2 porous sensor is 1 order of magnitude higher than that of the undoped SnO2 sensor, with average response and recovery times to 100 ppm of H2S of ? 10.1 and ? 42.4 s, respectively, at the optimal operating temperature of 180 °C. The well-defined porous sensors fabricated by the method also exhibit high reproducibility because of the accurately controlled fabrication process. The facile process can be easily extended to the fabrication of other semiconductor oxide gas sensors with easy doping and multilayer porous nanostructure for practical sensing applications.
Ultrathin core-sheath fibers with small unilamellar vesicles (SUVs) in the core were prepared by coaxial electrospinning. SUVs/sodium hyaluranate (HA-Na)/water and polyvinylpyrrolidone (PVP)/ethanol solutions were used as core and sheath fluid in electrospinning, respectively. The ultrathin fibers were characterized by scanning and transmission electron microscopy (SEM and TEM) and laser scanning confocal microscopy (LSCM). The SUVs were successfully encapsulated in the core HA-Na matrix of the ultrathin fibers and are in the elliptic shape. The SUVs encapsulated in the core matrix of the ultrathin fibers have an excellent stability. The SUVs embedded in the ultrathin fibers are stable. When the ultrathin fibers were re-dissolved in water after one-month storage at room temperature, the rehydrated SUVs have the similar size and size distribution as the as-prepared SUVs. The liposome-loaded ultrathin fiber mats have the promising applications in wound healing materials.
We investigated the influence of typographical errors (typos) on eye movements and word recognition in Chinese reading. Participants' eye movements were tracked as they read sentences in which the target words were presented (1) normally, (2) with the initial stroke of the first characters removed (the omitted stroke condition) or (3) the first characters replaced by anomalous characters (the anomalous character condition). The results indicated that anomalous characters caused longer fixation durations and shorter outgoing forward saccade lengths than the correct words. This finding is consistent with the prediction of the theory of the processing-based strategy. Additionally, anomalous characters strongly disrupted lexical processing and whole sentence comprehension, but small stroke omissions did not. Implications of the effect of processing difficulty on forward saccade targeting for models of eye movement control during Chinese reading are discussed.
Abstract In this study, the complete mitochondrial genome of Abbottina rivularis was determined; the phylogenetic analysis with other individuals and closely related species of the gudgeons was carried out. The complete mitogenome of A. rivularis was 16,597?bp in length, which consists of 22 tRNA genes, 13 protein-coding genes, 2 rRNA genes, and 2 non-coding regions: (D-loop and OL). The overall nucleotide composition of the A. rivularis mitogenome was A: 29.92%, T: 25.75%, G: 17.15% and C: 27.18%, respectively, with an A?+?T rich feature (57.1%). This study provides useful data to genetics, conservation and evolution study of the gudgeons.
Graphene is a promising candidate material for high-speed and ultra-broadband photodetectors. However, graphene-based photodetectors suffer from low photoreponsivity and Ilight /Idark ratios due to their negligible-gap nature and small optical absorption. Here, a new type of graphene/InAs nanowire (NW) vertically stacked heterojunction infrared photodetector is reported, with a large photoresponsivity of 0.5 AW(-1) and Ilight /Idark ratio of 5 × 10(2) , while the photoresponsivity and Ilight /Idark ratio of graphene infrared photodetectors are 0.1 mAW(-1) and 1, respectively. The Fermi level (EF ) of graphene can be widely tuned by the gate voltage owing to its 2D nature. As a result, the back-gated bias can modulate the Schottky barrier (SB) height at the interface between graphene and InAs NWs. Simulations further demonstrate the rectification behavior of graphene/InAs NW heterojunctions and the tunable SB controls charge transport across the vertically stacked heterostructure. The results address key challenges for graphene-based infrared detectors, and are promising for the development of graphene electronic and optoelectronic applications.
In Chinese reading, there are no spaces to mark the word boundaries, so Chinese readers cannot target their saccades to the center of a word. In this study, we investigated how Chinese readers decide where to move their eyes during reading. To do so, we introduced a variant of the boundary paradigm in which only the target stimulus remained on the screen, displayed at the saccade landing site, after the participant's eyes crossed an invisible boundary. We found that when the saccade target was a word, reaction times in a lexical decision task were shorter when the saccade landing position was closer to the end of that word. These results are consistent with the predictions of a processing-based strategy to determine where to move the eyes. Specifically, this hypothesis assumes that Chinese readers estimate how much information is processed in parafoveal vision and saccade to a location that will carry novel information.
Retinoic acid-inducible gene I (RIG-I) is an intracellular RNA virus sensor that induces type I interferon-mediated host-protective innate immunity against viral infection. Although cylindromatosis (CYLD) has been shown to negatively regulate innate antiviral response by removing K-63-linked polyubiquitin from RIG-I, the regulation of its expression and the underlying regulatory mechanisms are still incompletely understood. Here we show that RIG-I activity is regulated by inhibition of CYLD expression mediated by the microRNA miR-526a. We found that viral infection specifically upregulates miR-526a expression in macrophages via interferon regulatory factor (IRF)-dependent mechanisms. In turn, miR-526a positively regulates virus-triggered type I interferon (IFN-I) production, thus suppressing viral replication, the underlying mechanism of which is the enhancement of RIG-I K63-linked ubiquitination by miR-526a via suppression of the expression of CYLD. Remarkably, virus-induced miR-526a upregulation and CYLD downregulation are blocked by enterovirus 71 (EV71) 3C protein, while ectopic miR-526a expression inhibits the replication of EV71 virus. The collective results of this study suggest a novel mechanism of the regulation of RIG-I activity during RNA virus infection by miR-526a and suggest a novel mechanism for the evasion of the innate immune response controlled by EV71.
