This study aimed to investigate the effectiveness and safety of lower doses of mifepristone combined with misoprostol for the termination of ultra-early pregnancy. A total of 2500 women with ultra-early pregnancy (amenorrhea ? 35 days) were randomly divided into 5 groups with gradually decreased dose of oral mifepristone from 150 to 50 mg followed by 200 µg of oral misoprostol 24 hours later. The primary end point was complete abortion without surgical intervention. Secondary end points were vaginal bleeding, return of menses, and side effects. Rates of complete abortion were high in all groups. Moreover, the lower doses of mifepristone led to shorter vaginal bleeding period, the return of menses on the expected date, and fewer side effects. Lower doses of mifepristone combined with 200 µg of misoprostol are as effective and safe as higher doses of this combination for the termination of ultra-early pregnancy with lower possibility of vaginal bleeding and side effects.
To investigate whether transplantation of autologous peripheral blood CD34+ stem cells is a viable approach for treating patients with advanced cirrhosis,which is currently hindered by a shortage in liver donors.
To examine whether or not the combination of diclofenac suppository with peri-prostatic nerve block (PPNB) was effective in reducing the degree of pain experienced during transrectal ultrasound (TRUS)-guided prostate biopsy in a randomised single-blind placebo-controlled trial.
This paper is to discuss the relationship among the nutritional status of vitamin A in infant's body, antibody level of hepatitis B's surface and antibody concentration of measles IgG.2ml of infant's venous blood is collected according to the inclusion criteria in planned immunization agencies at the local hospital; the method of combining dietary record review for 24 hours and diet records of 2 days is performed on infant caregivers, so as to know the eating food and its quantity for infants in successive 72 hours. Thus we conclude that the vitamin A in serum maybe has certain relationship with maintaining effective protection level of anti - HBs antibody and measles IgG antibody.
Poor cell survival and limited functional benefits have restricted the efficacy of bone marrow mesenchymal stem cells (BMSCs) in the treatment of myocardial infarction. We showed recently that hypoxia preconditioning of BMSCs and neural progenitor cells before transplantation can enhance the survival and therapeutic properties of these cells in the ischemic brain and heart. The present investigation explores a novel strategy of preconditioning BMSCs using the Hypoxia-inducible factor 1alpha (HIF-alpha) prolyl hydroxylase inhibitor dimethyloxalylglycine (DMOG) to enhance their survival and therapeutic efficacy after transplantation into infarcted myocardium.
Gut inflammation is prevalent in chronic kidney disease (CKD) and likely contributes to systemic inflammation via disruption of the epithelial tight junction with subsequent endotoxin and bacterial translocation.
Limited treatments are available for perinatal/neonatal stroke. Induced pluripotent stem cells (iPSCs) hold therapeutic promise for stroke treatment, but the benefits of iPSC transplantation in neonates are relatively unknown. We hypothesized that transplanted iPS cell-derived neural progenitors (iPSC-NPCs) would increase regeneration after stroke. Mouse pluripotent iPSCs were differentiated into neural progenitors using a retinoic acid protocol. Differentiated neural cells were characterized by using multiple criteria and assessments. Ischemic stroke was induced in postnatal day 7 (P7) rats by occluding the right middle cerebral artery and right common carotid artery. iPSC-NPCs (400,000 in 4 µl) were transplanted into the penumbra via intracranial injection 7d after stroke. Trophic factor expression in the peri-infarct tissue was measured using Western blot analysis. Animals received daily BrdU injections and were sacrificed 21d after stroke for immunohistochemistry. The vibrissae-elicited forelimb placement test was used to evaluate functional recovery. Differentiated iPSCs expressed mature neuronal markers, functional sodium and potassium channels, and fired action potentials. Several angiogenic and neurogenic trophic factors were identified in iPSC-NPCs. Animals that received iPSC-NPC transplantation had greater expression of SDF-1? and VEGF in the peri-infarct region. iPSC-NPCs stained positive for NeuN or GFAP 14 days after transplantation. iPSC-NPC-transplanted animals showed greater numbers of BrdU/NeuN and BrdU/Collagen IV co-labeled cells in the peri-infarct area compared to stroke controls, and performed better in a sensorimotor functional test after stroke. iPSC-NPC therapy may play multiple therapeutic roles after stroke by providing trophic factors, increasing angiogenesis and neurogenesis, and providing new cells for tissue repair. Stem Cells 2014.
This study was designed to investigate the protective effect of madecassoside from Hydrocotyle sibthorpioides against cognitive impairment induced by D-galactose (D-gal) in mice. The result revealed that treatment with madecassoside significantly reversed D-gal-induced learning and memory impairments, as measured by the Morris water-maze test. Studies on the potential mechanisms of this action showed that madecassoside significantly reduced oxidative stress and suppress inflammatory responses via blocking NF-?B and ERK/p38 MAPK pathways. Moreover, madecassoside markedly attenuated the content and deposition of ?-amyloid peptide by inducing a decrease in the expression of amyloid protein precursor, ?-site amyloid cleaving enzyme-1 and cathepsin B and an increase in the levels of neprilysin and insulin-degrading enzyme. Madecassoside significantly increased the expression of synapse plasticity-related proteins in the hippocampus, such as postsynaptic density 95, long-term potentiation, N-methyl-D-aspartic acid receptors, Ca(2+)/calmodulin-dependent protein kinase II, NMDA receptor subunit 1, protein kinase C, protein kinase A, cAMP-response element binding protein, and brain-derived neurotrophic factor. In addition, madecassoside significantly increased the levels of acetylcholine but decreased cholinesterase activity. In conclusion, the protective effect of madecassoside against d-gal-induced cognitive impairment was mainly due to its ability to reduce oxidative damage, improve synaptic plasticity and restore cholinergic function. These findings suggest that madecassoside can be considered as a potential agent for preventing cognitive impairment.
As an important tool for data analysis and knowledge processing, formal concept analysis (FCA) has been applied to many fields. In this paper, we introduce a new method to find all formal concepts based on formal contexts. The amount of intents calculation is reduced by the method. And the corresponding algorithm of our approach is proposed. The main theorems and the corresponding algorithm are examined by examples, respectively. At last, several real-life databases are analyzed to demonstrate the application of the proposed approach. Experimental results show that the proposed approach is simple and effective.
Due to the restricted use and ban of brominated flame retardants, organophosphorus compounds (OPs), extensively used as flame retardants and plasticizers, are ubiquitous in various environmental compartments worldwide. The present study shows that the release of OPs from a wide variety of commercial products and wastewater discharge might be considered as primary emission sources and that high potential of long-range atmospheric transport and persistence of OPs would be responsible for their presence in various matrices on a global scale. The occurrence and environmental behaviors of OPs in diverse matrices (e.g., dust, air, water, sediment, soil and biota) are reviewed. Human exposures to OPs via dermal contact, dust ingestion, inhalation and dietary intake are comprehensively evaluated. Finally, this study identifies gaps in the existing issues and generates a future agenda for the emerging contaminants OPs.
