The purpose of this study is to predict human jejunal permeability (P(eff)) and fraction absorbed in human (%F(a)) for a group of antibacterial fluoroquinolones (FQs), by using a biophysical model based on measured Caco-2 permeability. The predicted P(eff) (in 10(-4) cm · s(-1) units) ranged from 0.7 (norfloxacin) to 4.5 (pefloxacin). The calculated %F(a) for norfloxacin = 51% (lit. 35%) and for ciprofloxacin = 76% (lit. 81%). Most of the FQs showed calculated %F(a)>90%, and are expected to be well-absorbed. Estimates of P(eff) can be predicted by the biophysical model. From these values, the human absorption may be calculated. Where absorption comparisons were possible, the agreement was acceptably good.
The objective of this study is to evaluate whether the accumulation model developed by Zarfl et al. (2008) could be used to predict the minimal inhibitory concentration (MIC) of a group of antibacterial fluoroquinolones (FQs) for Escherichia coli (E. coli). Our model, which is based on the "Fick-Nernst-Planck" equation and the permeability of the neutral and charged species as well as the physicochemical parameters of the FQs, could predict 1/MIC90 using a linear function. It is envisaged that in the drug development projects of new FQs, the accumulation model described in this study could be utilized as an effective tool to enable early assessment of MIC value using physiochemical parameters.
Schizophrenia is a prevalent psychiatric disorder with a complex etiology. Mitochondrial dysfunction has been frequently reported in schizophrenia. Phosphatase and tension homologue-induced kinase 1 (PINK1) and presenilin-associated rhomboid-like protease (PARL) are mitochondrial proteins, and genetic variants of these two genes may confer genetic susceptibility to schizophrenia by influencing mitochondrial function. In this study, we conducted a two-stage genetic association study to test this hypothesis. We genotyped 4 PINK1 and 5 PARL genetic variants and evaluated the potential association of the 9 SNPs with schizophrenia in two independent case-control cohorts of 2510 Han Chinese individuals. No positive association of common genetic variants of the PINK1 and PARL genes with schizophrenia was identified in our samples after Bonferroni correction. Re-analysis of the newly updated Psychiatric Genetics Consortium (PGC) data sets confirmed our negative result. Intriguingly, one PINK1 SNP (rs10916832), which showed a marginally significant association in only Hunan samples (P = 0.032), is associated with the expression of a schizophrenia susceptible gene KIF17 according to the expression quantitative trait locus (eQTL) analysis. Our study indicated that common genetic variants of the PINK1 and PARL genes are unlikely to be involved in schizophrenia. Further studies are essential to characterize the role of the PINK1 and PARL genes in schizophrenia.
To identify the potential risk factors associated with Shenqifuzheng injection (SFI), a solution made of Dangshen (Radix Codonopsis) and Huangqi (Radix Astragali Mongolici), for the timely provision of information to regulatory authorities.
Our understanding of Hepatitis E virus (HEV) has changed enormously over the past 30 years, from a waterborne infection causing outbreaks of acute hepatitis in developing countries to an infection of global distribution causing a range of hepatic and extra-hepatic illness. However, the key proteins playing important parts in the virus infection were still unknown. Understanding the changes of cellular proteins in these cells exposed to HEV is helpful for elucidating molecular mechanisms associated with function alterations of HEV-infected susceptible cells. In the present study, a comparative gel-based proteomic analysis was employed to study the changes in cellular proteins of A549 exposed to HEV in vitro to provide novel information for understanding the functional alterations of A549 induced by HEV infection.
The synthesis of D-isoascorbyl stearate from D-isoascorbic acid and stearic acid with immobilized lipase (Novozym(®)435) as catalyst was studied. Response surface methodology and Box-Behnken design with six variables and three levels were employed to evaluate the effects of processing conditions on the conversion of D-isoascorbic acid. The results confirmed that the response surface method and statistical analysis were proved to be useful in developing optimal conditions for D-isoascorbyl stearate synthesis. The optimum conditions were predicted as follows: reaction temperature 48 °C, reaction time 17.7 h, immobilized lipase amount 50.0 % (w/w, of D-isoascorbic acid), substrate molar ratio 9:1 (stearic acid to D-isoascorbic acid), D-isoascorbic acid concentration 0.14 mol/L (based on solvent), 4A molecular sieve addition 200 g/L (based on solvent), and the optimal conversion was 90.6 %. Through the kinetics model fitting of the esterification, it was considered that the esterification conformed to a Ping-Pong bi-bi kinetic model with D-isoascorbic acid inhibition, and the obtained kinetic constants showed that the inhibition of D-isoascorbic acid and the enzyme affinity to substrate were abate with the increase of the reaction temperature.
Abnormalities in mitochondrial complex I, which is responsible for controlling mitochondrial function, have been implicated in a variety of diseases associated with mitochondrial dysfunction, potentially including schizophrenia. The NADH dehydrogenase Fe-S protein 1 (NDUFS1) is the largest subunit of complex I. To explore whether the encoding NDUFS1 gene confers susceptibility to schizophrenia or is associated with the severity of typical symptoms of schizophrenia, we recruited 519 stable schizophrenia patients receiving clozapine treatment and 594 healthy controls for genotyping to investigate the association of four selected tagging single-nucleotide polymorphisms (SNPs) of NDUFS1 and both schizophrenia risk and symptom severity. The severity of psychotic symptoms was evaluated using the Positive and Negative Syndrome Scale and then tested for association with the four SNPs. The SNP rs1044120 showed significant association with schizophrenia (adjusted P=0.032). The frequency of the G allele of rs1044120 was significantly higher in patients than among the healthy controls (adjusted P=0.008). Stratification by sex revealed a significant association between the rs1044120 polymorphism and schizophrenia among males (adjusted P=0.036 and 0.008 in genotypic and allelic comparisons, respectively). We also observed a significant difference in the negative symptom scores among the three genotypes among these males (adjusted P=0.036). Post hoc comparisons showed that rs1044120 G/G carriers had higher negative symptom scores than those with G/T and T/T carriers (raw P=0.035 and 0.005, respectively). Our findings suggest that NDUFS1 may confer susceptibility to schizophrenia in male subjects, acting as a causative factor for the severity of negative symptoms in schizophrenia.Journal of Human Genetics advance online publication, 30 October 2014; doi:10.1038/jhg.2014.94.
A phage-displayed library of variable domain of heavy chain of the heavy chain antibody (VHH) or nanobody (Nb) was constructed after immunizing an alpaca with aflatoxin B1 (AFB1) conjugated with bovine serum albumin (AFB1-BSA). Two AFB1-specific nanobodies were selected. The obtained nanobodies were compared to an aflatoxin-specific monoclonal antibody B5 with respect to stability under organic solvents and high temperature. The two nanobodies could bind antigen specifically after exposure to temperatures as high as 95 °C. Besides, the nanobodies showed better or similar tolerance to organic solvents. A competitive ELISA with nanobody Nb26 was developed for the analysis of AFB1, exhibiting an IC50 value of 0.754 ng/mL (2.4 ?M), linear range from 0.117 to 5.676 ng/mL. Due to the high tolerance to methanol, sample extracts were analyzed by nanobody-based ELISA without dilution. The recovery from spiked peanut, rice, corn and feedstuff ranged from 80 to 115%. In conclusion, the isolated nanobodies are excellent candidates for immunoassay application in aflatoxin determination.