The aim of this study was to enable measurement of cartilage formation by a novel biomarker of type II collagen formation. The competitive enzyme-linked immunosorbent assay (ELISA) Pro-C2 was developed and characterized for assessment of the beta splice variant of type II procollagen (PIIBNP). This is expected to originate primarily from remodeling of hyaline cartilage. A mouse monoclonal antibody (Mab) was raised in mouse, targeting specifically PIIBNP (QDVRQPG) and used in development of the assay. The specificity, sensitivity, 4-parameter fit and stability of the assay were tested. Levels of PIIBNP were quantified in human serum (0.6-2.2 nM), human amniotic fluid (163-188 nM) and sera from different animal species, e.g., fetal bovine serum (851-901 nM) with general good linearity (100% (SD 7.6) recovery) and good intra- and inter-assay variation (CV% < 10). Dose (0.1 to 100 ng/mL) and time (7, 14 and 21 days) dependent release of PIIBNP were evaluated in the conditioned medium from bovine cartilage explants (BEX) and human cartilage explants (HEX) upon stimulation with insulin-like growth factor (IGF-1), transforming growth factor (TGF)-?1 and fibroblastic growth factor-2 (FGF-2). TGF-?1 and IGF-1 in concentrations of 10-100 ng/mL significantly (p < 0.05) induced release of PIIBNP in BEX compared to conditions without treatment (WO). In HEX, IGF-1 100 ng/mL was able to induce a significant increase of PIIBNP after one week compared to WO. FGF-2 did not induce a PIIBNP release in our models. To our knowledge this is the first assay, which is able to specifically evaluate PIIBNP excretion. The Pro-C2 assay seems to provide a promising and novel marker of type II collagen formation.
Ricin, a large, water soluble toxic glycoprotein, is distributed majorly in the kernels of castor beans (the seeds of Ricinus communis L.) and has been used in traditional Chinese medicine (TCM) or other folk remedies throughout the world. The toxicity of crude ricin (CR) from castor bean kernels was investigated for the first time using an NMR-based metabolomic approach complemented with histopathological inspection and clinical chemistry. The chronic administration of CR could cause kidney and lung impairment, spleen and thymus dysfunction and diminished nutrient intake in rats. An orthogonal signal correction partial least-squares discriminant analysis (OSC-PLSDA) of metabolomic profiles of rat biofluids highlighted a number of metabolic disturbances induced by CR. Long-term CR treatment produced perturbations on energy metabolism, nitrogen metabolism, amino acid metabolism and kynurenine pathway, and evoked oxidative stress. These findings could explain well the CR induced nephrotoxicity and pulmonary toxicity, and provided several potential biomarkers for diagnostics of these toxicities. Such a (1)H NMR based metabolomics approach showed its ability to give a systematic and holistic view of the response of an organism to drugs and is suitable for dynamic studies on the toxicological effects of TCM.
Periodic segregation behaviors in fine mixtures of copper and alumina particles, including both percolation and eruption stages, are experimentally investigated by varying the ambient air pressure and vibrational acceleration. For the cases with moderate air pressure, the heaping profile of the granular bed keeps symmetrical in the whole periodic segregation. The symmetrical shape of the upper surface of the granular bed in the eruption stage, which resembles a miniature volcanic eruption, could be described by the Mogi model that illuminates the genuine volcanic eruption in the geography. When the air pressure increases, an asymmetrical heaping profile is observed in the eruption stage of periodic segregation. With using the image processing technique, we estimate a relative height difference between the copper and the alumina particles as the order parameter to quantitatively characterize the evolution of periodic segregation. Both eruption and percolation time, extracted from the order parameter, are plotted as a function of the vibration strength. Finally, we briefly discuss the air effect on the granular segregation behaviors.
Abstract Sarcocheilichthys sinensis sinensis (Bleeker, 1871), is a small benthopelagic freshwater species with high nutritional and ornamental value. In this study, the complete mitochondrial genome of S. sinensis sinensis was determined; the phylogenetic analysis with another individual and closely related species of Sarcocheilichthys fishes was carried out. The complete mitogenome of S. sinensis sinensis was 16683?bp in length, consist of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 2 non-coding regions: (D-loop and OL). It indicated that D-loop, ND2, and CytB may be appropriate molecular markers for studying population genetics and conservation biology of Sarcocheilichthys fishes.
BackgroundIndian hedgehog (Ihh) signaling pathway is known to play key roles in various aspects of normal endochondral bone development. This study tested the potential roles of high Ihh signaling in the context of injury-induced bone regeneration.MethodsA rabbit tibia defect model was established to test the effects of the implant of Ihh/mesenchymal stem cells (MSCs)/scaffold complex. Computed tomography (CT), gross observation, and standard histological and immunohistological techniques were used to evaluate the effectiveness of the treatment. In vitro studies with MSCs and C3H10T1/2 cells were also employed to further understand the cellular and molecular mechanisms.ResultsWe found that the implanted Ihh/MSCs/scaffold complex promoted bone repair. Consistently, in vitro study found that Ihh induced the upregulation of chondrocytic, osteogenic, or vascular cell markers, both in C3H10T1/2 cells and MSCs.ConclusionsOur study has demonstrated that high Ihh signaling in a complex with MSCs enhanced bone regeneration effectively in a clinically relevant acute injury model. Even though the exact underlying mechanisms are still far from clear, our primary data suggested that enhanced chondrogenesis, osteogenesis, and angiogenesis of MSCs at least partially contribute to the process. This study not only has implications for basic research of MSCs and Ihh signaling pathway but also points to the possibility of direct application of this specific paradigm to clinical bone repair.
Here, we explored the expression of S100A4 in esophageal squamous cell cancer (ESCC) tissues and investigated its role in hypoxia-induced invasion and metastasis in ESCC cell lines EC-1 and EC-9706. Immunohistochemistry analysis demonstrated that S100A4 was overexpressed in human ESCC tissues especially in ESCC tissues with deep invasion and lymph node metastasis. Hypoxia-induced S100A4 overexpression was observed in EC-1 and EC-9706 cells, in which it was associated with invasion and metastasis. Furthermore, we used EC-1 and EC-9706 cells again to upregulate or knockdown the expression S100A4 to investigate the mechanism role of S100A4 in hypoxia-induced invasion and metastasis in ESCC cells. And the results showed that S100A4 played an important role in promoting the invasion and metastasis of EC-1 and EC-9706 cells under hypoxia. Therefore, S100A4 overexpression might be an important mechanism by which hypoxia induced invasion and metastasis, and S100A4 could also be a potential target for the treatment of ESCC.