Preclinical and clinical studies have shown therapeutic potential of mild-to-moderate hypothermia for treatments of stroke and traumatic brain injury (TBI). Physical cooling in humans, however, is usually slow, cumbersome, and necessitates sedation that prevents early application in clinical settings and causes several side effects. Our recent study showed that pharmacologically induced hypothermia (PIH) using a novel neurotensin receptor 1 (NTR1) agonist, HPI-201 (also known as ABS-201), is efficient and effective in inducing therapeutic hypothermia and protecting the brain from ischemic and hemorrhagic stroke in mice. The present investigation tested another second-generation NTR1 agonist, HPI-363, for its hypothermic and protective effect against TBI. Adult male mice were subjected to controlled cortical impact (CCI) (velocity=3?m/sec, depth=1.0?mm, contact time=150?msec) to the exposed cortex. Intraperitoneal administration of HPI-363 (0.3?mg/kg) reduced body temperature by 3-5°C within 30-60?min without triggering a shivering defensive reaction. An additional two injections sustained the hypothermic effect in conscious mice for up to 6?h. This PIH treatment was initiated 15, 60, or 120?min after the onset of TBI, and significantly reduced the contusion volume measured 3 days after TBI. HPI-363 attenuated caspase-3 activation, Bax expression, and TUNEL-positive cells in the pericontusion region. In blood-brain barrier assessments, HPI-363 ameliorated extravasation of Evans blue dye and immunoglobulin G, attenuated the MMP-9 expression, and decreased the number of microglia cells in the post-TBI brain. HPI-363 decreased the mRNA expression of tumor necrosis factor-? and interleukin-1? (IL-1?), but increased IL-6 and IL-10 levels. Compared with TBI control mice, HPI-363 treatments improved sensorimotor functional recovery after TBI. These findings suggest that the second generation NTR-1 agonists, such as HPI-363, are efficient hypothermic-inducing compounds that have a strong potential in the management of TBI.
This study aimed to analyze survival, clinical responses, compliance, and adverse effects in locally advanced head and neck cancer (LAHNC) patients treated with split-dose cisplatin-based concurrent chemoradiation therapy (SD-CCRT) or cetuximab with concurrent radiation therapy (BioRT).
This paper mainly studies attribute reduction which keeps the lattice structure in formal contexts based on the property pictorial diagram. Firstly, the property pictorial diagram of a formal context is defined. Based on such diagram, an attribute reduction approach of concept lattice is achieved. Then, through the relation between an original formal context and its complementary context, an attribute reduct of complementary context concept lattice is obtained, which is also based on the property pictorial diagram of the original formal context. Finally, attribute reducts in property oriented concept lattice and object oriented concept lattice can be acquired by the relations of attribute reduction between these two lattices and concept lattice of complementary context. In addition, a detailed illustrative example is presented.
The residual stenosis estimation of an arteriovenous shunt is a valuable for evaluating outcomes of percutaneous transluminal angioplasty (PTA) treatment and surgical revision. This paper proposes a dual-channel phonoangiography (PCG) with fractional-order features to estimate the residual of stenosis estimation of arteriovenous shunt. The auscultation technique provides a non-invasive tool to monitor the degrees of arterio- venous grafts (AVGs). Then, support methods, such as the Burg autoregressive (AR) method and self-synchronization error formulation (SSEF), are used to extract fractional-order features between the loop site (L-site) and venous anastomosis site (V-site). Using 2-dimensional patterns (non-linear mapping), a generalized regression neural network (GRNN) is designed as a non-linear estimate model to indicate the outcome of surgical revision or AVG stenosis upon routine monthly examinations. For 42 long-term follow-up patients, the results of examination show the proposed GRNN based screening model efficiently estimates residual stenosis.
The ability to recognize small organic molecules and chemical modifications of host molecules is an essential capability of the adaptive immune system, which until now was thought to be mediated mainly by B cell antigen receptors. Here we report that small molecules, such as cyanine 3 (Cy3), a synthetic fluorescent molecule, and 4-hydroxy-3-nitrophenylacetyl (NP), one of the most noted haptens, are ?? T cell antigens, recognized directly by specific ?? TCRs. Immunization with Cy3 conjugates induces a rapid Cy3-specific ?? T cell IL-17 response. These results expand the role of small molecules and chemical modifications in immunity and underscore the role of ?? T cells as unique adaptive immune cells that couple B cell-like antigen recognition capability with T cell effector function.
BackgroundConsiderable controversy exists regarding the relation between maternal caffeine intake during pregnancy and risk of low birth weight (birth weight <2,500 g). We aim to assess this association using a systematic review and dose¿response meta-analysis of prospective studies.MethodsPotential articles were identified by searching MEDLINE and SCOPUS databases through 17 July 2013. Two authors independently extracted information on study design, participant characteristics and estimates of associations. Random-effects models were used to derive the summary relative risks (RRs) and corresponding 95% confidence intervals (CIs). Dose¿response relationships were assessed using generalized least-squares trend estimation.ResultsIn our meta-analysis, we included 13 prospective studies: 9 with low birth weight as a binary outcome variable (90,747 participants and 6,303 cases) and 6 with birth weight as a continuous outcome variable (10,015 participants; 2 studies reported both types of outcomes). Compared with the reference category with no or very low caffeine intake, the RR (95% CI) of low birth weight was 1.13 (1.06 to 1.21; I 2 0.0%) for low intake (50 to 149 mg/day), 1.38 (1.18 to 1.62; I 2 31.9%) for moderate intake (150 to 349 mg/day), and 1.60 (1.24 to 2.08; I 2 65.8%) for high intake (¿350 mg/day). In the dose¿response analysis, each 100-mg/day increment in maternal caffeine intake (around one cup of coffee) was associated with 13% (RR 1.13, 1.06 to 1.21) higher risk of low birth weight. The association persisted in strata defined according to various study characteristics. Moderate (¿33 g, 95% CI ¿63 to ¿4; I 2 0.3%) and high (¿69 g, 95% CI ¿102 to ¿35; I 2 0.0%) caffeine intakes were also associated with a significantly lower birth weight as compared with the reference category.ConclusionsHigher maternal caffeine intake during pregnancy was associated with a higher risk of delivering low birth weight infants. These findings support recommendations to restrict caffeine intake during pregnancy to low levels.
This study examined the effect of genistein from Hydrocotyle sibthorpioides on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute hepatic failure. Compared to the model control, genistein treatment significantly protected against LPS/D-GalN-induced liver injury, as evidenced by the decrease in serum alanine and aspartate aminotransferases activities and the attenuation of histopathological changes. Furthermore, genistein alleviated the pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-?) and nitric oxide (NO)/inducible nitric oxide synthase (iNOS) by inhibiting nuclear factor-?B (NF- ?B) activity. Genistein attenuated the elevated level of caspases-3, while augmented the expression of Bcl-2. In addition, LPS/D-GalN induced significant increase of heme oxygenase (HO), carbon monoxide and bilirubin levels and these alterations were augmented by genistein treatment. In conclusion, the protective effect of genistein on LPS/D-GalN-induced liver damage was mainly due to its ability to block NF-?B signaling pathway for anti-inflammation response, attenuate hepatocellular apoptosis and increase HO level. These findings suggest that genistein can be considered as a potential agent for preventing acute hepatic failure.