Despite its superiority for evaluating gene expression, real-time quantitative polymerase chain reaction (qPCR) results can be significantly biased by the use of inappropriate reference genes under different experimental conditions. Reaumuria soongorica is a dominant species of desert ecosystems in arid central Asia. Given the increasing interest in ecological engineering and potential genetic resources for arid agronomy, it is important to analyze gene function. However, systematic evaluation of stable reference genes should be performed prior to such analyses. In this study, the stabilities of 10 candidate reference genes were analyzed under 4 kinds of abiotic stresses (drought, salt, dark, and heat) within 4 accessions (HG010, HG020, XGG030, and XGG040) from 2 different habitats using 3 algorithms (geNorm, NormFinder, and BestKeeper). After validation of the ribulose-1,5-bisphosphate carboxylase/oxygenase large unite (rbcL) expression pattern, our data suggested that histone H2A (H2A) and eukaryotic initiation factor 4A-2 (EIF4A2) were the most stable reference genes, cyclophilin (CYCL) was moderate, and elongation factor 1? (EF1?) was the worst choice. This first systematic analysis for stably expressed genes will facilitate future functional analyses and deep mining of genetic resources in R. soongorica and other species of the Reaumuria genus.
Dental pulp stem cells (DPSCs) can be induced towards odontogenic differentiation. Previous studies have shown that vascular endothelial growth factor (VEGF) is able to induce the osteogenic differentiation of cells, but the effectiveness of VEGF in the odontogenic differentiation of DPSCs remains unclear. This study aimed to investigate the effects of lentivirus?mediated human VEGF gene transfection on the proliferation and odontogenic differentiation of human DPSCs in vitro. DPSCs were transfected with either lentiviral pCDH?CMV?MCS?EFI?copGFP (pCDH) vector or recombinant pCDH?VEGF vector, and the growth characteristics of the resulting DPSCs/Vector and DPSCs/VEGF were subsequently assessed. The odontogenic differentiation genes of the two groups of cells, including alkaline phosphatase, osteocalcin, dentin sialophosphoprotein and dentin matrix protein 1 (DMP1), were evaluated by quantitative polymerase chain reaction (qPCR). The specific proteins of odontogenic differentiation, including dentin sialoprotein and DMP1, were analyzed by western blotting. DPSCs/VEGF showed similar proliferation characteristics to DPSCs/Vector during the observation period. qPCR results showed that the relative VEGF gene expression was significantly higher in DPSCs/VEGF than that in DPSCs/Vector two days after transfection (P<0.01). Similarly, western blot analysis showed that the protein expression levels of VEGF were higher in DPSCs/VEGF than those in DPSCs/Vector. On the first, fourth, eighth and 16th days after lentivirus-mediated transfection, the expression of odontogenic differentiation-specific genes and proteins was higher in DPSCs/VEGF than that in DPSCs/Vector. These results indicated that lentivirus-mediated VEGF gene transfection promoted the odontogenic differentiation of human DPSCs in vitro.
BackgroundLupus nephritis (LN) is one of most common secondary glomerulonephritis. There is no ideal method to simultaneously assess renal structure and function in patients with LN. The aim of this study is to investigate the utility of diffusion weighted imaging (DWI) and blood oxygen level-dependent (BOLD) MR imaging in the assessment of renal involvement and pathological changes in patients with LN.MethodsSixty-five patients with LN and 16 healthy volunteers underwent coronal echo-planar DWI and BOLD MR imaging of the kidneys. The apparent diffusion coefficient (ADC) and R2* values of the kidneys were calculated with b values of 0 and 500 s/mm2. The relationship between the renal injury variables and the ADCs or R2* values were evaluated. And 16 of 65 patients with LN underwent a repeated evaluation after the induction treatment for 9 to 12 months.ResultsThe mean ADC values of kidneys in patients with LN were 2.40¿±¿0.25 × 10¿3 mm2/ s, the mean R2* values of the renal cortex and medulla were 11.03¿±¿1.60/sec and 14.05¿±¿3.38/sec respectively, which were all significantly lower than that in volunteers. In patients with LN, the mean ADC values were correlated with eGFR (r¿=¿0.510, p¿<¿0.01). There was a negative correlation between the mean ADC values and renal pathology chronicity indexes (r¿=¿¿0.249, p¿<¿0.05), the R2* values of the renal medulla and proteinuria (r¿=¿¿0.244, p¿<¿0.05), and the degree of tubulointerstitial lesions (r¿=¿¿0.242, p¿<¿0.05). The ADC and R2* values of kidneys were significantly higher than those of pre-treatment in complete remission patients.ConclusionsDWI and BOLD MR imaging of kidneys may be used to noninvasively monitor the disease activity and evaluate therapeutic efficacy in lupus nephritis.
The role of heat shock proteins (HSPs) in heat tolerance has been demonstrated in cultured cells and animal tissues, but rarely in whole organisms because of methodological difficulties associated with gene manipulation. By comparing HSP70 expression patterns among representative species of reptiles and birds, and by determining the effect of HSP70 overexpression on embryonic development and hatchling traits, we have identified the role of HSP70 in the heat tolerance of amniote embryos. Consistent with their thermal environment, and high incubation temperatures and heat tolerance, the embryos of birds have higher onset and maximum temperatures for induced HSP70 than do reptiles, and turtles have higher onset and maximum temperatures than do lizards. Interestingly, the trade-off between benefits and costs of HSP70 overexpression occurred between life-history stages: when turtle embryos developed at extreme high temperatures, HSP70 overexpression generated benefits by enhancing embryo heat tolerance and hatching success, but subsequently imposed costs by decreasing heat tolerance of surviving hatchlings. Taken together, the correlative and causal links between HSP70 and heat tolerance provide, to our knowledge, the first unequivocal evidence that HSP70 promotes thermal tolerance of embryos in oviparous amniotes.
The aim of this study was to investigate the effects of pinocembrin on brain ischemia/reperfusion (I/R) injury and the potential involvement of autophagy activity changes in the penumbra area in the mechanisms of pinocembrin activity. Focal cerebral I/R model was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by 24 h reperfusion. Pinocembrin was administered intravenously at different doses (1, 3, and 10 mg/kg, respectively) at the onset of reperfusion. Neurological function, brain infarction and brain swelling ratio were evaluated. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method and immunohistochemical analysis (Caspase-3) were used to evaluate apoptosis in the penumbra cortex. Two key proteins of autophagy, LC3B and Beclin1, were detected by western blot. The results showed that pinocembrin-treatment could significantly reduce neurological deficit scores, infarct volume, cerebral edema and improve pathological lesion in the I/R rats. Pinocembrin-treatment could also reduce the number of TUNEL-positive and Caspase-3-positive neurons, and upregulate the expression of LC3B and Beclin1 in penumbra area. These results suggested that pinocembrin could protect the brain against I/R injury, and the possible mechanisms might be attributed to inhibition of apoptosis and reversed autophagy activity in penumbra area.