Non-small cell lung cancer (NSCLC) is the most common lung malignancy worldwide. The metastatic potential of NSCLC cells has been shown to be associated with the tumor microenvironment, which consists of tumor cells, stroma, blood vessels, immune infiltrates and the extracellular matrix. Fibroblasts can produce numerous extracellular matrix molecules and growth factors. Gefitinib has been evaluated as a first-line treatment in selected patients, and it has shown favorable efficacy especially in NSCLC, but it is not effective for everyone.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-? (A?) deposition and neurofibrillary tangles. Dl-PHPB [potassium 2-(1-hydroxypentyl)-benzoate], has been shown to have neuroprotective effects on cerebral ischemic, vascular dementia, and A?-induced animal models by inhibiting oxidative injury, neuronal apoptosis, and glial activation. The aim of the present study was to examine the effect of dl-PHPB on learning and memory in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic AD mouse models (APP/PS1) and the mechanisms of dl-PHPB in reducing A? accumulation and ? phosphorylation. Twelve-month-old APP/PS1 mice were given 30 mg/kg dl-PHPB by oral gavage for 3 months. Dl-PHPB treatment significantly improved the spatial learning and memory deficits compared with the vehicle-treated APP/PS1 mice. In the meantime, dl-PHPB obviously reduced ? hyperphosphorylation at Ser199, Thr205, and Ser396 sites in APP/PS1 mice. This reduction was accompanied by APP phosphorylation reduction and protein kinase C activation. In addition, expression of cyclin-dependent kinase and glycogen synthase kinase 3?, the most important kinases involved in ? phosphorylation, was markedly decreased by dl-PHPB treatment. Phosphorylated protein kinase B and phosphoinositide 3-kinase levels of APP/PS1 mice were significantly reduced compared with levels in wild-type mice, and dl-PHPB reversed the reduction. The effects of dl-PHPB effecting a decrease in ? phosphorylation and kinase activation were further confirmed in neuroblastoma SK-N-SH cells overexpressing wild-type human APP695. These data raised the possibility that dl-PHPB might be a promising multitarget neuronal protective agent for the treatment of AD.
Polarimetric imaging has proved its value in medical diagnostics, bionics, remote sensing, astronomy, and in many other wide fields. Pixel-level solid monolithically integrated polarimetric imaging photo-detectors are the trend for infrared polarimetric imaging devices. For better polarimetric imaging performance the high polarization discriminating detectors are very much critical. Here we demonstrate the high infrared light polarization resolving capabilities of a quantum well (QW) detector in hybrid structure of single QW and plasmonic micro-cavity that uses QW as an active structure in the near field regime of plasmonic effect enhanced cavity, in which the photoelectric conversion in such a plasmonic micro-cavity has been realized. The detector's extinction ratio reaches 65 at the wavelength of 14.7??m, about 6 times enhanced in such a type of pixel-level polarization long wave infrared photodetectors. The enhancement mechanism is attributed to artificial plasmonic modulation on optical propagation and distribution in the plasmonic micro-cavities.
Large-scale Au nanodisk arrays on Si substrate are successfully fabricated via x-ray interference lithography and followed by electron-beam vapor deposition. The Au nanodisk arrays exhibit a significant, uniform, and reproducible surface enhancement on Raman scattering signal, which enables the detection of R6G as low as 10(-8) M with an enhancement factor of 10(6). Importantly, the Au nanodisk arrays SERS-active substrates with uniformly high sensitivity also have high reproducibility and stability. The diameters of the nanodisks and the inter-disk distance can be simply optimized to obtain high enhancement in Raman signal by varying exposure time and development time in XIL process. The electric fields of the Au nanodisks with various diameters and inter-disk distance simulated by the finite difference time domain (FDTD) techniques further confirm that the Raman signal enhancement of Au nanodisks is determined by the diameters of nanodisks and the inter-disk distance of nanodisks. The Au/Ag double-layer bimetal nanodisk arrays are also fabricated which show a significant increase in the Raman signal enhancement than that of the Au nanodisk arrays. XIL nanofabrication appears to be a feasible approach to prepare uniform and reproducible SERS-active substrates with high sensitivity for practical SERS applications.
This study investigated the Pleistocene history of a semi-aquatic bug, Microvelia douglasi douglasi Scott, 1874 (Hemiptera: Veliidae) in East Asia. We used M. douglasi douglasi as a model species to explore the effects of historical climatic fluctuations on montane semi-aquatic invertebrate species. Two hypotheses were developed using ecological niche models (ENMs). First, we hypothesized that M. douglasi douglasi persisted in suitable habitats in southern Guizhou, southern Yunnan, Hainan, Taiwan and southeast China during the LIG. After that, the populations expanded (Hypothesis 1). As the spatial prediction in the LGM was significantly larger than in the LIG, we then hypothesized that the population expanded during the LIG to LGM transition (Hypothesis 2). We tested these hypotheses using mitochondrial data (COI+COII) and nuclear data (ITS1+5.8S+ITS2). Young lineages, relatively deep splits, lineage differentiation among mountain ranges in central, south and southwest China and high genetic diversities were observed in these suitable habitats. Evidence of mismatch distributions and neutrality tests indicate that a population expansion occurred in the late Pleistocene. The Bayesian skyline plot (BSP) revealed an unusual population expansion that likely happened during the cooling transition between LIG and LGM. The results of genetic data were mostly consistent with the spatial predictions from ENM, a finding that can profoundly improve phylogeographic research. The ecological requirements of M. douglasi douglasi, together with the geographical heterogeneity and climatic fluctuations of Pleistocene in East Asia, could have shaped this unusual demographic history. Our study contributes to our knowledge of semi-aquatic bug/invertebrate responses to Pleistocene climatic fluctuations in East Asia.