Stem cell transplantation therapy has provided promising hope for the treatment of a variety of neurodegenerative disorders. Among challenges in developing disease-specific stem cell therapies, identification of key regulatory signals for neuronal differentiation is an essential and critical issue that remains to be resolved. Several lines of evidence suggest that JNK, also known as SAPK, is involved in neuronal differentiation and neural plasticity. It may also play a role in neurite outgrowth during neuronal development. In cultured mouse embryonic stem (ES) cells, we test the hypothesis that the JNK pathway is required for neuronal differentiation. After neural induction, the cells were plated and underwent differentiation for up to 5 days. Western blot analysis showed a dramatic increase in phosphorylated JNKs at 1-5 days after plating. The phosphorylation of JNK subsequently induced activation of STAT1 and STAT3 that lead to expressions of GAP-43, neurofilament, ?III-tubulin, and synaptophysin. NeuN-colabelled with DCX, a marker for neuroblast, was enhanced by JNK signaling. Neuronal differentiation of ES cells was attenuated by treatment with SP600125, which inhibited the JNK activation and decreased the activation of STAT1 and STAT3, and consequently suppressed the expressions of GAP-43, neurofilament, ?III-tubulin, and the secretion of VEGF. Data from immunocytochemistry indicated that the nuclear translocation of STAT3 was reduced, and neurites of ES-derived neurons were shorter after treatment with SP600125 compared with control cells. These results suggest that the JNK-STAT3 pathway is a key regulator required for early neuronal differentiation of mouse ES cells. Further investigation on expression of JNK isoforms showed that JNK-3 was significantly upregulated during the differentiation stage, while JNK-1 and JNK-2 levels decreased. Our study provided interesting information on JNK functions during ES cell neuronal differentiation.
Chronic kidney disease (CKD) is associated with arterial medial calcification which plays a major role in the pathogenesis of cardiovascular disease in this population. Several factors are known to promote soft tissue and accelerated arterial calcification in CKD including systemic inflammation, altered calcium and phosphate homeostasis, hypertension, and deficiency of endogenous calcification inhibitors. The ABCC6 transporter (ATP-binding cassette subfamily C number 6), also known as multidrug resistance-associated protein 6 (MRP6), is highly expressed in the liver and kidney. Mutation of ABCC6 results in pseudoxanthoma elasticum, an inherited disorder characterized by arterial and soft tissue calcification. Given the prevalence of arterial medial calcification in CKD, the present study was undertaken to test the hypothesis that CKD may lead to acquired ABCC6 deficiency.
CCCTC-binding factor (CTCF), a highly conserved zinc finger protein, is a master organizer of genome spatial organization and has multiple functions in gene regulation. Mounting evidence indicates that CTCF regulates the imprinted genes Igf2 and H19 by organizing chromatin at the Igf2/H19 locus, although the mechanism by which CTCF carries out this function is not fully understood. By yeast two-hybrid screening, we identified vigilin, a multi-KH-domain protein, as a new partner of CTCF. Subsequent coimmunoprecipitation and glutathione S-transferase pulldown experiments confirmed that vigilin interacts with CTCF. Moreover, vigilin is present at several known CTCF target sites, such as the promoter regions of c-myc and BRCA1, the locus control region of ?-globin, and several regions within the Igf2/H19 locus. In vivo depletion of vigilin did not affect CTCF binding; however, knockdown of CTCF reduced vigilin binding to the H19 imprinting control region. Furthermore, ectopic expression of vigilin significantly downregulated Igf2 and upregulated H19, whereas depletion of vigilin upregulated Igf2 and downregulated H19, in HepG2, CNE1 and HeLa cells. These results reveal the functional relevance of vigilin and CTCF, and show that the CTCF-vigilin complex contributes to regulation of Igf2/H19.
We have demonstrated adaptive correction of specimen-induced aberration during in vivo imaging of mouse bone marrow vasculature with confocal fluorescence microscopy. Adaptive optics system was completed with wavefront sensorless correction scheme based on stochastic parallel gradient descent algorithm. Using image sharpness as the optimization metric, aberration correction was performed based upon Zernike polynomial modes. The experimental results revealed the improved signal and resolution leading to a substantially enhanced image contrast with aberration correction. The image quality of vessels at 38- and 75-?m depth increased three times and two times, respectively. The corrections allowed us to detect clearer bone marrow vasculature structures at greater contrast and improve the signal-to-noise ratio.
Seasonal influenza vaccination is one of the most common medical procedures and yet the extent to which it activates the immune system beyond inducing antibody production is not well understood. In the United States, the most prevalent formulations of the vaccine consist of degraded or "split" viral particles distributed without any adjuvants. Based on previous reports we sought to determine whether the split influenza vaccine activates innate immune receptors-specifically Toll-like receptors. High-dimensional proteomic profiling of human whole-blood using Cytometry by Time-of-Flight (CyTOF) was used to compare signaling pathway activation and cytokine production between the split influenza vaccine and a prototypical TLR response ex vivo. This analysis revealed that the split vaccine rapidly and potently activates multiple immune cell types but yields a proteomic signature quite distinct from TLR activation. Importantly, vaccine induced activity was dependent upon the presence of human sera indicating that a serum factor was necessary for vaccine-dependent immune activation. We found this serum factor to be human antibodies specific for influenza proteins and therefore immediate immune activation by the split vaccine is immune-complex dependent. These studies demonstrate that influenza virus "splitting" inactivates any potential adjuvants endogenous to influenza, such as RNA, but in previously exposed individuals can elicit a potent immune response by facilitating the rapid formation of immune complexes.
The transcription factor SoxE is mainly expressed in the gonad and involved in the regulation of gonad development and sex determination in animals. Here, we used the silkworm ovary-derived BmN4-SID1 cell line to survey the roles of the silkworm SoxE protein (BmSoxE) and predict its candidate binding targets. RNAi-mediated silencing of BmSoxE expression suppressed cell proliferation in BmN4-SID1 cells. A further cell cycle analysis revealed that this inhibition of cell proliferation was largely due to cell cycle arrest in G1 phase when BmSoxE expression was blocked in BmN4-SID1 cells. Genome-wide microarray expression analyses demonstrated that the expression levels of a set of genes were significantly altered following BmSoxE RNAi. More than half of these genes contained conserved binding sites for HMG box domain of the Sox proteins and were predicted to be candidate binding targets for BmSoxE. Importantly, some of the candidate targets may be associated with the effect of BmSoxE on cell proliferation. Several candidate target genes showed gonad-specific expression in silkworm larvae. Taken together, these data demonstrate that BmSoxE is required for cell proliferation in silkworm BmN4-SID1 cells and provide valuable information for further investigations of the molecular control exerted by the BmSoxE protein over cell proliferation and gonad development in the silkworm.