We describe the metagenomics-derived feline enteric virome in the faeces of 25 cats from a single shelter in California. More than 90?% of the recognizable viral reads were related to mammalian viruses and the rest to bacterial viruses. Eight viral families were detected: Astroviridae, Coronaviridae, Parvoviridae, Circoviridae, Herpesviridae, Anelloviridae, Caliciviridae and Picobirnaviridae. Six previously known viruses were also identified: feline coronavirus type 1, felid herpes 1, feline calicivirus, feline norovirus, feline panleukopenia virus and picobirnavirus. Novel species of astroviruses and bocaviruses, and the first genome of a cyclovirus in a feline were characterized. The RNA-dependent RNA polymerase region from four highly divergent partial viral genomes in the order Picornavirales were sequenced. The detection of such a diverse collection of viruses shed within a single shelter suggested that such animals experience robust viral exposures. This study increases our understanding of the viral diversity in cats, facilitating future evaluation of their pathogenic and zoonotic potentials.
Streptococcus suis, an important zoonotic pathogen, is a highly diverse species with only a subset of strains that cause disease in humans. Our previous study proposed a minimum core genome (MCG) sequence typing method and defined seven MCG groups, with MCG group 1 as the prevalent group causing human infections. In this study, we identified a set of 10 single nucleotide polymorphisms (SNPs) distributed in six genes that were used to identify the seven MCG groups. The 10 SNPs were typed for 179 S. suis isolates collected from slaughtered pigs. The most prevalent groups among the tested isolates were MCG groups 6 and 7. Most of the isolates (147/179) were genotyped as mrp negative, epf negative, sly negative, and CDS2157 positive. The 179 isolates were also typed by multilocus sequence typing (MLST) and divided into 115 sequence types (STs), 111 of which were new. The 6 serotypes (29, 11, 5, 12, 30, and 2) represented 72.3% of the serotyped isolates. Our data show that the typing assay facilitates the application of genome data to the surveillance of S. suis.
Conformational B-cell epitopes play an important role in the epitope-based vaccine design. The increase of available data promotes the development of computational methods. Compared with the wet experiments, the computational methods are faster and more economic. In the past few years, a number of computational methods (especially the machine learning-based methods) have been developed to predict the conformational B-cell epitopes. In this chapter, we introduce important data resources and computational methods, which are publicly available. Moreover, we introduce our ensemble learning-based method that can predict the conformational epitopes from sequences. These promising methods may assist immunologists in identifying potential vaccine candidates.
Identification and characterization of B-cell epitopes in target antigens is one of the key steps in epitope-driven vaccine design, immunodiagnostic tests, and antibody production. For localizing epitopes by experimental methods is time consuming and cost expensive, researchers have been developing in silico or computational models for the prediction of B-cell epitopes, enabling immunologists and clinicians to identify the most promising epitopes for characterization in the laboratory. A sufficient number of available B-cell epitopes are indispensable for establishing the prediction models. To our knowledge, some popular databases associated with the B-cell epitopes are proposed and widely used in the immunoinformatics. In this chapter, we present an overview of the important databases and introduce how to compile datasets for the development of B-cell epitope prediction tools.
Sorption of phenanthrene onto the natural sediment with low organic carbon content (OC%), organic-free sediment, and kaolinite was investigated through isotherm experiments. Effects of cosolutes (pyrene, 4-n-nonyphenol (NP), and humic acid (HA)) on phenanthrene sorption were also studied by comparing apparent solid-water distribution coefficients (K d (app)) of phenanthrene. Two addition sequences, including "cosolute added prior to phenanthrene" and "cosolute and phenanthrene added simultaneously," were adopted. The Freundlich model fits phenanthrene sorption on all 3 sorbents well. The sorption coefficients on these sorbents were similar, suggesting that mineral surface plays an important role in the sorption of hydrophobic organic contaminants on low OC% sediments. Cosolutes could affect phenanthrene sorption on the sorbents, which depended on their properties, concentrations, and addition sequences. Pyrene inhibited phenanthrene sorption. Sorbed NP inhibited phenanthrene sorption at low levels and promoted sorption at high levels. Similar to NP, effect of HA on phenanthrene sorption onto the natural sediment depended on its concentrations, whereas, for the organic-free sediment and kaolinite, preloading of HA at high levels led to an enhancement in phenanthrene K d (app) while no obvious effect was observed at low HA levels; dissolved HA could inhibit phenanthrene sorption on the two sorbents.
Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) have been reported to be effective in the treatment of esophageal and esophagogastric junction cancers. The aim of this study was to detect the frequency of EGFR mutation and expression in Chinese patients with esophageal, esophagogastric junction and gastric cancers, and to clarify the value of EGFR mutation and expression in predicting the efficacy of TKI in the treatment of these tumors.
To investigate the expression and clinical significance of phosphatase and tensin homology deleted on ehromosome ten (PTEN) and hypoxia-inducible factor 1 alpha (HIF-1?) in sinonasal inverted papilloma (SNIP) of different pathological grades.
We describe here the metagenomics-derived viral sequences detected in beef, pork, and chicken purchased from stores in San Francisco. In beef we detected four previously reported viruses (two parvoviruses belonging to different genera, an anellovirus, and one circovirus-like virus) and one novel bovine polyomavirus species (BPyV2-SF) whose closest relatives infect primates. Detection of porcine hokovirus in beef indicated that this parvovirus can infect both ungulate species. In pork we detected four known parvoviruses from three genera, an anellovirus, and pig circovirus 2. Chicken meat contained numerous gyrovirus sequences including those of chicken anemia virus and of a novel gyrovirus species (GyV7-SF). Our results provide an initial characterization of some of the viruses commonly found in US store-bought meats which included a diverse group of parvoviruses and viral families with small circular DNA genomes. Whether any of these viruses can infect humans will require testing human sera for specific antibodies.
A novel surface-enhanced Raman scattering (SERS) detection system is developed for proteins and nucleic acids based on a triple-helix molecular switch for multiple cycle signal amplification, achieving high sensitivity, universality, rapid analysis, and high selectivity.
Core/shell/shell structured Fe3O4/SiO2/Gd2O(CO3)2 nanoparticles were successfully synthesized. Their properties as a new type of T1-T2 dual model contrast agent for magnetic resonance imaging were investigated. Due to the introduce of a separating SiO2 layer, the magnetic coupling between Gd2O(CO3)2 and Fe3O4 could be modulated by the thickness of SiO2 layer and produce appropriate T1 and T2 signal. Additionally, the existence of Gd(3+) enhances the transverse relaxivity of Fe3O4 possibly because of the magnetic coupling between Gd(3+) and Fe3O4. The Fe3O4/SiO2/Gd2O(CO3)2 nanoparticles exhibit good biocompatibility, showing great potential for biomedical applications.