B-lymphocyte activation is a common characteristic of chronic hepatitis B virus (HBV) infection. B cell-activating factor (BAFF) plays a crucial role in the development and activation of B lymphocytes. This study investigated serum BAFF levels in 232 patients with different clinical diseases of chronic HBV infection [33 chronic asymptomatic HBV carrier (ASC), 53 chronic hepatitis (CH), 72 liver cirrhosis (LC), and 74 hepatocellular carcinoma (HCC)] and 61 gender- and age-matched healthy controls. Serum BAFF levels in HBV patients were significantly elevated compared with healthy controls (P<0.001). HCC patients had significantly higher levels of serum BAFF than ASC, CH, and LC (all P<0.001). Serum levels of BAFF in LC were significantly higher than in ASC (P<0.001) and CH (P=0.002). Serum level of BAFF was an independent variable associated with the presence of HCC in comparison with other disease groups in multivariate analysis. The area under receiver-operating characteristic curve (AUC) value of BAFF levels was 0.914 for HCC versus ASC, 0.825 for HCC versus CH, and 0.607 for HCC versus LC, respectively. The AUC value of BAFF levels was 0.854 for LC versus ASC and 0.748 for LC versus CH, respectively. The AUC value of BAFF (0.888) for HCC was higher than that of alpha-fetoprotein (0.776). We first demonstrate that serum BAFF levels in chronic HBV infection are elevated, correlated with clinical diseases, and could be used as a biomarker for indicating disease mechanisms, activity, and diagnosis.
Programmed cell death-1 (PD-1) is involved in hepatitis B virus (HBV) infection and single-nucleotide polymorphism (SNP) rs10204525 in the 3'-untranslated region (3' UTR) of PD1 gene was shown to be associated with the disease course of HBV infection. This study examined the associations of PD-1 mRNA expression with the clinical and viral profiles and the genotypes of rs10204525 in HBV infection. PD-1 mRNA levels in peripheral blood nuclear cells were determined by real-time quantitative reverse transcription polymerase chain reaction (PCR). PD1 rs10204525 was genotyped by bidirectional PCR amplification of specific alleles. The results showed that patients with chronic HBV infection had significantly elevated PD-1 mRNA levels than healthy controls. Patients with chronic hepatitis and hepatocellular carcinoma had significantly higher PD-1 mRNA levels than healthy controls. HBeAg (+) patients had significantly higher PD-1 mRNA levels than HBeAg (-) patients (P<0.001). PD-1 mRNA levels were sequentially increased with the elevation of HBV DNA levels. In HBV patients, but not in healthy controls, PD-1 mRNA levels were sequentially decreased from rs10204525 genotypes AA, AG to GG and the levels in genotype AA were significantly higher than in genotype GG (P=0.039). These findings suggest that increased PD-1 expression may affect the disease course of chronic HBV infection by facilitating HBV viral replication, and this may at least partially relate to PD1 3' UTR polymorphism.
Sodium taurocholate cotransporting polypeptide (NTCP) plays an important role in the enterohepatic circulation of bile acids and hepatocyte function and was recently proposed to be a functional receptor for hepatitis B virus (HBV).
Porcine circovirus type 2 (PCV2) is the primary etiological agent of postweaning multisystemic wasting syndrome (PMWS). CD44 is a widely expressed class I transmembrane glycoprotein implicated in immunological and inflammatory responses. In previous studies, the role of CD44 in host defense against microorganism infection remains controversial. The role of CD44 in host defense against PCV2 infection has never been studied before. In this study, we investigated the role of CD44 in the development of pneumonia induced by PCV2 in mice model. Upon infection, CD44 mRNA level in lung tissue was upregulated, and we confirmed a detrimental role of CD44 in host defense against PCV2 infection. The results demonstrated that CD44 deficiency could result in decreased proinflammatory cytokine production in lung induced by PCV2 in mice, suggesting a previously unrecognized role for CD44 in the development of pneumonia response to PCV2 infection.
A rapid, sensitive and reliable high-performance liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous quantification of the five main bioactive components, calycosin, calycosin-7-O-?-d-glucoside, formononetin, astragaloside IV and schisandrin in rat plasma after oral administration of Shenqi Wuwei chewable tablets. Plasma samples were extracted using solid-phase extraction separated on a CEC18 column and detected by MS with an electrospray ionization interface in multiple-reaction monitoring mode. Calibration curves offered linear ranges of two orders of magnitude with r > 0.995. The method had a lower limit of quantitation of 0.1, 0.02, 0.1, 1 and 0.1 ng/mL for calycosin, calycosin-7-O-?-d-glucoside, formononetin, astragaloside IV and schisandrin, respectively. Intra- and inter-day precisions (relative standard deviation) for all analytes ranged from 0.97 to 7.63% and from 3.45 to 10.89%, respectively. This method was successfully applied to the pharmacokinetic study of the five compounds in rats after oral administration of Shenqi Wuwei chewable tablets.
A bamboo-derived granular activated carbon with large pores was successfully prepared by KOH activation, and used to remove perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) from aqueous solution. The granular activated carbon prepared at the KOH/C mass ratio of 4 and activation temperature of 900°C had fast and high adsorption for PFOS and PFOA. Their adsorption equilibrium was achieved within 24h, which was attributed to their fast diffusion in the micron-sized pores of activated carbon. This granular activated carbon exhibited the maximum adsorbed amount of 2.32mmol/g for PFOS and 1.15mmol/g for PFOA at pH 5.0, much higher than other granular and powdered activated carbons reported. The activated carbon prepared under the severe activation condition contained many enlarged pores, favorable for the adsorption of PFOS and PFOA. In addition, the spent activated carbon was hardly regenerated in NaOH/NaCl solution, while the regeneration efficiency was significantly enhanced in hot water and methanol/ethanol solution, indicating that hydrophobic interaction was mainly responsible for the adsorption. The regeneration percent was up to 98% using 50% ethanol solution at 45°C.