Tracing regional anthropogenic influences is important for assessing the magnitude of human interferences with the environment. In the present study, the utility of soil linear alkylbenzenes (LABs) as indicators of anthropogenic influences was examined, with the emphasis on the role of atmospheric transport in dissipating LABs from input sources to remote areas. The Pearl River Delta, South China, which has experienced rapid economic growth and urbanization, was selected as the study region. The concentrations of LABs (mean: 8.6 ng/g and median: 5.7 ng/g, with an outlier of 2,020 ng/g excluded) suggested that sewage contamination throughout the entire study region was generally light. The spatial variation of sewage pollution was significantly positively correlated with population density and per capita gross domestic product, with hot spots concentrated in the central PRD. Atmospheric deposition was hypothesized as an important input route for soil LABs in forestry and drinking water source areas with little impact of irrigation or direct wastewater discharge. This proposition could explain the opposite spatial patterns of LAB concentrations and values of a biodegradation index (5-C12+5-C13)/(5-C11+5-C10), where i-Cn defines a specific LAB congener with i and n indicating the position of the phenyl group and the number of carbon atoms on the alkyl chain, respectively. These findings somewhat validated LABs as tracers of regional anthropogenically derived contamination, with atmospheric transport of LABs as a viable dissipating mechanism.
Acute pulmonary embolism (APE) is a disorder involving the pulmonary circulation resulting from a blockage of the pulmonary artery. The present study aimed to investigate the effects of aspirin on the nuclear factor-?B (NF-?B) activity in a rat model of APE.
Studies in the general population have proposed links between nutrition and depression, but less is known about the perinatal period. Depletion of nutrient reserves throughout pregnancy and delayed postpartum repletion could increase the risk of perinatal depression. We examined the relationships of plasma folate and vitamin B12 concentrations during pregnancy with perinatal depression. At 26th-28th weeks of gestation, plasma folate and vitamin B12 were measured in women from the GUSTO mother-offspring cohort study in Singapore. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS) during the same period and at 3-month postpartum. EPDS scores of ?15 during pregnancy or ?13 at postpartum were indicative of probable depression. Of 709 women, 7.2% (n = 51) were identified with probable antenatal depression and 10.4% (n = 74) with probable postnatal depression. Plasma folate concentrations were significantly lower in those with probable antenatal depression than those without (mean ± SD; 27.3 ± 13.8 vs 40.4 ± 36.5 nmol/L; p = 0.011). No difference in folate concentrations was observed in those with and without probable postnatal depression. In adjusted regression models, the likelihood of probable antenatal depression decreases by 0.69 for every unit variation (increase) in folate (OR = 0.69 per SD increase in folate; 95% CI: 0.52, 0.94). Plasma vitamin B12 concentrations were not associated with perinatal depression. Lower plasma folate status during pregnancy was associated with antenatal depression, but not with postnatal depression. Replication in other studies is needed to determine the direction of causality between low folate and antenatal depression.
A compound was isolated from Centipeda minima using bioassay-guided screening. The structure of this compound was elucidated based on its spectral data, and it was identified as helenalin. The hepatoprotective effect of helenalin was evaluated using a liver fibrosis model induced by intragastric administration with alcohol within 24 weeks in rats. The results revealed that helenalin significantly prevented alcohol-induced hepatic injury and fibrogenesis, as evidenced by the decrease in serum aminotransferase, the attenuation of histopathological changes, and the inhibition of the hepatic fibrosis indicators, such as hyaluronic acid, type III precollagen, laminin, hydroxyproline and collagen ? type I. Mechanistically, studies showed that helenalin expedited ethanol metabolism by enhancing the alcohol and aldehyde dehydrogenase activities. Furthermore, helenalin alleviated lipid peroxidation, recruited the antioxidative defense system, inhibited CYP2E1 activity, and reduced the inflammatory mediators, including TGF-?1, TNF-?, IL-6 and IL-1? and myeloperoxidase, via down-regulation of NF-?B. Helenalin significantly decreased collagen deposition by reducing the profibrotic cytokines like transforming growth factor-?, platelet-derived growth factor-? and connective tissue growth factor, and promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9. In addition, helenalin inhibited HSC activation as evidenced by the down-regulation of ?-SMA and TGF-? levels. In conclusion, helenalin had a significant protective effect on chronic ethanol-induced hepatic fibrosis and may be a major bioactive ingredient of C. minima.
The high-resolution melting curve analysis (HRMA) might be a good alternative method for rapid detection of BRAF mutations. However, the accuracy of HRMA in detection of BRAF mutations has not been systematically evaluated. We performed a systematic review and meta-analysis involving 1324 samples from 14 separate studies. The overall sensitivity of HRMA was 0.99 (95% confidence interval (CI) = 0.75-0.82), and the overall specificity was very high at 0.99 (95% CI = 0.94-0.98). The values for the pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 68.01 (95% CI = 25.33-182.64), 0.06 (95% CI = 0.03-0.11), and 1263.76 (95% CI = 393.91-4064.39), respectively. The summary receiver operating characteristic curve for the same data shows an area of 1.00 and a Q* value of 0.97. The high sensitivity and specificity, simplicity, low cost, less labor or time and rapid turnaround make HRMA a good alternative method for rapid detection of BRAF mutations in the clinical practice.
CCCTC-binding factor (CTCF) has been implicated in numerous aspects of chromosome biology, and vigilin, a multi-KH-domain protein, participates in heterochromatin formation and chromosome segregation. We previously showed that CTCF interacts with vigilin. Here, we show that human vigilin, but not CTCF, colocalizes with HP1? on heterochromatic satellite 2 and ?-satellite repeats. CTCF up-regulates the transcription of satellite 2, while vigilin down-regulates it. Vigilin depletion or CTCF overexpression reduces the binding of HP1? on the satellite 2 locus. Furthermore, overexpression of CTCF resists the loading of vigilin onto the satellite 2 locus. Thus CTCF may regulate vigilin behavior and thus indirectly influence the binding of HP1? to the satellite 2 locus.
Juvenile hormone (JH) coordinates with 20-hydroxyecdysone (20E) to regulate larval growth and molting in insects. However, little is known about how this cooperative control is achieved during larval stages. Here, we induced silkworm superlarvae by applying the JH analogue (JHA) methoprene and used a microarray approach to survey the mRNA expression changes in response to JHA in the silkworm integument. We found that JHA application significantly increased the expression levels of most genes involved in basic metabolic processes and protein processing and decreased the expression of genes associated with oxidative phosphorylation in the integument. Several key genes involved in the pathways of insulin/insulin-like growth factor signaling (IIS) and 20E signaling were also upregulated after JHA application. Taken together, we suggest that JH may mediate the nutrient-dependent IIS pathway by regulating various metabolic pathways and further modulate 20E signaling.
Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells hold great promise in regenerative medicine for the treatment of neurodegenerative diseases. Current neuronal differentiation protocols however, are not optimized yet for the high scale production of neural precursors and terminally differentiated neurons. The present investigation reports a novel technique for the scalable production of highly uniformed neurospheres, neural precursors and terminal neurons from mouse ES and iPS cells using retinoic acid and a mechanical rotation procedure. We compared embryoid bodies (EB) and neurosphere morphology, yield of neural precursors and quality of neurons between rotary and static suspension cultures of mouse ES and iPS cells undergoing neural differentiation. Analysis of neurospheres formed under continuous rotation showed increased neurosphere uniformity and a high yield of neural precursors after neurosphere dissociation. Neurospheres formed under rotation conditions were relatively smaller, more uniform and had less dead cells and higher proliferation compared to those formed under static conditions. Neural precursors under rotation conditions matured faster, survived better, differentiated to functional neurons that stained positively for mature neuronal markers, and fired action potentials similar to the statically cultured neurons. This report thus provides a technique for the scalable production of neurons from ES and iPS cells and we suggest that rotation culture procedure can be a routine technique for stem cell neural and neuronal differentiation.