Previously, we observed an acid-induced short-term wall extension in Flammulina velutipes apical stipes during a 15 min period after a change from a neutral to an acidic pH. This acid-induced stipe wall extension was eliminated by heating and reconstituted by a snail expansin-like protein, although we failed to isolate any endogenous expansin-like protein from F. velutipes because of its limited 1 mm fast elongation region. In this study, we report that Coprinopsis cinerea stipes possess a 9 mm fast elongation apical region, which is suitable as a model material for wall extension studies. The elongating apical stipe showed two phases of acid-induced wall extension, an initial quick short-term wall extension during the first 15 min and a slower, gradually decaying long-term wall extension over the subsequent 2 h. After heating or protein inactivation pretreatment, apical stipes lost the long-term wall extension, retaining a slower short-term wall extension, which was reconstituted by an expansin-like snail protein. In contrast, the non-elongating basal stipes showed only a weaker short-term wall extension. We propose that the long-term wall extension is a protein-mediated process involved in stipe elongation, whereas the short-term wall extension is a non-protein mediated process not involved in stipe elongation.
It is of vital significance to conduct active postmarketing surveillance of Chinese medicine, as an active response to laws, rules and guidelines issued by the China Food and Drug Administration. These will provide technological support in evaluating adverse drug reactions (ADRs) or adverse drug events (ADEs). The expert consensus for postmarketing surveillance focuses on two surveillance designs; one is a large sample registry study to explore general population ADR/ADE characteristics, the other is a nested case-control study to explore the characteristic and mechanisms of ADRs.
Numerous studies have revealed the presence of T helper 17 (Th17) cells in pathologic intervertebral disk (IVD) tissues and the contribution of Th17-associated cytokines to the development of this disease. However, the pre- and postoperative changes in the proportion of Th17 cells and the concentration of IL-17 in the peripheral blood of patients with IVD degeneration are not clear. The levels of Th17 frequency and the interleukin-17 (IL-17) concentration in peripheral blood from patients and volunteers were examined by flow cytometry and by enzyme-linked immunosorbent assay (ELISA), respectively. The clinical results were evaluated using the visual analogue scale (VAS). These results were subjected to a correlation analysis. Compared with the normal controls, the proportion of Th17 cells and the concentration of IL-17 were significantly increased preoperatively in patients with IVD degeneration. Postoperatively, the levels of Th17 cells and the expression of IL-17 were dramatically decreased. The correlation analysis of the VAS pain scores, Th17 cell frequency, and IL-17 concentration, including the pre- and postoperative levels and the changes induced by the surgery, revealed a positive correlation. The authors' results explain the contribution of Th17 cells and IL-17 to the pain sensation experienced by patients with IVD degeneration. These 2 factors may be good indicators for the evaluation of the surgical outcome of patients with lumbar disk herniation.
The p53 and nuclear factor ?B (NF-?B) pathways play crucial roles in human cancer development. Simultaneous targeting of both pathways is an attractive therapeutic strategy against cancer. In this study, we report an antitumor molecule that bears a pyrrolo[3,4-c]pyrazole scaffold and functions as an enantiomeric inhibitor against both the p53-MDM2 interaction and the NF-?B activation. It is a first-in-class enantiomeric inhibitor with dual efficacy for cancer therapy. Synergistic effect was observed in vitro and in vivo. Docking and molecular dynamics simulation studies further provided insights into the nature of stereoselectivity.
Biofilm detachment often has detrimental effects such as pipe obstruction and infection, yet the detachment mechanisms underlying dispersal remain largely unknown. In this study, a stress response mechanism known as glutathione-gated potassium efflux (GGKE) was evaluated as an active detachment mechanism in the dispersal of Pseudomonas aeruginosa biofilms. N-ethylmaleimide (NEM) was used to activate potassium efflux proteins (Kef) associated with the GGKE pathway. This stress response mechanism was hypothesized to lead to altered cation concentration, which can potentially affect polymer bridging in biofilms, and ultimately cause biofilm detachment. Results showed the activation of GGKE by NEM exposure caused biofilm detachment without inducing a measurable change in viability, and detached biomass concentration and composition were dependent on NEM concentration. More detached biomass was observed with higher concentrations of NEM, with a trend of increasing polymer detachment. The detachment was likely resulting from a weakened biofilm structural integrity induced by bridge denaturing from GGKE activation. This study is important in understanding biofilm detachment from engineered systems such as membrane aerated bioreactors.
As an important method for building blocks synthesis, whole cell biocatalysis is hindered by some shortcomings such as unpredictability of reactions, utilization of opportunistic pathogen, and side reactions. Due to its biological and extensively studied genetic background, Pseudomonas putida KT2440 is viewed as a promising host for construction of efficient biocatalysts. After analysis and reconstruction of the lactate utilization system in the P. putida strain, a novel biocatalyst that only exhibited NAD-independent d-lactate dehydrogenase activity was prepared and used in l-2-hydroxy-carboxylates production. Since the side reaction catalyzed by the NAD-independent l-lactate dehydrogenase was eliminated in whole cells of recombinant P. putida KT2440, two important l-2-hydroxy-carboxylates (l-lactate and l-2-hydroxybutyrate) were produced in high yield and high optical purity by kinetic resolution of racemic 2-hydroxy carboxylic acids. The results highlight the promise in biocatalysis by the biotechnologically important organism P. putida KT2440 through genomic analysis and recombination.
Ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit, has been found to be associated with multiple physiological and pathophysiological functions. However, its effects and mechanisms in non-small cell lung cancer (NSCLC) still remain unknown. Here, we showed that expressions of total rpS6 and phosphorylation rpS6 (p-rpS6) were both significantly overexpressed in NSCLC. Further survival analysis revealed the shortened overall survival (OS) and relapse-free survival (RFS) in p-rpS6 overexpressed patients and confirmed it as an independent adverse predictor. Stable downregulation of rpS6 in lung adenocarcinoma A549 and squamous cell carcinoma H520 cell lines was then achieved by two specific small hairpin RNA (shRNA) lentiviruses separately. Subsequent experiments showed that downregulation of rpS6 dramatically inhibited cell proliferation in vitro and tumorigenicity in vivo. Moreover, loss of rpS6 promoted cells arrested in G0-G1 phase and reduced in G2-M phase, along with the expression alterations of relative proteins. However, no notable change in apoptosis was observed. Collectively, these results suggested that rpS6 is overactivated in NSCLC and its downregulation suppresses the growth of NSCLC mainly by inducing G0-G1 cell cycle arrest rather than apoptosis.
Aberrant expression and activation of FGFR3 is associated with disease states including bone dysplasia and malignancies of bladder, cervix, and bone marrow. MS analysis of protein-phosphotyrosine in multiple myeloma cells revealed a prevalent phosphorylated motif, D/EYYR/K, derived from the kinase domain activation loops of tyrosine kinases including FGFR3 corresponding to a recognition sequence of phosphotyrosine phosphatases PTPN1. Knockdown of PTPN1 or the related enzyme PTPN2 by RNAi resulted in ligand-independent activation of FGFR3. Modulation of FGFR3 activation loop phosphorylation by both PTPN1 and PTPN2 was a function of receptor trafficking and PTP compartmentalization. The FGFR3 activation loop motif DYYKK(650) is altered to DYYKE(650) in the oncogenic variant FGFR3(K650E) , and consequently it is constitutively fully activated and unaffected by activation loop phosphorylation. FGFR3(K650E) was nevertheless remarkably sensitive to negative regulation by PTPN1 and PTPN2. This suggests that in addition to modulating FGFR3 phosphorylation, PTPN1 and PTPN2 constrain the kinase domain by fostering an inactive-state. Loss of this constraint in response to ligand or impaired PTPN1/N2 may initiate FGFR3 activation. These results suggest a model wherein PTP expression levels may define conditions that select for ectopic FGFR3 expression and activation during tumorigenesis. This article is protected by copyright. All rights reserved.
