We developed a novel method for the real-time monitoring of the delicate change in refractive index (RI) when DNA or RNA hybridize near a DNA-capped silver nanocube (AgNC) surface. This method offers an alternative platform in the quantitative analysis of the trace lung cancer-associated miRNAs in label-free detection.
The emergence and transmission of extensively drug-resistant tuberculosis (XDR-TB) pose an increasing threat to global TB control. This study aimed to identify patterns of evolution and transmission dynamics of XDR-TB in high-epidemic populations in China. We analyzed a total of 95 XDR-TB isolates collected from 2003 to 2009 in Chongqing, China. Eight drug resistance genes covering 7 drugs that define XDR-TB were amplified by PCR followed by DNA sequencing. Variable number of tandem repeats (VNTR)-16 loci genotyping and genotypic drug resistance profiles were used to determine the evolution or transmission pattern of XDR-TB strains. Our results indicated that the Beijing genotype was predominant (85/95, 89.5%) in XDR-TB strains and as high as 40.0% (38/95) isolates were distributed into 6 clusters based on VNTR-16 genotyping as well as drug resistance mutation profiles. All isolates of each cluster harbored as many as six identical resistance mutations in drug resistance genes rpoB, katG, inhA promoter, embB, rpsL, and gidB. Among the nine cases with continuous isolates from MDR to XDR, 4 cases belonged to acquired drug resistance, 4 cases were caused by transmission, and 1 case was due to exogenous superinfection. The XDR-TB epidemic in China is mainly caused by a high degree of clonal transmission but evolution from MDR to XDR and even superinfection with new XDR strain can also occur.
A three-surface model is proposed for the ray tracing of an imaging acousto-optic tunable filter (AOTF) in the optical design of an AOTF imaging system. The first and last surfaces are two refractive planes corresponding to the incident and exit facets of the AOTF, while the property of the second surface is defined particularly to describe the change of the ray trace owing to the interaction of the acoustic and optic waves. One parameter, the acoustic angle, is first corrected using the test tuning relation to compensate for the nonideality of the acoustic wave. The model has been verified with a two-piezotransducer AOTF to show its usefulness. The differences between the measured diffracted angles and the modeling value are below 0.01°. The comparison demonstrates the accuracy and the efficiency of the three-surface model.
Abstract This study was designed to detect characteristic compounds and evaluate the free radical scavenging capacity of the bamboo leaves extract and bamboo shavings extract (BSE). The antioxidant capacity of bamboo leaf n-butanol fraction (AOB) exhibited the highest total phenolic content (49.93%), total flavonoids content (24.11%), and characteristic flavonoids and phenolic acids, such as chlorogenic acid, caffeic acid, ferulic acid, p-coumaric acid, orientin, homoorientin, vitexin, and isovitexin. Available data obtained with in vitro models suggested that AOB had higher free radical scavenging capacity with IC50 values of 1.04, 4.48, 5.37, and 1.12??g/mL on DPPH(•), O2(•-), (•)OH, and H2O2, respectively, than the other two extracts, bamboo leaf water extract and BSE. The results indicated that the extracts from different parts of the bamboo possess excellent antioxidant activity, which can be used potentially as a readily accessible and valuable bioactive source of natural antioxidants.
Cancer-associated point mutations in isocitrate dehydrogenase 1 and 2 (IDH1, IDH2) confer a neomorphic enzymatic activity: the reduction of alpha-ketoglutarate (?KG) to D-2-hydroxyglutaric acid (2HG), which is proposed to act as an oncogenic metabolite by inducing hypermethylation of histones and DNA. While selective inhibitors of mutant IDH1 and IDH2 have been identified and are currently under investigation as potential cancer therapeutics, the mechanistic basis for their selectivity is not yet well-understood. A high-throughput screen for selective inhibitors of IDH1 bearing the oncogenic mutation R132H identified Compound 1, a bis-imidazole phenol that inhibits 2HG production in cells. We investigated the mode of inhibition of Compound 1 and a previously published IDH1 mutant inhibitor with a different chemical scaffold. Steady-state kinetics and biophysical studies show that both of these compounds selectively inhibit mutant IDH1 by binding to an allosteric site, and that inhibition is competitive with respect to Mg(2+). A crystal structure of Compound 1 complexed with R132H IDH1 indicates that the inhibitor binds at the dimer interface and makes a direct contact with a residue involved in binding of the catalytically essential divalent cation. These results show that targeting a divalent cation binding residue can enable selective inhibition of mutant IDH1, and suggest that differences in magnesium binding between wild-type and mutant enzymes may contribute to the inhibitors' selectivity for the mutant enzyme.