Panitumumab is a fully human monoclonal antibody approved for the treatment of epidermal growth factor receptor (EGFR) positive colorectal cancer. Recently, panitumumab has been radiolabeled with (89) Zr and evaluated for its potential to be used as immuno-positron emission tomography (PET) probe for EGFR positive cancers. Interesting preclinical results published by several groups of researchers have prompted us to develop a robust procedure for producing clinical-grade (89) Zr-panitumumab as an immuno-PET probe to evaluate EGFR-targeted therapy. In this process, clinical-grade panitumumab is bio-conjugated with desferrioxamine chelate and subsequently radiolabeled with (89) Zr resulting in high radiochemical yield (>70%, n?=?3) and purity (>98%, n?=?3). All quality control (QC) tests were performed according to United States Pharmacopeia specifications. QC tests showed that (89) Zr-panitumumab met all specifications for human injection. Herein, we describe a step-by-step method for the facile synthesis and QC tests of (89) Zr-panitumumab for medical use. The entire process of bioconjugation, radiolabeling, and all QC tests will take about 5?h. Because the synthesis is fully manual, two rapid, in-process QC tests have been introduced to make the procedure robust and error free.
The incidence of early stage renal cell carcinoma (RCC) is increasing and observational studies have shown equivalent oncological outcomes of partial versus radical nephrectomy for stage I tumours. Population studies suggest that compared with radical nephrectomy, partial nephrectomy is associated with decreased mortality and a lower rate of postoperative decline in kidney function. However, rates of chronic kidney disease (CKD) in patients who have undergone nephrectomy might be higher than in the general population. The risks of new-onset or accelerated CKD and worsened survival after nephrectomy might be linked, as kidney insufficiency is a risk factor for cardiovascular disease and mortality. Nephron-sparing approaches have, therefore, been proposed as the standard of care for patients with type 1a tumours and as a viable option for those with type 1b tumours. However, prospective data on the incidence of de novo and accelerated CKD after cancer nephrectomy is lacking, and the only randomized trial to date was closed prematurely. Intrinsic abnormalities in non-neoplastic kidney parenchyma and comorbid conditions (including diabetes mellitus and hypertension) might increase the risks of CKD and RCC. More research is needed to better understand the risk of CKD post-nephrectomy, to develop and validate predictive scores for risk-stratification, and to optimize patient management.
Surface sediments collected along the entire continental shelf of China, including Yellow Sea, the East China Sea (ECS) inner shelf and the South China Sea (SCS), were analyzed for linear alkylbenzenes (LABs), from which regional anthropogenic influences on the marine environment were assessed. The occurrence of LABs (5.6-77 ng/g; mean: 25 ng/g; median: 20 ng/g) implied light sewage contamination in coast sediment off China. Specifically, the SCS had higher sedimentary LAB levels than Yellow Sea and the ECS inner shelf, which was mainly related to the intensity of domestic wastewater discharge and marine fishing activities. Values of L/S and C??/C?? (defined in the main text) suggested certain degradation while I/E indicated limited degradation of LABs. Also, additional input sources and congener inter-conversions may have contributed to the inconsistent results for degradation of LABs in offshore sediments. Atmospheric inputs and wastewater discharge from marine fishing vessels predominantly contributed to sedimentary LABs in Yellow Sea and the SCS, while riverine input was mainly responsible for LABs along the ECS inner shelf.
Peptaibols, mainly produced by Trichoderma, play a pivotal role in controlling plant disease caused by fungi, virus, and Gram-positive bacteria. In the current study, we evaluated the control effect of Trichokonins, antimicrobial peptaibols from Trichoderma pseudokoningii SMF2, on soft rot disease of Chinese cabbage caused by a Gram-negative bacterium Pectobacterium carotovorum subsp. carotovorum and analyzed the mechanism involved. Trichokonins treatment (0.3 mg L(-1) ) enhanced the resistance of Chinese cabbage against Pcc infection. However, Trichokonins could hardly inhibit the growth of Pcc in vitro, even at high concentration (500 mg L(-1) ). Therefore, the direct effect of Trichokonins on Pcc may not the main reason why Trichokonins could control soft rot of Chinese cabbage. Trichokonin treatment led to an obvious increase in the production of reactive oxygen species hydrogen peroxide and superoxide radical, a significant enhance of the activities of pathogenesis-related enzymes catalase, polyphenoloxidase and peroxidase, and upregulation of the expression of salicylic acid - responsive pathogenesis-related protein gene acidic PR-1a in Chinese cabbage. These results indicate that Trichokonins induce resistance in Chinese cabbage against Pcc infection through the activation of salicylic acid signaling pathway, which imply the potential of Trichoderma and peptaibols in controlling plant disease caused by Gram-negative bacteria.
Vigilin contains multiple KH domains and is an evolutionarily conserved RNA-binding protein from yeast to the human. Its reported roles in human carcinogenesis are controversial in different types of human cancers. To obtain the specific expression profiles of vigilin in human hepatocellular carcinomas (HCCs), we examined vigilin protein levels in normal human liver, liver cirrhosis, adjacent non-tumor liver and HCC tumor tissues as well as in several HCC cell lines. We discovered that vigilin expression increased progressively from the liver cirrhosis tissue to adjacent non-tumor liver tissue and then to HCC tumor cells. Vigilin protein was also overexpressed in all three HCC cell lines examined, HepG2, BEL7402 and SMMC7721, when compared with the vigilin expression level in the L-02 human embryonic hepatocyte cell line. We further investigated the impact of vigilin knockdown on HCC cell proliferation, survival, motility, tumor growth and sensitivity to chemotherapy. We found that knockdown of vigilin in the BEL7402 HCC cells significantly inhibited their proliferation, colony formation and migration, but largely enhanced the cisplatin treatment-induced growth inhibition of these cells in culture. We also found that vigilin knockdown effectively inhibited the growth of BEL7402 cell-derived xenograft tumors in nude mice by decreasing the proliferation and increasing the apoptosis of the BEL7402 HCC cells. Taken together, these results suggest that progressively upregulated vigilin may serve as a molecular risk marker for HCC development, and targeting vigilin may help to inhibit HCC cell growth, survival and migration.
Prior studies show that African-American and Hispanic dialysis patients have lower mortality risk than whites. Recent age-stratified analyses suggest this survival advantage may be limited to younger age groups, but did not concurrently compare Hispanic, African-American, and white patients, nor account for differences in nutritional and inflammatory status as potential confounders. Minorities experience inequities in kidney transplantation access, but it is unknown whether these racial/ethnic disparities differ across age groups.
Mineral and bone disorder (MBD) is common and associated with mortality in patients with chronic kidney disease (CKD) Given that disarrays in serum phosphorus (P) and parathyroid hormone (PTH) levels and their changes over time are closely interrelated, modeling mortality-predictability of their combinations may help improve CKD patient management.