Despite the exciting advances in cancer therapy over past decades, tumor metastasis remains the dominate reason for cancer-related mortality. In present work, DNA-wrapped gold nanorods with doxorubicin (DOX)-loading (GNR@DOX) were developed for treatment of metastatic breast cancer via a combination of chemotherapy and photothermal ablation. The GNR@DOX nanoparticles induced significant temperature elevation and DOX release upon irradiation with near infrared (NIR) light as shown in the test tube studies. It was found that GNR@DOX nanoparticles in combination with laser irradiation caused higher cytotoxicity than free DOX in 4T1 breast cancer cells. Animal experiment with an orthotropic 4T1 mammary tumor model demonstrated that GNR@DOX nanoplatform significantly reduced the growth of primary tumors and suppressed their lung metastasis. The Hematoxylin and Eosin (H&E) and immunohistochemistry (IHC) staining assays confirmed that the tumor growth inhibition and metastasis prevention of GNR@DOX nanoparticles were attributed to their abilities to induce cellular apoptosis/necrosis and ablate intratumoral blood vessels. All these results suggested a considerable potential of GNR@DOX nanoplatform for treatment of metastatic breast cancer.
Fluorescence ratio imaging is currently being used to quantitatively detect biologically active molecules in biosystems; however, two excitations of most existing fluorescent ratiometric probes account for cumbersome operating conditions for imaging. Thus, a fluorescent ratiometric probe, 6-methoxyquinolinium-dansyl (MQ-DS), for Cl(-) with single excitation/dual maximum emission has been developed. MQ-DS can preferably localize into lysosomes and display excellent photostability. Upon excitation at a single wavelength, it responds precisely and instantaneously to changes in Cl(-) concentrations, and it can be conveniently utilized to implement real-time fluorescence ratio imaging to quantitatively track alterations in Cl(-) levels inside cells treated under various pH conditions, and also in zebrafish with acute wounds. The successful application of the new probe in bioimaging may greatly facilitate a complete understanding of the physiological functions of Cl(-) .
An increased population of CD4(+)CD25(high)Foxp3(+) regulatory T cells (Tregs) in the tumor-associated microenvironment plays an important role in cancer immune evasion. However, the underlying mechanism remains unclear. Here we observed an increased secretion of miR-214 in various types of human cancers and mouse tumor models. Tumor-secreted miR-214 was sufficiently delivered into recipient T cells by microvesicles (MVs). In targeted mouse peripheral CD4(+) T cells, tumor-derived miR-214 efficiently downregulated phosphatase and tensin homolog (PTEN) and promoted Treg expansion. The miR-214-induced Tregs secreted higher levels of IL-10 and promoted tumor growth in nude mice. Furthermore, in vivo studies indicated that Treg expansion mediated by cancer cell-secreted miR-214 resulted in enhanced immune suppression and tumor implantation/growth in mice. The MV delivery of anti-miR-214 antisense oligonucleotides (ASOs) into mice implanted with tumors blocked Treg expansion and tumor growth. Our study reveals a novel mechanism through which cancer cell actively manipulates immune response via promoting Treg expansion.
Severe acne presents sexual dimorphism in its incidence in Chinese population. It is more prevalent in males. To assess the possible Y chromosomal contribution to severe acne risk in Han Chinese males, we analyzed 2041 Y chromosomal SNPs (Y-SNPs) in 725 severe acne cases and 651 controls retrieved from our recent genome-wide association study data. After data filtering, we assigned 585 cases and 494 controls into 12 Y chromosomal haplogroups based on 307 high-confidence Y-SNPs. No statistically significant difference in the distribution of Y chromosomal haplogroup frequencies was observed between the case and control groups. Our results showed a lack of association between the incidence of severe acne and the different Y chromosomal haplogroup in the Han Chinese population.
The tumor suppressor protein prostate apoptosis response-4 (Par-4), which is secreted by normal cells, selectively induces apoptosis in cancer cells. We identified a 3-arylquinoline derivative, designated Arylquin 1, as a potent Par-4 secretagogue in cell cultures and mice. Mechanistically, Arylquin 1 binds vimentin, displaces Par-4 from vimentin for secretion and triggers the efficient paracrine apoptosis of diverse cancer cells. Thus, targeting vimentin with Par-4 secretagogues efficiently induces paracrine apoptosis of tumor cells.
Wear-particle-induced osteolysis is considered to be the main reason for revision after arthroplasty. Although the exact mechanism remains unclear, inflammatory osteoclastogenesis plays an important role in this process. Strontium ranelate (SR) was found to have a therapeutic effect on osteoporosis in postmenopausal women. Based on prior studies, the present authors hypothesized that SR prevents wear-particle-induced osteolysis through restraining inflammatory osteoclastogenesis. The present study used 80 male C57BL/J6 mice to test this hypothesis in a murine osteolysis model. All experimental animals were randomly divided into four groups: a control group; a SR group; a titanium group; and a titanium+SR group. Once titanium particles had been implanted in mice, the mice were administered SR (900mgkg(-1)day(-1)) by gavage for 14days. After 14days, the calvaria were collected for micro-computed tomography (?CT), histological and molecular analysis. The results of ?CT and histomorphometric analysis demonstrated that SR markedly inhibited bone resorption and the generation of tartrate-resistant acid-phosphatase-positive cells in vivo, compared with titanium-stimulated calvaria. Reverse transcription polymerase chain reaction and ELISAs showed that SR stimulated the mRNA and protein expression of osteoprotegerin, and inhibited gene and protein expression of receptor activators of nuclear factor-kappa B ligand in titanium-particle-charged calvaria. In addition, SR obviously reduced the secretion of tumor necrosis factor-? and interleukin-1? in the calvaria of the titanium group. It was concluded that SR inhibits titanium-induced osteolysis by restraining inflammatory osteoclastogenesis, and that it could be developed as a new drug to prevent and treat aseptic loosening.
Mitochondrial dysfunction has been widely reported in schizophrenia patients. To dissect the matrilineal structure of Han Chinese with or without schizophrenia and to decipher the maternal influence and evolutionary history of schizophrenia, a total of 1212 schizophrenia patients and 1005 matched healthy controls, all of Han Chinese origin, were recruited in Hunan Province, China. We classified haplogroup for each individual based on mitochondrial DNA (mtDNA) sequence variations and compared the haplogroup distribution pattern between cases and controls. Haplogroup B5a presented a higher frequency in cases than in controls (P = 0.02, OR = 1.67, 95% CI = [1.09, 2.56]), and this result could be confirmed by permutation analysis. Age estimation of haplogroup B5a in cases revealed a much younger age than that of controls, which was coincident with the Northern Hemisphere deglaciation at the end of the Last Glacial Maximum. Analysis of complete mtDNA in five patients belonging to haplogroup B5a showed that this background effect might be caused by haplogroup-defining variants m.8584G>A and m.10398A>G. Our results showed that matrilineal risk factor for schizophrenia had an ancient origin and might acquire a predisposing effect on schizophrenia due to the environment change and/or orchestration with other nuclear genetic factors appeared recently in human evolutionary history.