Effective biomarkers for early detection of ovarian cancer are needed. Our study previously showed that basement membrane protein, nidogen-1 plasma level was significantly increased in ovarian cancer patients. This study aimed to examine the plasma levels of nidogen-1 in a large patient population to evaluate its effectiveness in ovarian serous carcinoma and expression in tumor tissues.
Sleep is essential for basic survival as well as for optimal physical and cognitive performance in both human beings and animals. To investigate the effect of syringin on sleep of anesthetized mice and the potential mechanisms, 35 male Kunming mice were randomly divided into six experimental groups (n=5) and one control group (n=5). Sleep latency and sleep duration, as well as nitric oxide (NO) content and nitric oxide synthase (NOS) activity, were determined after syringin administration. The NO precursor L-Arginine (L-Arg) or NOS inhibitor NG-Nitro-L-arginine Methyl Ester (L-NAME) were administered alone or in combination with syringin, and time for sleep latency and duration was recorded. After intragastric administration of syringin, sleep latency decreased in a dose- and time-dependent manner, concomitant with increased sleep duration. The optimal sleep performance was obtained when syringin was given at a dose of 80 mg/kg for 8 consecutive days. Syringin significantly reduced NO concentration and NOS activity. Administration of L-Arg prolonged sleep latency and shortened sleep duration, and the effects were fully reversed by syringin co-administration. Administration of L-NAME induced a significant reduction in sleep latency and a corresponding increase in sleep duration, and co-administration of syringin further enhanced the effects. The finding of our study demonstrated that syringin could exert sleep-potentiating effects on anesthetized mice in a time- and dose-dependent manner, and these effects may be intimately correlated with the NO/NOS pathway. This article is protected by copyright. All rights reserved.
Abstract Objective: To evaluate the relationship between pulse pressure index (PPI) and carotid intima-media thickness (CIMT). Method: Observational trial was design and 342 patients newly diagnosed as hypertension without anti-hypertensive therapy were enrolled. According to the cut-off value of CIMT, 342 participants were divided into normal (0.9mm) and increased CIMT groups (??0.9mm). Baseline characteristics were compared, logistic regression analysis and receiver operating characteristic curve (ROC) were performed. Results: Approximately 34.2% of participants (n?=?117) were with CIMT???0.9?mm and participants in increased CIMT group were more elderly. Diastolic blood pressure was lower in increased CIMT group than normal group (79.3?±?10.8?mm Hg versus 83.8?±?9.4?mm Hg, p?0.001), whereas pulse pressure (PP) (59.3?±?20.2?mm Hg versus 53.6?±?15.5?mm Hg, p?=?0.004) and PPI (0.43?±?0.09 versus 0.38?±?0.08, p?0.001) were significantly higher in increased CIMT group. CIMTs were 1.11?±?0.11?mm and 0.76?±?0.12 in increased group and normal group respectively (p?0.001). After adjusted for the traditional risk factors, only PPI was found an independent determinant for CIMT increase, and the odd ratio was 1.644 (95% interval confidence 1.280-2.112, p?0.001). The ROC evaluations showed that area under the curve for PP to predict CIMT increase was 0.591?±?0.034, and PPI was 0.664?±?0.033. PPI was more powerful than PP in discriminating CIMT increase (p?=?0.006). Conclusion: PPI is a valuable parameter for the preliminary screening of hypertensive patients who have an increased risk of atherosclerosis.
Abstract 1. As a potential new drug candidate for cardiovascular protection and antitumor treatment, the physicochemical properties, gastrointestinal (GI) absorption behaviors and mechanisms of S-propargyl-cysteine (SPRC) were investigated in this study. 2. SPRC exhibited favorable solubility in aqueous media. The log P and log D values were low (?1.93?±?0.08). The pKa in the acidic and basic regions was 2.08?±?0.02 and 8.72?±?0.03, respectively. The isoelectric point was 5.40?±?0.02. SPRC was stable in the rat GI fluids, and showed no obvious adsorption and metabolism in the rat GI tract. 3. SPRC displayed poor gastric absorption and favorable intestinal absorption in the rat in situ GI perfusion model. Absorption rate constants (ka), hourly absorption percentage (P) and apparent permeability coefficient (Papp) of SPRC in the small intestine were ?0.77?±?0.06?h(-1), 59.25?±?4.02% and (7.99?±?0.88)?×?10(-5?)cm/s, respectively. Absorption of SPRC exhibited a certain dependence on physiological pH and absorption region. Absorption of SPRC was not inhibited by l-methionine and 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid. 4. SPRC showed favorable oral absorption. It can be categorized as a BCS class I drug. The membrane pore transport appeared to be one of the predominant absorption modes for SPRC.