The regeneration of the nervous system is achieved by the regrowth of damaged neuronal axons, the restoration of damaged nerve cells, and the generation of new neurons to replace those that have been lost. In the central nervous system, the regenerative ability is limited by various factors including damaged oligodendrocytes that are essential for neuronal axon myelination, an emerging glial scar, and secondary injury in the surrounding areas. Stem cell transplantation therapy has been shown to be a promising approach to treat neurodegenerative diseases because of the regenerative capability of the stem cells that secrete neurotrophic factors and give rise to differentiated progeny. However, some issues of stem cell transplantation, such as survival, homing, and efficiency of neural differentiation after transplantation, still need to be improved. Ion channels allow for the exchange of ions between the intra- and extracellular spaces or between the cytoplasm and organelles. These ion channels maintain the ion homeostasis in the brain and play a key role in regulating the physiological function of the nervous system and allowing the processing of neuronal signals. In seeking a potential strategy to enhance the efficacy of stem cell therapy in neurological and neurodegenerative diseases, this review briefly summarizes the roles of ion channels in cell proliferation, differentiation, migration, chemotropic axon guidance of growth cones, and axon outgrowth after injury.
The increasing levels of heavy metals in the environment generally related with the rapid industrialization and urbanization. Mercury (Hg) is a global toxin with wide concerns, and China gradually becomes the main producer, consumer, and emitter of Hg in the world. However, few historical data are available on the occurrence of Hg in Chinese urban areas. Here, we collected 35 lake surface sediment samples from 35 public parks and 1 sediment core in the Luxun Park in Shanghai, a hyper-urbanization city in China, to determine the spatial and vertical distributions of total mercury (THg) and methylmercury (MeHg) and to explore the Hg pollution history with the industrial development. Higher concentrations of Hg and MeHg and greater Hg enrichment were found in urban areas compared with suburban area with the following order: central urban core area?>?developed urban area?>?developing urban area?>?suburban area. The THg concentration in the sediment core showed an increasing trend from 1876 to 2000 and a decreasing trend from 2000 to 2012, coinciding with the process of industrialization and urbanization in Shanghai. However, THg fluxes unceasingly increased from 1876 to present probably attributed to coal consumption in the suburban area and transportation agglomeration in the central urban core area. Unlike THg, no significant variations for MeHg with time and the maximum value (0.17 ?g/kg) appeared in 1947. The methylation ratio of MeHg to THg in the sediment is pretty low, and more studies are needed to further understand the fate of Hg in the environment.
The response to epidermal growth factor receptor (EGFR)-targeted therapy in metastatic colorectal cancer (mCRC) is variable because of intra-tumor heterogeneity at the genetic level, and consequently, it is important to develop sensitive and selective assays to predict patient responses to therapy. Low-abundance BRAF V600E mutations are associated with poor response to treatment with EGFR inhibitors. We developed a method for the detection of BRAF V600E mutations in mCRC using real-time wild-type blocking PCR (WTB-PCR), in which a chimera composed of locked nucleic acids and DNA is incorporated to amplify the mutant allele at high efficiency while simultaneously inhibiting the amplification of wild-type alleles. Mixing experiments showed that this method is exquisitely sensitive, with detection of the mutated allele at a mutant/wild-type ratio of 1:10,000. To demonstrate the applicability of this approach for mCRC patients, we assessed the V600E mutations in 50 clinical cases of mCRC by real-time WTB-PCR. The percentage of patients with V600E mutation as determined by WTB-PCR (16%, 8/50) was higher than by traditional PCR (10%, 5/50), suggesting an increased sensitivity for WTB-PCR. By calculating the ?C q for real-time traditional PCR, which amplifies all BRAF alleles, versus WTB-PCR, which selectively amplifies mutant BRAF, we demonstrated that among the V600E-positive mCRC patient samples, the percentage of BRAF DNA with the V600E mutation ranged from 0.05 to 52.32%. In conclusion, WTB-PCR provides a rapid, simple, and low-cost method to detect trace amounts of mutated BRAF V600E gene.
Hazardous electric arc furnace dust containing dioxins/furans and heavy metals is blended with harbor sediment, fired at 950-1100 °C to prepare lightweight aggregates. Dust addition can lower the sintering temperature by about 100 °C, as compared to a typical industrial process. After firing at 950 °C and 1050 °C, more than 99.85% of dioxins/furans originally present in the dust have been removed and/or destructed in the mix containing a dust/sediment ratio of 50:100. The heavy metals leached from all fired mixes are far below Taiwan EPA legal limits. The particle density of the lightweight aggregates always decreases with increasing firing temperature. Greater addition of the dust results in a considerably lower particle density (mostly <2.0 g cm(-3)) fired at 1050 °C and 1100 °C. However, firing at temperatures lower than 1050 °C produces no successful bloating, leading to a denser particle density (>2.0 g cm(-3)) that is typical of bricks.
Rapid urbanization has caused potential pollution of heavy metal in Shanghai. A comprehensive pollution study of heavy metals (Cd, Cu, Pb, and Zn) in 35 lake surface sediments from city parks in the four different urbanized areas of Shanghai was conducted. Intensive human activities caused moderate enrichment of the four metals in highly urbanized areas, especially Cd with the significant enrichment in the central urban core area. However, the levels of the four metals in all the sediments were lower than the corresponding consensus-based Probable Effect Concentration, indicating adverse effects not to occur frequently. The integrated pollution assessments of multiple heavy metals also suggested low ecological risk and 15-29 percent probability of toxicity in most of sediments. The metal speciation analysis showed that Cd, Cu, Pb, and Zn were dominated by the non-residual fractions and thus they have high mobility and bioavailability, indicating significant anthropogenic sources. According to the Risk Assessment Code, Cd had the highest bioavailable fraction and represented high or very high risk, followed by Zn with medium or high risks in most of samples, while no or low risk was found for Cu and Pb at most sites because they were dominated by reducible and residual fractions. Correlation analysis showed that chemical fractions of heavy metals were prone to transform among each other if environmental conditions changed. Therefore, in view of anthropogenic inputs and speciation distribution, heavy metals with very high bioavailability at very low total levels and those with low bioavailability at very high total levels should not be ignored.
Functional positive cooperative activation of the extracellular calcium ([Ca(2+)]o)-sensing receptor (CaSR), a member of the family C G protein-coupled receptors, by [Ca(2+)]o or amino acids elicits intracellular Ca(2+) ([Ca(2+)]i) oscillations. Here, we report the central role of predicted Ca(2+)-binding site 1 within the hinge region of the extracellular domain (ECD) of CaSR and its interaction with other Ca(2+)-binding sites within the ECD in tuning functional positive homotropic cooperativity caused by changes in [Ca(2+)]o. Next, we identify an adjacent L-Phe-binding pocket that is responsible for positive heterotropic cooperativity between [Ca(2+)]o and L-Phe in eliciting CaSR-mediated [Ca(2+)]i oscillations. The heterocommunication between Ca(2+) and an amino acid globally enhances functional positive homotropic cooperative activation of CaSR in response to [Ca(2+)]o signaling by positively impacting multiple [Ca(2+)]o-binding sites within the ECD. Elucidation of the underlying mechanism provides important insights into the longstanding question of how the receptor transduces signals initiated by [Ca(2+)]o and amino acids into intracellular signaling events.