Here we report InAs nanowire (NW) near-infrared photodetectors having a detection wavelength up to ?1.5 ?m. The single InAs NW photodetectors displayed minimum hysteresis with a high Ion/Ioff ratio of 10(5). At room temperature, the Schottky-Ohmic contacted photodetectors had an external photoresponsivity of ?5.3 × 10(3) AW(-1), which is ?300% larger than that of Ohmic-Ohmic contacted detectors (?1.9 × 10(3) AW(-1)). A large enhancement in photoresponsivity (?300%) had also been achieved in metal Au-cluster-decorated InAs NW photodetectors due to the formation of Schottky junctions at the InAs/Au cluster contacts. The photocurrent decreased when the photodetectors were exposed to ambient atmosphere because of the high surface electron concentration and rich surface defect states in InAs NWs. A theoretical model based on charge transfer and energy band change is proposed to explain this observed performance. To suppress the negative effects of surface defect states and atmospheric molecules, new InAs NW photodetectors with a half-wrapped top-gate had been fabricated by using 10 nm HfO2 as the top-gate dielectric.
Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells (M-PBMNCs) has been shown to be effective in treating critical limb ischemia (CLI); however, the studies of the possible prognosis predictors after autologous M-PBMNC transplantation are inadequate. The objective of the study was to assess the possible factors affecting the results of M-PBMNC transplantation for CLI.
Chrysin (5,7-di-OH-flavone), a widely distributed natural flavonoid, has been well documented for involving in various biological activities, especially in regulation of peroxisome proliferator activated receptor ? (PPAR?) activity as a modest modulator. However, the exact molecular mechanism is still unrevealed. In the current study, for the first time, we discovered that, chrysin not only significantly attenuated inflammation in high-fat feeding mice, but also alleviated high fat diet-induced hepatic, muscular steatosis in obese mice without altering the body weight. Chrysin decreases the infiltration of macrophages into adipose tissue in obese mice. In addition, chrysin was also found to induce an anti-inflammatory M2 phenotype and decreases M1 phenotype, both in peritoneal macrophages of obese mice and cultured macrophages in vitro, and thereby, chrysin changed the M1/M2 status. Our data further showed that chrysin regulated the phenotype of macrophages through enhancing the transcriptional activation of PPAR? and the expression of its target genes. Taken together, we conclude that chrysin may serve as an effective modulator of PPAR? during the pathogenesis of inflammation, thereby our findings shed light on the potential therapeutic feature of chrysin in recovering inflammatory diseases via regulating M1/M2 status.
A 30-year-old man presented with a left undescended testis, right testicular deficiency and azoospermia. Testicular biopsy revealed an absence of spermatocytes and increased numbers of Leydig cells in the undescended testis. Additional comparative analyses were undertaken to explore Sonic Hedgehog (Shh) immunostaining in the testis of juvenile and adult mice, in the testis of the patient with cryptorchidism, and in archival testicular tissue from a patient with obstructive azoospermia and a patient with prostate cancer. Shh immunostaining was demonstrated in spermatocytes in juvenile and adult mouse testis and in the patients with obstructive azoospermia and prostate cancer, suggesting that Shh signalling is involved in normal spermatogenesis. In the patient with cryptorchidism, Shh immunostaining was localized to the Leydig cells, which suggests that Shh might be involved in the abnormal expansion of the Leydig cell population in the testis. These preliminary data on the appearance of Shh protein during normal spermatogenesis might provide the basis for further investigations to clarify the role of Shh signalling in spermatogenesis during normal and pathogenic testis development.
Macrophages, owning variable phenotypes and diverse functions, were becoming the target cells in inflammatory, infectious and autoimmune diseases. In the present study, we evaluated the effect of 5,7,3',4',5'-pentamethoxyflavanone (abbreviated as PMFA), a kind of flavonoid, on macrophage polarization, and investigated the underlying mechanism. We found that PMFA significantly inhibited M1 macrophage polarization and diminished the proinflammatory cytokines, meanwhile it greatly enhanced M2 macrophage related molecules. Moreover, PMFA facilitated the phenotype shift from M1 to M2. However, PMFA only slightly inhibited the activation of T and B cells. Further researches showed that the mechanisms can be attributed to PMFA's down-regulation on p-STAT1 and up-regulation on p-STAT6, the pivotal regulatory molecules for M1 and M2 polarization, respectively. In addition, PMFA ameliorated LPS- and cecal ligation and puncture (CLP)-induced sepsis in mice, as assessed by the raise of survival rate, descend of tissue damage and bronchoalveolar lavage fluid (BALF) cytokines. PMFA significantly decreased the expression of IL-1?, IL-6 and TNF-? and reduced the infiltration of M1 macrophages in lung. As expected, adoptive transfer of PMFA-pretreated M1 macrophages significantly increased survival rate of LPS-challenged mice compared with control mice. Taken together, the results indicate that PMFA regulates macrophage polarization via targeting the STAT1/STAT6 signals and its potential use in treatment of inflammatory disease.
Aromatase inhibitors (AIs) are widely used in the treatment of hormone?dependent breast cancer and as a result, aromatase inhibitor?associated bone loss (AIBL) has become a major concern amongst patients receiving AI treatment. Modified Shu?Gan?Liang?Xue decoction (mSGLXD), a clinical prescription, has been used for ameliorating AIBL in patients with breast cancer for decades and has achieved good clinical efficacy. However, the mechanism underlying how mSGLXD influences bone homeostasis and alleviates AIBL has remained elusive. In the present study, mSGLXD was supplemented with Rhizoma Drynariae containing phytoestrogens, and the safety of mSGLXD was evaluated. mSGLXD did not possess estrogenic activity and significantly inhibited the proliferation of estrogen receptor?positive breast cancer cell line MCF?7, which suggested that mSGLXD was safe for postmenopausal patients with breast cancer. Subsequently, the effects of mSGLXD alone or in combination with anastrozole on osteoblastic MC3T3?E1 cell proliferation and differentiation were investigated. Cell counting kit?8, reverse transcription?polymerase chain reaction and biochemical methods, such as ELISA and alizarin red S staining, were used in the present study. It was revealed that mSGLXD not only stimulated MC3T3?E1 cell proliferation, but also upregulated alkaline phosphatase and osteocalcin gene and protein expression levels. High concentrations of anastrozole (10 or 100 µmol/l) markedly inhibited MC3T3?E1 cell proliferation, but this inhibitory effect was attenuated by mSGLXD. Furthermore, mSGLXD increased MC3T3?E1 cell mineralization following ??glycerophosphate and ascorbic acid induction. Therefore, the results of the present study suggested that mSGLXD may be a promising adjuvant therapy, with high safety and efficacy, for the prevention and treatment of AIBL in patients with breast cancer who receive AI treatment.