In order to understand the genetic background and dissemination mechanism of carbrpenem resistance and fosfomycin resistance in Enterobacteriaceae isolates, a clinical E. coli isolate HS102707 and an Enteobacter aerogenes isolate HS112625 which were resistant to both carbrpenem and fosfomycin, and positive in both blaKPC-2 and fosA3 were studied. Beside, a clinical Klebsiella pneumonia isolate HS092839 which was resistant to carbapenem was also studied. A 70-kb plasmid was successfully transferred to recipient E.coli J53 by conjugation test. PCR and southern blot showed blaKPC-2 was located on this plasmid. The complete sequence of pHS102707 showed this plasmid, belonged to the P11 subfamily (IncP1), has a replication gene, several plasmid stable genes, an intact IV secretion system gene cluster and a composite transposon Tn1721-Tn3 harbored blaKPC-2. Interestingly, a composite IS26 transposon carrying fosA3 was inserted in Tn1721-tnpA gene in pHS102707 and pHS112625, leading to the disruption of Tn1721-tnpA and the deletion of Tn1721-tnpR. However, only an IS26 with a truncated Tn21-tnpR was inserted in pHS092839 at the same position. To our best knowledge, this is the first report of fosA3 and blaKPC-2 co-located in the same Tn1721-Tn3-like composite transposon on a novel IncP group plasmid.
ABSTRACT Ethnic factors pose major challenge to evaluating the treatment effect of a new drug in a targeted ethnic (TE) population in emerging regions based on the results from a multi-regional clinical trial (MRCT) (ICHE5, 1998). To address this issue with statistical rigor, Huang, et al. (2012) proposed a new design of a simultaneous global drug development program (SGDDP) which used weighted Z tests to combine the information collected from the non-targeted ethnic (NTE) group in the MRCT with that from the TE group in both the MRCT and a simultaneously designed local clinical trial (LCT). An important and open question in the SGDDP design was how to downweight the information collected from the NTE population to reflect the potential impact of ethnic factors and ensure that the effect size for TE patients is clinically meaningful. In this paper, we will relate the weight selection for the SGDDP to Method 1 proposed in the Japanese regulatory guidance published by the Ministry of Health, Labour and Welfare (MHLW) in 2007. Method 1 is only applicable when true effect sizes are assumed to be equal for both TE and NTE groups. We modified the Method 1 formula for more general scenarios, and use it to develop a quantitative method of weight selection for the design of the SGDDP which at the same time, also provides sufficient power to descriptively check the consistency of the effect size for TE patients to a clinically meaningful magnitude.
Staphylococcus aureus is a prominent human pathogen and is known to form L-forms in vitro and in vivo during infection. However, the conditions of L-form formation are not optimal and the mechanisms of L-form formation in this organism are unknown. Here we optimized the conditions of S. aureus unstable L-form formation and constructed a transposon mutant library and screened for mutants defective in unstable L-form formation. Our results revealed that 20% sucrose, 3.5% sodium chloride, 750-1000 units of penicillin and 33 oC were optimal conditions for L-form formation. Stationary phase cultures of S. aureus formed L-forms better than log phase cultures. The S. aureus L-form colonies showed typical "fried egg" morphology and the cells had deficient cell wall, morphological diversity, and stained Gram-negative. The mutant library screens identified 15 mutants deficient in L-form formation and sequencing analysis identified mutations in 8 genes and 3 intergenic regions. Real-time PCR analysis indicated that except gntK, 7 genes including glpF, glpK, NWMN_0623, NWMN_0843, NWMN_0333, NWMN_0872, and NWMN_1269 were preferentially expressed in L-forms compared to normal cell walled form (P?0.05). The identified genes involved in L-form growth mapped in the pathways for energy production, iron homeostasis, transporters, DNA repair, membrane biogenesis, and biosynthesis. Our findings shed new insight into the molecular basis of S. aureus unstable L-form formation and may have implications for development of novel drugs targeting S. aureus L-forms for improved treatment.