Nanographene oxide (NGO) with a non-sheddable poly(ethylene glycol) (PEG) coating has been used for chemo-photothermal therapy. However, the drug release of PEGylated NGO (NGO-PEG) with an amine bond is adversely affected by the diffusion barrier effect of PEG shells. Here, we developed a simple new method for the preparation of biodegradable PEGylated NGO conjugates (NGO-SS-PEG) with cleavable disulfide bonds for rapid drug release and more efficiently chemo-photothermal therapy. The glutathione (GSH)-induced and photothermal-mediated intracellular release of doxorubicin (DOX) from NGO-SS-PEG was studied in A549 cells using confocal laser scanning microscopy and flow cytometry analysis. In vivo cytotoxicity experiments were performed on chemo-photothermal therapy. Furthermore, we presented a comparative study of intracellular drug release and biological efficacy between NGO-SS-PEG/DOX and NGO-PEG/DOX. The results demonstrated that the rapid drug release from the NGO-SS-PEG conjugates with sheddable PEG was triggered upon the stimulus of high GSH levels inside A549 cells. Interesting, the DOX release mediated by the photothermal effect from the NGO-SS-PEG conjugates was found to be more obvious than that for NGO-PEG. Additionally, NGO-SS-PEG showed a higher efficacy than NGO-PEG for anti-tumor therapy compared with NGO-PEG. Thus, NGO-SS-PEG can improve therapeutic efficacy and is an attractive drug nanocarrier.
There is a rising interest in the use of patient-specific instrumentation (PSI) during total knee arthroplasty (TKA). The goal of this meta-analysis was to compare PSI with conventional instrumentation (CI) in patients undergoing TKA.
Stem cells from the apical papilla (SCAP) have odontogenic potential, which plays a pivotal role in the root dentin development of permanent teeth. Human bone morphogenetic protein 2 (BMP2) is a well-known gene that participates in regulating the odontogenic differentiation of dental tissue?derived stem cells. However, little is known regarding the effects of the BMP2 gene on the proliferation and odontogenic differentiation of SCAP. This study aimed to evaluate the odontogenic differentiation potential of lentiviral?mediated BMP2 gene?transfected human SCAP (SCAP/BMP2) in vitro. SCAP were isolated by enzymatic dissociation of human teeth apical papillae. The multipotential of SCAP was verified by their osteogenic and adipogenic differentiation characteristics. The phenotype of SCAP was evaluated by flow cytometry (FCM). The proliferation status of the blank vector?transfected SCAP (SCAP/Vector) and SCAP/BMP2 was analyzed by a cell counting kit-8 (CCK?8). Odontogenic genes, including alkaline phosphatase (ALP), osteocalcin (OCN), dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP1) of the two groups of cells were evaluated by quantitative polymerase chain reaction (qPCR). ALP staining and alizarin red (AR) staining of the cells was performed on the 16th day after transfection. In vitro results of CCK-8, qPCR, ALP and AR staining demonstrated that: ?) SCAP/BMP2 had a comparable proliferation rate to SCAP/Vector; ?) SCAP/BMP2 presented significantly better potential to differentiate into odontoblasts compared to SCAP/Vector by upregulating ALP, OCN, DSPP and DMP1 genes; ?) more ALP granules and mineralized deposits were formed by SCAP/BMP2 as compared to SCAP/Vector. The results suggested that lentiviral-mediated BMP2 gene transfection enhances the odontogenic differentiation capacity of human SCAP in vitro.
Changes in cadmium (Cd) accumulation, distribution, and chemical form in rice seedling in the joint presence of different concentrations of sulfur (S) remain almost unknown. Therefore, the indoor experiments were performed to determine the accumulation, sub-cellular distribution and chemical forms of Cd under three S levels in rice seedling for the first time. The result showed that Cd accumulation in rice roots was more than in shoots. Sub-cellular distribution of Cd in rice roots and shoots indicated that the largest proportion of Cd accumulated in cell walls and soluble fractions. As S supply increased, the proportion of Cd in cell walls reduced, while it increased in the soluble fractions. The majority of Cd existed in inorganic form, and then gradually changed to organic forms that included pectates and proteins with increased S supply. The results showed that S supply significantly influenced Cd accumulation, distribution, and chemical forms, suggesting that S might provide the material for the synthesis of sulfhydryl protein and thereby affect Cd stress on plants. These observations provided a basic understanding of potential ecotoxicological effects of joint Cd and S exposure in the environment.
This study established a numerical model to investigate the degradation mechanism and behavior of bioabsorbable cardiovascular stents. In order to generate the constitutive degradation material model, the degradation characteristics were characterized with user-defined field variables. The radial strength bench test and analysis were used to verify the material model. In order to validate the numerical degradation model, in vitro bench test and in vivo implantation studies were conducted under physiological and normal conditions. The results showed that six months of degradation had not influenced the thermodynamic properties and mechanical integrity of the stent while the molecular weight of the stents implanted in the in vivo and in vitro models had decreased to 61.8% and 68.5% respectively after six month's implantation. It was also found that the degradation rate, critical locations and changes in diameter of the stents in the numerical model were in good consistency in both in vivo and in vitro studies. It implies that the numerical degradation model could provide useful physical insights and prediction of the stent degradation behavior and evaluate, to some extent, the in-vivo performance of the stent. This model could eventually be used for design and optimization of bioabsorbable stent.
Peripheral nerve injury (PNI) is a common disease that often results in axonal degeneration and the loss of neurons, ultimately leading to limited nerve regeneration and severe functional impairment. Currently, there are no effective treatments for PNI. In the present study, we transduced conserved dopamine neurotrophic factor (CDNF) into mesenchymal stem cells (MSCs) in collagen tubes to investigate their regenerative effects on rat peripheral nerves in an in vivo transection model. Scanning electron microscopy of the collagen tubes demonstrated their ability to be resorbed in vivo. We observed notable overexpression of the CDNF protein in the distal sciatic nerve after application of CDNF-MSCs. Quantitative analysis of neurofilament 200 (NF200) and S100 immunohistochemistry showed significant enhancement of axonal and Schwann cell regeneration in the group receiving CDNF-MSCs (CDNF-MSCs group) compared with the control groups. Myelination thickness, axon diameter and the axon-to fiber diameter ratio (G-ratio) were significantly higher in the CDNF-MSCs group at 8 and 12 weeks after nerve transection surgery. After surgery, the sciatic functional index, target muscle weight, wet weight ratio of gastrocnemius muscle and horseradish peroxidase (HRP) tracing demonstrated functional recovery. Light and electron microscopy confirmed successful regeneration of the sciatic nerve. The greater numbers of HRP-labeled neuron cell bodies and increased sciatic nerve index values (SFI) in the CDNF-MSCs group suggest that CDNF exerts neuroprotective effects in vivo. We also observed higher target muscle weights and a significant improvement in muscle atrophism in the CDNF-MSCs group. Collectively, these findings indicate that CDNF gene therapy delivered by MSCs is capable of promoting nerve regeneration and functional recovery, likely because of the significant neuroprotective and neurotrophic effects of CDNF and the superior environment offered by MSCs and collagen tubes.