A "turn-on" and label-free fluorescent assay for the specific, rapid, and sensitive detection of 3'???5' exonuclease III activity is reported in this study. The assay is based on the Tb(3+)-promoted G-quadruplex, which lead to the enhancement of Tb(3+) fluorescence due to the energy transfer from guanines. The proposed assay is highly simple, rapid, and cost-effective, and does not require sophisticated experimental techniques such as gel-based equipment or radioactive labels. It can be used for the rapid detection of exonuclease III activity with a detection limit of 0.8 U and a RSD (n?=?6) <5 %. Notably, no dye was covalently conjugated to the DNA strands, which offers the advantages of low-cost and being interference-free.
In this study, the influence of sediments deposited on the leaves of different mangrove species due to tidal movements on photosynthetic characteristics and chlorophyll fluorescence of the species was explored. The degree of accelerated degradation among different mangrove species was also obtained. Results show that the leaves of mangrove species have varying degrees of sediment deposition. Sediment deposition leads to photosynthetic reduction and physiological stress among Kandelia candel, Aegiceras corniculatum, and Avicennia marina in the Quanzhou Bay. Thus, the deposition of suspended sediments from tidal currents is an important environmental factor that accelerates the degradation of some mangrove species.
Determining the level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative DNA damage biomarker, is vital to the study of clinical pathogenesis and drug toxicity. The principal limitation of capillary electrophoresis (CE) with UV detection is its low sensitivity. To overcome this shortcoming, we developed a micellar electrokinetic capillary chromatography (MEKC) with solid-phase extraction (SPE) for urinary 8-OHdG analysis. The sensitivity of MEKC-UV was improved using a reasonable UV system, injection mode, and SPE. The parameters affecting MEKC and SPE were also optimized. The calibration curve was linear within the range from 1 to 500 ?g L(-1). The limits of detection and quantification were 0.27 ?g L(-1) and 0.82 ?g L(-1), respectively. Interday and intraday precision were both <5.6%. The recovery of 8-OHdG in urine ranged from 94.5% to 103.2%. This method was used to measure urinary 8-OHdG from eight normal children, eight newly diagnosed leukemic children, and eight leukemic children undergoing chemotherapy. The results show that the proposed method can be used to assess oxidative stress in patients and the side effects of chemotherapeutic drugs by measuring urinary 8-OHdG.
Periodontitis is a disease, which is associated with chronic inflammation and leads to significant destruction of periodontal tissues. Periodontal ligament cells (PDLCs) constitute the largest cell population in PDL tissues and a considerable body of evidence has demonstrated an association between oxidative stress and the progression of periodontitis. However, the effects on PDLCs exposed to hydrogen peroxide (H2O2) and the molecular mechanisms by which H2O2 affects periodontitis remain to be elucidated. In the present study, the potential cytotoxic effect of H2O2 and the antioxidative function of vitamin C (Vc) in PDLCs were investigated. The results demonstrated that H2O2 treatment decreased the viability of PDLCs. The decreased PDLC viability was primarily induced by apoptosis, which was evidenced by cleaved caspases?3, caspases?9 and poly (ADP?ribose) polymerase. Following optimal Vc addition, the proapoptotic effects of H2O2 were partially antagonized. Taken together, the present study demonstrated that H2O2 primarily induced the apoptosis of PDLCs and that these adverse effects were partially rescued following treatment with Vc. These results revealed how H2O2 promotes the progression of periodontitis and provide an improved understanding of the reversal effect of antioxidant treatment. Therefore, optimal Vc administration may provide a potentially effective technique in periodontal therapy.
Triptolide (TP) is a biologically active diterpene triepoxide from the Chinese herb Tripterygium wilfordii Hook f. Here, we identify and explore TAB1 as the binding target of TP in macrophages by using a comprehensive approach combining pull-down assays, in vitro assessments, and pharmaceutical and biological evaluation. We discover that TP inhibits TAK1 kinase activity by interfering with the formation of the TAK1-TAB1 complex, and the binding affinity of TP to TAB1 correlates highly with the inhibitory activity of TP against MAPK pathway activation in macrophages. We also find that the amino acid sequence between positions 373 and 502 of TAB1 is required for TP interaction. Our results suggest that TP could be a selective small-molecule inhibitor of the TAK1-TAB1 complex and that TAB1 could be a potential therapeutic target in inflammatory disease.
Naproxen (NAP) loaded nanofibers of different structures have been successfully prepared by electrospinning. The structures of the nanofibers are NAP and cellulose acetate (CA) mixed nanofibers (NF-1), nanofibers with NAP/CA mixed core and CA sheath (NF-2), and NAP loaded liposomes and sodium hyaluronate (HA-Na) mixed core with CA sheath (NF-3). The structure and morphology of the nanofibers were characterized and the drug release behaviors were investigated. It was found that NAP can disperse in the HA-Na or CA matrix in molecular level without formation of NAP crystals and dimers. The drug release behaviors of NF-1 and NF-2 show a non-Fickian diffusion mechanism, while the NF-3 shows a specific drug release behavior with a burst release within 8h followed by a sustained drug release for 12 days. The particular two-stage drug release behavior of NF-3 nanofibers offers the materials promising applications as wound dressing materials.