Analysis of oligosaccharides with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) remains challenging due to their low ionization efficiency. The sensitivity achieved by MS for oligosaccharides lags far behind that for proteins/peptides. Here, hydrazinonicotinic acid (HYNIC) is proposed as a new matrix to realize highly sensitive and selective analysis of oligosaccharides in MALDI-MS. The detection limit of maltoheptaose provided by HYNIC is as low as 1 amol, which is five orders of magnitude lower than that provided by the traditional matrix 2,5-dihydroxybenzoic acid (DHB). Interestingly, HYNIC displayed remarkable selectivity for ionization of oligosaccharides, making glycans from glycoproteins become more accessible to be detected even without pre-purification, as demonstrated by the direct detection of the oligosaccharides from human serum without pre-separation of the proteins/peptides. The HYNIC matrix also possessed the virtue of higher homogeneity of crystallization and better salt tolerance (up to 200 mM NaCl, 140 mM urea and 40 mM sulfocarbamide et al.) compared with the traditional matrix DHB. Furthermore, the HYNIC matrix afforded adequate fragmentation, thus providing rich information for the structural elucidation of the oligosaccharide. Therefore, using HYNIC as the matrix to directly analyze oligosaccharides is inherently simple and straightforward.
Cross-priming amplification (CPA) was evaluated for the early detection of norovirus (NV), rotavirus A(RV-A), enteric adenovirus (EAdV), and astrovirus (AstV). The analytical sensitivity of the CPA assay was 10(3) copies ml(-1) for NV, RV-A, and AstV detection, and 10(4) copies ml(-1) for EAdV detection. For each of the four pathogens, the positive detection rate by CPA was similar to real time PCR methods and higher than the rate observed in an ELISA assay. The detection coincidence rates of CPA and RT-PCR for NV, RV-A, EAdV, and AstV were 98%, 99%, 99%, and 100% respectively. All CPA assays were negative in 89 healthy control samples. These results demonstrate the high analytical sensitivity and specificity of the CPA assay. CPA assays are relatively straightforward to perform, and such assays represent a potential detection method for locations in which resources are limited. This article is protected by copyright. All rights reserved.
This paper reports one case of atypical falciparum malaria imported from Africa, whose blood smear contains many large trophozoites, with punctiform or massive brown pigment granules, the body shape of the plasmodium is similar to that of Plasmodium vivax and Plasmodium ovale. After the gene detection by PCR, the case was diagnosed as falciparum malaria. As large trophozoites were rarely seen in the peripheral blood of non-severe falciparum malaria cases, much attention should be paid to the identification of Plasmodium falciparum and other plasmodia in microscopic examinations.
Enzymes involved in collagen biosynthesis, including lysyl oxidase (LOX), have been proposed as potential therapeutic targets for idiopathic pulmonary fibrosis. LOX expression is significantly upregulated in bleomycin (BLM)-induced lung fibrosis, and knockdown of LOX expression or inhibition of LOX activity alleviates the lung fibrosis. Unexpectedly, treatment of the mice with LOX inhibitor at the inflammatory stage, but not the fibrogenic stage, efficiently reduces collagen deposition and normalizes lung architecture. Inhibition of LOX impairs inflammatory cell infiltration, TGF-? signaling, and myofibroblast accumulation. Furthermore, ectopic expression of LOX sensitizes the fibrosis-resistant Balb/c mice to BLM-induced inflammation and lung fibrosis. These results suggest that LOX is indispensable for the progression of BLM-induced experimental lung fibrosis by aggravating the inflammatory response and subsequent fibrosis process after lung injury.
Objectives: The aim of this study is to compare preoperative and postoperative conditions of GMP-140 concentration, the aggregation and activation of platelet in congenital heart disease patients undergoing transcatheter closure of atrial septal defects (ASDs) or ventricular septal defects (VSDs), and the appropriate dose of aspirin of patients after transcatheter closure. Materials and Methods: Thirty-two consecutive patients with ASD (n=16) and VSD (n=16), as shown on transthoracic echocardiography and right heart catheter examination, were treated with a percutaneous catheter occlusion. The patients comprised 13 males and 19 females with a mean age of 25.6±9.15. Patients were randomly assigned into two groups within half an hour after ASD or VSD occlusion. Group A cases were treated with 3?mg/kg/day enteric-coated aspirin tablets for 6 months, while patients in group B received 5?mg/kg/day enteric-coated aspirin tablets for 6 months. Results: The rates of platelet aggregation (PAG) in the immediate postoperative ASD/VSD occlusion were significantly higher than those in the preoperative ASD/VSD occlusion (adenosine diphosphate [ADP]-induced PAG: 64.98%±7.65% vs. 86.33%±6.54%, p<0.05; arachidonic acid [AA]-induced PAG: 62.92%±9.11% vs. 86.96%±6.90%, p<0.05, respectively). After treatment with aspirin, the GMP-140 levels presented a clearly defined downward trend in the immediate postoperative period (3?mg/kg/day aspirin: 18.30±3.42 vs. 13.37±1.80, p<0.05; 5?mg/kg/day aspirin: 18.30±3.42 vs. 13.41±1.60, p<0.05), but no obvious difference was observed considering the GMP-140 levels in the 4 days after occlusion (all p>0.05). Conclusion: Our study showed that the GMP-140 serum level and PAG were increased after ASD and VSD occlusion, and patients may have a trend of decreased GMP-140 serum levels after the ASD or VSD occlusion surgeries after the treatment with aspirin. Daily oral administration of 3 and 5?mg/kg/day aspirin can induce a significant decrease in PAG of patients after VSD/ASD occlusion.