The nuclear transcription factor c-Myc is a member of the Myc gene family with multiple functions and located on band q24.1 of chromosome 8. The c-Myc gene is activated by chromosomal translocation, rearrangement, and amplification. Its encoded protein transduces intracellular signals to the nucleus, resulting in the regulation of cell proliferation, differentiation, and apoptosis, and has the ability to transform cells and bind chromosomal DNA. c-Myc also plays a critical role in malignant transformation. The abnormal over-expression of c-Myc is frequently observed in some tumors, including carcinomas of the breast, colon, and cervix, as well as small-cell lung cancer, osteosarcomas, glioblastomas, and myeloid leukemias, therefore making it a possible target for anticancer therapy. In this minireview, we summarize unique characteristics of c-Myc and therapeutic strategies against cancer using small molecules targeting the oncogene, and discuss the prospects in the development of agents targeting c-Myc, in particular G-quadruplexes formed in c-Myc promoter and c-Myc/Max dimerization. Such information will be of importance for the research and development of c-Myc-targeted drugs.
Type 2 diabetes is a serious and common chronic disease resulting from a complex inheritance-environment interaction along with other risk factors such as obesity and sedentary lifestyle. Type 2 diabetes and its complications constitute a major worldwide public health problem, affecting almost all populations in both developed and developing countries with high rates of diabetes-related morbidity and mortality. The prevalence of type 2 diabetes has been increasing exponentially, and a high prevalence rate has been observed in developing countries and in populations undergoing "westernization" or modernization. Multiple risk factors of diabetes, delayed diagnosis until micro- and macro-vascular complications arise, life-threatening complications, failure of the current therapies, and financial costs for the treatment of this disease, make it necessary to develop new efficient therapy strategies and appropriate prevention measures for the control of type 2 diabetes. Herein, we summarize our current understanding about the epidemiology of type 2 diabetes, the roles of genes, lifestyle and other factors contributing to rapid increase in the incidence of type 2 diabetes. The core aims are to bring forward the new therapy strategies and cost-effective intervention trials of type 2 diabetes.
Xuanwei and Fuyuan, two counties located in southwest China, are areas with known high lung cancer incidence. Pollution relative to coal combustion, especially serious air pollution generated by burning smoky coals in unvented households, has been thought to be the most predominant cause. Possible inorganic carcinogenic matter including radon in air and arsenic, lead, chromium, cadmium, nickel, and beryllium in water, soil, and coal were sampled and examined to find the current pollution status, distributions, characteristics, and relationships to the lung cancer incidence. The concentrations of mercury in air of Xuanwei and Fuyuan ranged from 1.7 to 205.3 ng/m3 (indoor), 1.3 to 7.5 ng/m3 (ambient). No radon concentration exceeded the World Health Organization standard. Results indicated that household stove improvement by changing stoves from unvented to vented obviously alleviated the indoor air pollution of carcinogenic metals. Most of the carcinogenic metals were also found at very low levels in water and soil, which therefore had little influence on human health. Concentrations of these elements at different sites did not vary in any relation to lung cancer incidence. The study described in this article added basic data; the results of the authors study will be helpful in determining pollution status and to future studies on the etiology of lung cancer.
To retrospectively analyze the safety and efficacy of mechanical thrombectomy combined with pharmacologic thrombolysis to treat non-acute and symptomatic portal vein thrombosis (PVT) using an intrahepatic portosystemic shunt (IPS) assisted by percutaneous transhepatic approach.
There was no standard treatment for hepatocellular carcinoma with portal vein tumour thrombosis (PVTT). This prospective, randomised, two-arm clinical trial aims to investigate the feasibility, safety and effectiveness of transarterial chemoembolisation (TACE) combined with the endovascular implantation of an iodine-125 seed strand for the treatment of hepatocellular carcinoma with portal vein tumour thrombosis versus conventional TACE.
16S rDNA is a gold marker for categorizing bacterial or identifying microbial community. However, the bias in prevalence metagenomic studies, whether in experiments or data analyses, greatly limits its clinical utility. To evaluate the efficiency of present metagenomic methods, 7 mixed simulated samples with 10 bacteria were sequenced at different concentration. V3 region of 16S rDNA were selected as the target to compare the proportion of the bacteria. We found the number of target sequences of individual simulated strain were quite different, from 1 fold to 1000 fold, which help us have a better understanding of the microbe community in the identified environment. However, for a given bacteria with same proportion but in different concentration in a sample, the observed percentage of 16S rDNA was similar except at very low concentration, which even cannot detected by RT-PCR. These results confirmed that the comparative microbiome with 16S rDNA in a certain sample is efficiency enough to detect potential infectious pathogens, but the absolute proportion of 16S rDNA in the sample.
Famitinib is a novel and potent multitargeting receptor tyrosine kinase inhibitor. The phase I clinical study showed that famitinib was well tolerated and had a broad anti-tumor spectrum. The purpose of this study was to examine the efficacy and safety of famitinib for the treatment of metastatic renal cell carcinoma (mRCC).
Either oxaliplatin- or irinotecan-containing regimen could receive a good effectiveness in patients with metastatic colorectal cancer as the first-line chemotherapy, but not all patients would benefit from the treatment they have received. This study was to investigate the role of single nucleotide polymorphisms (SNPs) of methylenetetrahydrofolate reductase (MTHFR) and ATP-binding cassette sub-family G member 2 (ABCG2) in selecting the most appropriate treatment for individual patients. Ninety-two metastatic colorectal cancer patients treated with first-line 5-fluoropyrimidine (5-FU), leucovorin, and oxaliplatin (FOLFOX), capecitabine, and oxaliplatin (XELOX) and sixty-two patients receiving 5-FU, leucovorin, and irinotecan (FOLFIRI) were reviewed. The SNPs of MTHFR and ABCG2 were detected using gene sequencing method after DNA PCR amplification, which was extracted from peripheral blood karyocytes. Clinical characteristics and gene polymorphisms were evaluated in univariate and multivariate analysis as predictive factors for response rate (RR) and progression-free survival (PFS). In patients bearing 2-4 genotypes of MTHFR 677C/C, MTHFR 1298 A/C or C/C, ABCG2 34G/G, and ABCG2 421C/A or A/A, those who received oxaliplatin-based chemotherapy achieved a higher RR (41.7 vs. 18.8 %, P = 0.027) and longer median PFS (mPFS) than irinotecan-based therapy [8.9 vs. 7.1 m, FOLFIRI: hazard ratio (HR) = 1.722, 95 % confidence interval (CI) 1.026-2.892, P = 0.040, compared with FOLFOX/XELOX]; on the contrary, patients carrying 0 or 1 above genotype exhibited better outcomes after receiving FOLFIRI chemotherapy (mPFS: 9.3 vs. 6.4 m, FOLFIRI: HR = 0.422, 95 % CI 0.205-0.870, P = 0.019, compared with FOLFOX/XELOX). Combination of SNPs with MTHFR and ABCG2 may play a role in helping clinicians to select first-line chemotherapy for patients with metastatic colorectal cancer.