A biosensor is an analytical device used for the detection of analytes, which combines a biological component with a physicochemical detector. Recently, an increasing number of biosensors have been used in clinical research, for example, the blood glucose biosensor. This review focuses on the current state of biosensor research with respect to efficient, specific and rapid detection of hepatitis B virus (HBV). The biosensors developed based on different techniques, including optical methods (e.g., surface plasmon resonance), acoustic wave technologies (e.g., quartz crystal microbalance), electrochemistry (amperometry, voltammetry and impedance) and novel nanotechnology, are also discussed.
Increasing studies have implicated the thalamus in schizophrenia, supporting the view that this structure has an important role in this disorder. Given that extensive reciprocal connections exist between the thalamus and the cerebral cortex, it is believed that disruptions of the thalamo-cortical connections may underlie the multiplicity of schizophrenic symptoms. Therefore, assessing the relationship between the thalamus and the neocortex may provide new insights into the pathophysiology of schizophrenia. We analyzed magnetic resonance images from a sample of 101 schizophrenic patients and 101 healthy controls. By assessing the correlation between the thalamic volume and cortical thickness at each vertex on the cortical surface, a thalamo-cortical network was obtained for each group. We compared the patterns of thalamo-cortical connectivity between the two groups. Compared with healthy controls, less distributed cortical regions were identified in the thalamo-cortical network in patients with schizophrenia. Vertex-wise comparison revealed decreased thalamo-cortical connectivity in bilateral inferior frontal gyrus, the left superior temporal gyrus and the right parieto-occipital region in schizophrenia. The observed disruptions in thalamo-cortical connectivity might be the substrate underlying the wide range of schizophrenic symptoms and provide further evidence to support the notion of schizophrenia as a disorder of brain dysconnectivity.
In hemodialysis (HD) patients, serum alkaline phosphatase (ALP) and parathyroid hormone (PTH) derangements are associated with mortality, but outcome-predictability using ALP and PTH in peritoneal dialysis (PD) patients remains uncertain.
The transcription factor Broad Complex (BR-C) is an early ecdysone response gene in insects and contains two types of domains: two zinc finger domains for the activation of gene transcription and a Bric-a-brac/Tramtrack/Broad complex (BTB) domain for protein-protein interaction. Although the mechanism of zinc finger-mediated gene transcription is well studied, the partners interacting with the BTB domain of BR-C has not been elucidated until now. Here, we performed a yeast two-hybrid screen using the BTB domain of silkworm BR-C as bait and identified the receptor for activated C-kinase 1 (RACK1), a scaffolding/anchoring protein, as the novel partner capable of interacting with BR-C. The interaction between BR-C and RACK1 was further confirmed by far-western blotting and pull-down assays. Importantly, the disruption of this interaction, via RNAi against the endogenous RACK1 gene or deletion of the BTB domain, abolished the nuclear import of BR-C in BmN4 cells. In addition, RNAi against the endogenous PKC gene as well as phosphorylation-deficient mutation of the predicted PKC phosphorylation sites at either Ser373 or Thr406 in BR-C phenocopied RACK1 RNAi and altered the nuclear localization of BR-C. However, when BTB domain was deleted, phosphorylation mimics of either Ser373 or Thr406 had no effect on the nuclear import of BR-C. Moreover, mutating the PKC phosphorylation sites at Ser373 and Thr406 or deleting the BTB domain significantly decreased the transcriptional activation of a BR-C target gene. Given that RACK1 is necessary for recruiting PKC to close and phosphorylate target proteins, we suggest that the PKC-mediated phosphorylation and nuclear import of BR-C is determined by its interaction with RACK1. This novel finding will be helpful for further deciphering the mechanism underlying the role of BR-C proteins during insect development.
BRAF mutations have been well described in non-small cell lung cancer (NSCLC) for several years, but the clinical features of patients harboring BRAF mutations are still not well described. We performed a meta-analysis to identify common clinical features in NSCLC patients carrying BRAF mutations.
Genotyping of thiopurine S-methyltransferase (TPMT) is recommended for predicting the adverse drug response of thiopurines. In the current study, a novel version of allele-specific PCR (AS-PCR), termed competitive real-time fluorescent AS-PCR (CRAS-PCR) was developed to analyze the TPMT*2 genotype in ethnic Chinese. This technique simultaneously uses wild-type and mutant allele-specific scorpion primers in a single reaction. To determine the optimal conditions for both traditional AS-PCR and CRAS-PCR, we used the Taguchi method, an engineering optimization process that balances the concentrations of all components using an orthogonal array rather than a factorial array. Instead of running up to 264 experiments with the conventional factorial method, the Taguchi method achieved the same optimization using only 16 experiments. The optimized CRAS-PCR system completely avoided non-specific amplification occurring in traditional AS-PCR and could be performed at much more relaxed reaction conditions at 1% sensitivity, similar to traditional AS-PCR. TPMT*2 genotyping of 240 clinical samples was consistent with published data. In conclusion, CRAS-PCR is a novel and robust genotyping method, and the Taguchi method is an effective tool for the optimization of molecular analysis techniques.
Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. The B-type Raf proto-oncogene (BRAF) plays an important role in the mitogen-activated protein kinase (MAPK) signaling cascade during CRC. The presence of BRAFV600E mutation can determine the response of a tumor to chemotherapy. However, the association between the BRAFV600E mutation and the clinicopathological features of CRC remains controversial. We performed a systematic review and meta-analysis to estimate the effect of BRAFV600E mutation on the clinicopathological characteristics of CRC.
Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH) therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p.) was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1) positive endothelial progenitor cells (EPCs) in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ) and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke.
To introduce our experience of treating locally and regionally recurrent head and neck cancer patients with BNCT at Tsing Hua Open-Pool Reactor in Taiwan, 12 patients (M/F=10/2, median age 55.5 Y/O) were enrolled and 11 received two fractions of treatment. Fractionated BNCT at 30-day interval with adaptive planning according to changed T/N ratios was feasible, effective and safe for selected recurrent head and neck cancer in this trial.
Alkaline polymer electrolyte fuel cells (APEFCs) promise the use of nonprecious metal catalysts and thus have attracted much research attention in the recent decade. Among the challenges of developing practical APEFC technology, the chemical stability of alkaline polymer electrolytes (APEs) seems to be rather difficult. Research found that, upon attachment of a cationic functional group, an originally stable polymer backbone, such as polysulfone (PSF), would degrade in an alkaline environment. In the present work, we try to employ poly(ether ether ketone) (PEEK), a very inert engineering plastic, as the backbone of APEs. The PEEK is functionalized with both a sulfonic acid (SA) group and a quaternary ammonia (QA) group, with the latter as the majority amount. Ionic cross-linking between SA and QA has rendered the thus-obtained membrane (xQAPEEK) with high mechanical strength and low swelling degree. More importantly, the xQAPEEK membrane exhibits outstanding stability in a 1 mol/L KOH solution at 80 °C for a test period of 30 days: the total weight loss of xQAPEEK is only 6 wt %, in comparison to a large degradation of quaternary ammonia PSF (more than 40 wt %) under the same conditions. Our findings not only have demonstrated an effective approach to preparing PEEK-based APE but also cast a new light on the development of highly stable APEs for fuel-cell application.