Suppressor of cytokine signaling (SOCS)-1 is involved in viral infection through regulation of both innate and adaptive immunity. The SOCS1 gene polymorphisms may affect the outcome of viral infection. The relationship between SOCS1 polymorphisms and hepatitis B virus (HBV) infection has not yet been explored. This study genotyped SOCS1 rs243327 and rs33932899 polymorphisms in 477 patients with chronic HBV infection, 93 HBV infection resolvers and 215 healthy controls. In statistical analysis, p-values less than 0.05 in multiple comparisons were corrected by Bonferroni method and presented as pc. The results showed that the allele T-containing genotypes (CT+TT) of rs243327 were higher in HBV patients than resolvers and lower in resolvers than healthy controls although the difference was not significant. The allele T of rs243327 was significantly lower in resolvers than controls (p = 0.033). The genotype GC and allele C of rs33932899 were significantly less frequent in HBV patients than controls (pc < 0.001 and p < 0.001, respectively). The haplotype T/G of rs243327/rs33932899 was significantly more frequent in HBV patients than resolvers (pc < 0.001) or controls (pc = 0.009). These data indicate that SOCS1 polymorphisms might affect the susceptibility and outcome of HBV infection.
Apoptosis of microvascular endothelial cells plays a crucial role in the progression of various lung diseases and triggers microcirculatory disorder and organ dysfunction. LPS, an outer membrane component of Gram-negative bacteria, is one of the major virulence factors for lung diseases. Recent studies have shown that the Rho/Rho kinase (ROCK) pathway plays an important role in the regulation of apoptosis, inflammatory cell migration and chemokine production in various cell types and animal models. We therefore undertake this study to investigate the inhibitory effect of fasudil, a potent and selective inhibitor of ROCK, on LPS-induced apoptosis of rat pulmonary microvascular endothelial cells (PMVECs). The results suggested that fasudil effectively prevented LPS-induced injury of rat PMVECs, as determined by MTT assay, LDH activity assay, apoptosis and western blot analysis of apoptosis-related proteins Bcl-2 and Bax. Furthermore, the mechanisms underlying the protective effect were evaluated. We found that LPS-induced MYPT-1 phosphorylation was markedly suppressed by fasudil. Moreover, fasudil pretreatment obviously inhibited the activation of JNK and p38 MAPKs induced by LPS, whereas that of ERK1/2 was not affected by fasudil. In addition, inhibiting the JNK and p38 pathways by SP600125 and SB203580 respectively attenuated the LPS-induced apoptosis and regulated the expression of apoptosis-related proteins Bcl-2 and Bax. Taken together, these results demonstrate that fasudil exerts an anti-apoptotic effect in rat PMVECs, which is mediated by the inhibition of Rho/ROCK and its downstream JNK and p38 MAPKs.
China is experiencing a rapid increase in cancer incidence in elderly patients. In order to better understand this group, a large study of patients from multiple tertiary centers in the Beijing area was designed. This study was designed to provide insight into their unique treatment preferences, including the use of traditional Chinese medicine (TCM).
Unlike in English, there are no spaces between printed words in Chinese. In this study, we explored how inserting a space before or after a word affects the processing of that word in Chinese reading. Native Chinese readers' eye movements were monitored as they read sentences with different presentation conditions. The results show that inserting a space after a word facilitates its processing, but inserting a space before a word does not show this effect and inhibits the processing of that word in some cases. Our results are consistent with the prediction of a word segmentation and recognition model in Chinese Li et al., 2009, Cognit. Psychol., 58, 525. Additionally, we found that a space guides the initial landing position on the word: the initial landing position was further away from the space that inserted into the text, whether it was before or after a word.
Steamed bread is a popular staple food in Asia with different flour quality requirements from pan bread. Little is known about how glutenin characteristics affect steamed bread quality. This work investigated how deletions of high-molecular-weight glutenin subunits (HMW-GS) influence gluten properties and Chinese steamed bread quality using 16 wheat lines grown in Texas.
Post-translational regulation plays a critical role in the control of cell growth and proliferation. The phosphorylation of peroxisome proliferator-activated receptor ? (PPAR?) is the most important post-translational modification. The function of PPAR? phosphorylation has been studied extensively in the past. However, the relationship between phosphorylated PPAR?1 and tumors remains unclear. Here we investigated the role of PPAR?1 phosphorylation in human fibrosarcoma HT1080 cell line. Using the nonphosphorylation (Ser84 to alanine, S84A) and phosphorylation (Ser84 to aspartic acid, S84D) mutant of PPAR?1, the results suggested that phosphorylation attenuated PPAR?1 transcriptional activity. Meanwhile, we demonstrated that phosphorylated PPAR?1 promoted HT1080 cell proliferation and this effect was dependent on the regulation of cell cycle arrest. The mRNA levels of cyclin-dependent kinase inhibitor (CKI) p21(Waf1/Cip1) and p27(Kip1) descended in PPAR?1(S84D) stable HT1080 cell, whereas the expression of p18(INK4C) was not changed. Moreover, compared to the PPAR?1(S84A), PPAR?1(S84D) up-regulated the expression levels of cyclin D1 and cyclin A. Finally, PPAR?1 phosphorylation reduced sensitivity to agonist rosiglitazone and increased resistance to anticancer drug 5-fluorouracil (5-FU) in HT1080 cell. Our findings establish PPAR?1 phosphorylation as a critical event in human fibrosarcoma growth. These findings raise the possibility that chemical compounds that prevent the phosphorylation of PPAR?1 could act as anticancer drugs.
Recently many genetic mutations that are associated with epilepsy have been identified. The protein NIPA2 (non-imprinted in Prader-Willi/Angelman syndrome region protein 2) is a highly selective magnesium transporter encoded by the gene NIPA2 in which we have found three mutations (p.I178F, p.N244S and p.N334_E335insD) within a population of patients with childhood absence epilepsy (CAE). In this study, immunofluorescence labeling, inductively coupled plasma-optical emission spectroscopy (ICP-OES), MTT metabolic rate detection and computational modeling were utilized to elucidate how these mutations result in CAE. We found in cultured neurons that NIPA2 (wild-type) proteins were localized to the cell periphery, whereas mutant proteins were not effectively trafficked to the cell membrane. Furthermore, we found a decrease in intracellular magnesium concentration in the neurons transfected with mutant NIPA2, but no effect on the survival of neurons. To understand how low intracellular magnesium resulted in hyperexcitability, we built and analyzed a computational model to simulate the effects of mutations. The model suggested that lower intracellular magnesium concentration enhanced synaptic N-methyl-D-aspartate receptor (NMDAR) currents. This study primarily reveals that a selective magnesium transporter NIPA2 may play a role in the pathogenesis of CAE.