Abstract Purpose: The aim of this study was to evaluate the feasibility of natural orifice translumenal endoscopic surgery (NOTES(®); American Society for Gastrointestinal Endoscopy [Oak Brook, IL] and Society of American Gastrointestinal and Endoscopic Surgeons [Los Angeles, CA]) for the surgical management of long-segment Hirschsprungs disease. Patients and Methods: Three children with long-segment Hirschsprungs disease were enrolled in this study. In all three cases the transition zone was proximal to the splenic flexure, with too long a segment of distal aganglionic colon to perform an isolated transanal pull-through. Our procedure was as follows. A rectal mucosectomy was performed starting 0.5?cm proximal to the dentate line and extending proximally to the level of the intraperitoneal rectum. Three cannulas were inserted through the muscular sleeve into the abdominal cavity. The mesocolon, lateral peritoneum, and greater omentum were ligated and divided in order to mobilize the colon. After mobilization, the aganglionic distal bowel segment was pulled through the anus and resected. Finally the colo-anal anastomosis was created. Results: All three operations were successfully performed without intraoperative complications. No additional ports or conversion to an open procedure was required. The operative times were 242, 195, and 174 minutes, respectively. All three children were discharged without complication with follow-up for at least 1 year. One year after the procedure the 3 patients were stooling one to three times per day, with no fecal soiling or constipation. Conclusions: This NOTES procedure may be a safe and feasible option for the surgical treatment of long-segment Hirschsprungs disease.
The objective of this study was to evaluate the effect of adsorption on the biological treatment process of wastewater. In the absence of substrate in the water, activated sludge developed well in the first hour, indicating that the growth of microorganism was not directly related to substrate concentration and the dissolved organic matter in the water assays were performed, no organic matter was detected out, revealing that there was no desorption in the activated sludge adsorption process. Activated sludge batch growth experiments in the presence of different adsorption capacities indicated that specific growth rate increased as specific adsorption capacity increased. The experiment on the relationship of adsorption capacity and substrate concentration or sludge concentration was also carried out. Specific adsorption capacity increased as sludge load increased, presenting linear correlation. The experiment results showed that adsorption should be taken into account in the study of the biological treatment process of wastewater.
A fluoroimmunoassay towards aflatoxin B1 (AFB1) was presented using quantum dots as the fluorescent label. The CdTe QDs were successfully linked to the monoclonal antibody against AFB1. Based on the conjugated complexes, a novel direct competitive fluorescence-linked immunosorbent assay (cFLISA) was developed for AFB1 detection. The 50% inhibition value (IC50) of the cFLISA was 0.149ng/mL in peanuts matrix. The method performance included the limit of detection (LOD) of 0.016ng/mL and considerable recoveries of 85-117% at three fortification levels (0.075, 0.15, and 0.3ng/g) from spiked AFB1 blank peanuts samples, along with coefficients of variation (CVs) below 10%. The cFLISA provided an alternative of rapid and sensitive detection for AFB1 and, moreover provided great potential for multiplexed mycotoxins determination simultaneously.
Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol-anchored 123-amino acid protein related to the cell proliferation inhibition and/or cell death induction activity which has attracted considerable attention as a candidate gene for gastric cancer (GC) since it was first identified through genome-wide association approach. Since then, the relationship between PSCA polymorphisms (rs2294008, rs2976392) and GC has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 16 studies involving a total of 18,820 cases and 35,756 controls for the two widely studied polymorphisms of PSCA on genetic susceptibility for GC. Overall, the summary odds ratio for GC was 1.46 (95 % CI 1.30-1.69, P?10(-5)) and 1.49 (95 % CI 1.22-1.82, P?10(-4)) for PSCA rs2294008 and rs2976392 polymorphisms, respectively. Meanwhile, haplotype analyses of the two polymorphisms revealed a significant association between the combination of these alleles and GC risk. When stratifying for ethnicity, significantly increased risks were found for rs2294008 and rs2976392 polymorphism among East Asians in all genetic models, while no significant associations were observed for the rs2294008 polymorphism in Caucasians. In the stratified analyses according to histological type, and source of controls, evidence of gene-disease association was still obtained. In addition, our data indicate that rs2294008 of PSCA is involved in GC susceptibility and confer its effect primarily in noncardia tumors (OR?=?1.30, 95 % CI 1.12-1.53, P?10(-4)). Our findings demonstrated that rs2294008 and rs2976392 polymorphism of PSCA is a risk-conferring factor associated with increased GC susceptibility, especially in East Asians.
Almonds and almond skins are rich in fiber and other components that have potential prebiotic properties. In this study we investigated the prebiotic effects of almond and almond skin intake in healthy humans. A total of 48 healthy adult volunteers consumed a daily dose of roasted almonds (56 g), almond skins (10 g), or commercial fructooligosaccharides (8 g) (as positive control) for 6 weeks. Fecal samples were collected at defined time points and analyzed for microbiota composition and selected indicators of microbial activity. Different strains of intestinal bacteria had varying degrees of growth sensitivity to almonds or almond skins. Significant increases in the populations of Bifidobacterium spp. and Lactobacillus spp. were observed in fecal samples as a consequence of almond or almond skin supplementation. However, the populations of Escherichia coli did not change significantly, while the growth of the pathogen Clostridum perfringens was significantly repressed. Modification of the intestinal microbiota composition induced changes in bacterial enzyme activities, specifically a significant increase in fecal ?-galactosidase activity and decreases in fecal ?-glucuronidase, nitroreductase and azoreductase activities. Our observations suggest that almond and almond skin ingestion may lead to an improvement in the intestinal microbiota profile and a modification of the intestinal bacterial activities, which would induce the promotion of health beneficial factors and the inhibition of harmful factors. Thus we believe that almonds and almond skins possess potential prebiotic properties.
The spatial distribution and toxic effects of cadmium (Cd) in the joint presence of sulfur (S) in rice seedling remain almost unknown. Therefore, the indoor experiments test runs were performed to determine the accumulation and toxicity of Cd in presence of S for the first time. The results showed that S supply significantly reduced the Cd accumulation and toxicity due to the decrease of Cd availability. XRF observation results illustrated that in the single Cd treatments, Cd mainly distributed in the bottom of root, while equably existed in the shoot. Additionally, S addition could facilitate Cd transfer to the top of shoot and finally form the similar distribution trend for S and Cd, suggesting that S might increase the synthesis of thiol pool (such as PCs, GSH and NPT) and then chelate Cd, which further affected Cd translocation. Such observations have provided the useful information of potential ecotoxicological effects of Cd contamination in the environment.
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