Toxic arsenics in an AsH3 scrubber sludge were thermally stabilized in the temperature range of 973-1,373 K. To better understand how the high-temperature treatments can stabilize arsenics in the sludge, their synchrotron X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectra of arsenics were determined. It is found that the reduced arsenic leachability may be associated with the formation of As2O5 (51-59%) and embedded As(V) within the Ca3(PO4)2 matrix (41-49%) in the stabilized sludge. In addition, the As-O bond distances in the stabilized As2O5 are much less than that of normal As2O5 by 0.05-0.07 Å. The shorter As-O bond distances accompanied with the higher bonding energy also have a contribution to the thermal stabilization of arsenics.
Sediment has been recognized as a gigantic sink of organic materials and therefore can record temporal input trends. To examine the impact of anthropogenic activities on the marginal seas off China, sediment cores were collected from the Yellow Sea, the inner shelf of the East China Sea (ECS), and the South China Sea (SCS) to investigate the sources and spatial and temporal variations of organic materials, i.e., total organic carbon (TOC) and aliphatic hydrocarbons. The concentration ranges of TOC were 0.5-1.29, 0.63-0.83, and 0.33-0.85%, while those of ?n-C14-35 (sum of n-alkanes with carbon numbers of 14-35) were 0.08-1.5, 0.13-1.97, and 0.35-0.96 ?g/g dry weight in sediment cores from the Yellow Sea, ECS inner shelf, and the SCS, respectively. Terrestrial higher plants were an important source of aliphatic hydrocarbons in marine sediments off China. The spatial distribution of ?n-C14-35 concentrations and source diagnostic ratios suggested a greater load of terrestrial organic materials in the Yellow Sea than in the ECS and SCS. Temporally, TOC and ?n-C14-35 concentrations increased with time and peaked at either the surface or immediate subsurface layers. This increase was probably reflective of elevated inputs of organic materials to marginal seas off China in recent years, and attributed partly to the impacts of intensified anthropogenic activities in mainland China. Source diagnostics also suggested that aliphatic hydrocarbons were mainly derived from biogenic sources, with a minority in surface sediment layers from petroleum sources, consistent with the above-mentioned postulation.
Cell therapy is emerging as a viable therapy to restore neurological function after stroke. Many types of stem/progenitor cells from different sources have been explored for their feasibility and efficacy for the treatment of stroke. Transplanted cells not only have the potential to replace the lost circuitry, but also produce growth and trophic factors, or stimulate the release of such factors from host brain cells, thereby enhancing endogenous brain repair processes. Although stem/progenitor cells have shown a promising role in ischemic stroke in experimental studies as well as initial clinical pilot studies, cellular therapy is still at an early stage in humans. Many critical issues need to be addressed including the therapeutic time window, cell type selection, delivery route, and in vivo monitoring of their migration pattern. This review attempts to provide a comprehensive synopsis of preclinical evidence and clinical experience of various donor cell types, their restorative mechanisms, delivery routes, imaging strategies, future prospects and challenges for translating cell therapies as a neurorestorative regimen in clinical applications.
Elevated serum phosphate has emerged as a major risk factor for vascular calcification. The sodium-dependent phosphate cotransporter, PiT-1, was previously shown to be required for phosphate-induced osteogenic differentiation and calcification of cultured human vascular smooth muscle cells (VSMCs), but its importance in vascular calcification in vivo and the potential role of its homologue, PiT-2, have not been determined. We investigated the in vivo requirement for PiT-1 in vascular calcification using a mouse model of chronic kidney disease and the potential compensatory role of PiT-2 using in vitro knockdown and overexpression strategies.
Stem cell transplantation therapy has emerged as a promising regenerative medicine for ischemic stroke and other neurodegenerative disorders. However, many issues and problems remain to be resolved before successful clinical applications of the cell-based therapy. To this end, some recent investigations have sought to benefit from well-known mechanisms of ischemic/hypoxic preconditioning. Ischemic/hypoxic preconditioning activates endogenous defense mechanisms that show marked protective effects against multiple insults found in ischemic stroke and other acute attacks. As in many other cell types, a sub-lethal hypoxic exposure significantly increases the tolerance and regenerative properties of stem cells and progenitor cells. So far, a variety of preconditioning triggers have been tested on different stem cells and progenitor cells. Preconditioned stem cells and progenitors generally show much better cell survival, increased neuronal differentiation, enhanced paracrine effects leading to increased trophic support, and improved homing to the lesion site. Transplantation of preconditioned cells helps to suppress inflammatory factors and immune responses, and promote functional recovery. Although the preconditioning strategy in stem cell therapy is still an emerging research area, accumulating information from reports over the last few years already indicates it as an attractive, if not essential, prerequisite for transplanted cells. It is expected that stem cell preconditioning and its clinical applications will attract more attention in both the basic research field of preconditioning as well as in the field of stem cell translational research. This review summarizes the most important findings in this active research area, covering the preconditioning triggers, potential mechanisms, mediators, and functional benefits for stem cell transplant therapy.
Mixtures consisting of harbor sediment and slag waste from steel industry containing toxic components are fired to produce non-hazardous construction materials. The fired pellets become lighter as firing temperature increases. At a sintering temperature of ?1050°C, the fired pellets are in a form of brick-like product, while at 1100°C, they become lightweight aggregates. Calcium silicate, kyanite, and cristobalite are newly formed in the pellets after firing, demonstrating that calcium oxide acts as a flux component and chemically reacted with Si- and/or Al-containing components to promote sintering. Dioxin/furan content present in the pure slag is 0.003ng I-TEQg(-1) and, for the fired pellet consisting of slag and sediment, the content appears to be destructed and diminishes to 0.0003ng I-TEQg(-1) after 950°C-firing; while it is 0.002ng I-TEQg(-1) after firing at 1100°C, suggesting that dioxins/furans in the 950°C-fired pellets have a greater chance to escape to atmosphere due to a slower sintering reaction and/or that construction of dioxins/furans from molten chloride salts co-exists with their destruction. Multiple toxicity characteristic leaching procedure extracts Cu, Cr, Zn, Se, Cd, Pb, Ba, As, and Hg from all fired products at negligible levels.
Abnormalities in serum alkaline phosphatase (ALP) and intact parathyroid hormone (PTH) concentrations, as biochemical markers of bone turnover in dialysis patients, correlate with increased mortality in maintenance hemodialysis (MHD) patients. Changes in bone turnover rate vary with age. The mortality predictability of serum ALP and PTH levels in MHD patients may be different across ages.
The implantable stimulator for epileptic seizure suppression with loading impedance adaptability was proposed in this work. The stimulator consisted of the high voltage generator, output driver, adaptor, and switches, can constantly provide the required 40-?A stimulus currents, as the loading impedance varied within 10 k? -300 k?. The performances of this design have been successfully verified in silicon chip fabricated by a 0.35- ?m 3.3-V/24-V CMOS process. The power consumption of this work was only 1.1 mW-1.4 mW. The animal test results with the fabricated chip of proposed design have successfully verified in the Long-Evans rats with epileptic seizures.
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