The aim of this study is to identify and validate protein change in the serum from PD patients. We used serum samples from 21 PD patients and 20 age-matched normal people as control to conduct a comparative proteomic study. We performed 2-DE and analyzed the differentially expressed protein spots by LC-MS/MS. In PD group 13 spots were shown to be differentially expressed compared to control group. They were identified as 6 proteins. Among these, 3 proteins were confirmed by Western blot analysis. It showed that the frequency of fibrinogen ?-chain (FGG) appeared 70% in PD, which could not be detected in control group. The protein of inter-alpha-trypsin inhibitor heavy chain H4 (ITI-H4) was found to exist two forms in serum. The full size (120 kDa) of the protein was increased and the fragmented ITI-H4 (35 kDa) was decreased in PD group. The ratio of full size ITI-H4 to fragmented ITI-H4 in PD patients was 3.85 ± 0.29-fold higher than in control group. Furthermore, fragmented Apo A-IV (? 26 kDa) was mainly detected in control group, while it was rare to be found in PD group. Above findings might be useful for diagnosis of PD. When the expressions of FGG and 120 kDa ITI-H4 are increase, as well as ? 26 kDa Apo A-IV disappear would provide strong evidence for PD.
Soil organic carbon (SOC) plays an important role in improving soil properties and the C global cycle. Limited attention, though, has been given to assessing the spatial patterns and stocks of SOC in desert ecosystems. In this study, we quantitatively evaluated the spatial variability of SOC and its influencing factors and estimated SOC storage in a region (40 km2) of the Gobi desert. SOC exhibited a log-normal depth distribution with means of 1.6, 1.5, 1.4, and 1.4 g kg(-1) for the 0-10, 10-20, 20-30, and 30-40 cm layers, respectively, and was moderately variable according to the coefficients of variation (37-42%). Variability of SOC increased as the sampling area expanded and could be well parameterized as a power function of the sampling area. Significant correlations were detected between SOC and soil physical properties, i.e. stone, sand, silt, and clay contents and soil bulk density. The relatively coarse fractions, i.e. sand, silt, and stone contents, had the largest effects on SOC variability. Experimental semivariograms of SOC were best fitted by exponential models. Nugget-to-sill ratios indicated a strong spatial dependence for SOC concentrations at all depths in the study area. The surface layer (0-10 cm) had the largest spatial dependency compared with the other layers. The mapping revealed a decreasing trend of SOC concentrations from south to north across this region of the Gobi desert, with higher levels close to an oasis and lower levels surrounded by mountains and near the desert. SOC density to depths of 20 and 40 cm for this 40 km2 area was estimated at 0.42 and 0.68 kg C m(-2), respectively. This study provides an important contribution to understanding the role of the Gobi desert in the global carbon cycle.
A previous genomewide association study of nonobstructive azoospermia (NOA) in the Han Chinese population identified three risk loci (rs12097821, rs2477686, and rs10842262) and provided strong evidence for a genetic influence in male infertility. However, recently, a follow-up study of these single nucleotide polymorphism (SNP) loci in the Japanese population showed that none of them were significantly associated with NOA. Therefore, we conducted an association study, consisting of 550 NOA cases and 555 normal controls, to further validate whether the risk of those three SNPs still existed in an independent Han Chinese male population. The association studies did not support the association of rs12097821 and rs2477686 with NOA for both genotype and allele distributions, but rs10842262 in the SOX5 gene was significantly associated with NOA (chi square = 9.31; P = 0.0095 and chi square = 9.27; P = 0.0023, respectively). Our study provides genetic evidence for SOX5 polymorphism in NOA, contributing to predicting males at high risk of NOA in Han Chinese population. Considering genetic differences among populations, future validating studies in independent samples are suggested.
Glucokinase (GK) is a hexokinase isozyme that catalyzes the phosphorylation of glucose to glucose-6-phosphate. Glucokinase activators are being investigated as potential diabetes therapies because of their effects on hepatic glucose output and/or insulin secretion. Here, we have examined the efficacy and mechanisms of action of a novel glucokinase activator, GKA23. In vitro, GKA23 increased the affinity of rat and mouse glucokinase for glucose, and increased glucose uptake in primary rat hepatocytes. In vivo, GKA23 treatment improved glucose homeostasis in rats by enhancing beta cell insulin secretion and suppressing hepatic glucose production. Sub-chronic GKA23 treatment of mice fed a high-fat diet resulted in improved glucose homeostasis and lipid profile.
Hepatitis C virus is a major cause of chronic liver disease worldwide. Xanthohumol, a prenylated flavonoid from hops, has various biological activities including an antiviral effect. It was previously characterized as a compound that inhibits bovine viral diarrhea virus, a surrogate model of hepatitis C virus. In the present work, xanthohumol was examined for its ability to inhibit hepatitis C virus replication in a cell culture system carrying replicating hepatitis C virus RNA replicon. 0.2?% DMSO and 500 units/mL interferon-alpha treatments were set as a negative and positive control, respectively. The inhibitory effect by xanthohumol was determined by the luciferase activity of the infected Huh7.5 cell lysates and the hepatitis C virus RNA levels in the culture. Xanthohumol at 3.53?µM significantly decreased the luciferase activity compared to the negative control (p?0.01). Xanthohumol at 7.05?µM further decreased the luciferase activity compared to xanthohumol at 3.53?µM (p?=?0.015). Xanthohumol at 7.05?µM or 14.11?µM achieved an inhibitory effect similar to that of interferon-alpha 2b (p?>?0.05). Xanthohumol at 3.53?µM significantly reduced the hepatitis C virus RNA level compared to the negative control (p?=?0.001). Although the results of xanthohumol at 7.05?µM had a higher variation, xanthohumol at the 7.05?µM and 14.11?µM decreased the hepatitis C virus RNA level to that achieved by interferon-alpha (p?>?0.05). In conclusion, xanthohumol displays anti-hepatitis C virus activity in a cell culture system and may be potentially used as an alternative or complementary treatment against the hepatitis C virus.
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