In this paper, dispersion properties and field distributions of surface magneto plasmons (SMPs) in double-layer graphene structures at room temperature are studied. It is found that, the dispersion curves of both symmetric and antisymmetric SMPs modes split into several branches/bands when a magnetic field is applied perpendicularly to the graphene surface. Surprisingly, the lowest energy SMP band has anomalous dependence on the applied magnetic field, different to the other higher bands. In addition, the symmetric and antisymmetric modes can be decoupled if the two graphene layers possess different properties, such as different Fermi energies. Furthermore, electric components of the surface modes which are parallel to the graphene surfaces but perpendicular to the propagation direction (i.e. the transverse-electric mode) are no longer zero caused by the Lorentz force on the free electrons.
Ulcerative colitis (UC) is a major form of inflammatory bowel disease (IBD) and increases the risk of the development of colorectal carcinoma. The anti-inflammatory and immunomodulatory properties of mesenchymal stem cells (MSCs) make them promising tools for treating immune-mediated and inflammatory diseases. However, the lack of robust technique for harvesting and expanding of MSCs has hampered the use of bone marrow and umbilical cord blood derived MSCs in clinical applications. In the present study, we investigated the intestinal protective effects of Wharton's jelly derived umbilical MSCs (UMSCs) on dextran sulfate sodium (DSS) induced colitis in mice. The severity of colitis in mice was assessed using body weight loss, stool consistency, rectal bleeding, colon shortening, and hematological parameters. Colonic myeloperoxidase (MPO) and proinflammatory cytokines levels were also measured. Furthermore, the expression of cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) in the colon were detected. In addition, intestinal permeability and tight junction proteins expressions in the colon were examined as well. The results showed that Wharton's jelly derived UMSCs significantly diminished the severity of colitis, reduced histolopathological score, and decreased MPO activity and cytokines levels. Furthermore, the UMSCs markedly decreased the expression of COX2 and iNOS in the colon. In addition, transplantation of UMSCs reduced intestinal permeability and up-regulated the expression of tight junction proteins. These results indicate the anti-inflammation and regulation of tight junction proteins by Wharton's jelly derived UMSCs ameliorates colitis. This article is protected by copyright. All rights reserved.
To assess the association between the serotonin transporter linked polymorphic region (5-HTTLPR) 44 bp variable number of tandem repeat (VNTR) polymorphism and Tourette syndrome (TS) in ethnic Han Chinese trios.
Cephalosporins constitute a large class of ?-lactam antibiotics clinically used as antimicrobial drugs. New Dehli metallo-?-lactamase (NDM-1) poses a global threat to human health as it confers on bacterial pathogen resistance to almost all ?-lactams, including penicillins, cephalosporins, and carbapenems. Here we report the first crystal structures of NDM-1 in complex with cefuroxime and cephalexin, as well as NMR spectra monitoring cefuroxime and cefixime hydrolysis catalyzed by NDM-1. Surprisingly, cephalosporoate intermediates were captured in both crystal structures determined at 1.3 and 2.0 Å. These results provide detailed information concerning the mechanism and pathways of cephalosporin hydrolysis. We also present the crystal structure and enzyme assays of a D124N mutant, which reveals that D124 most likely plays a more structural than catalytic role.
Here we report on the synthesis of novel dendritic Pt3Cu triangular pyramid caps via a solvothermal coreduction method. These caps had three-dimensional caved structures with ultrathin branches, as evidenced by high-resolution transmission electron microscopy (HRTEM) and HAADF-STEM characterization. Tuning the reduction kinetics of two metal precursors by an iodide ion was believed to be the key for the formation of an alloyed nanostructure. Electro-oxidation of methanol and formic acid showed dramatically improved electrocatalytic activities and poison-tolerance for these nanoalloys as compared to commercial Pt/C catalysts, which was attributed to their unique open porous structure with interconnected network, ultrahigh surface areas, as well as synergetic effect of the two metallic components.
In order to get higher vertical resolution atmosphere profile information, the present paper retrieves atmospheric temperature and moisture profiles from the Cross-track Infrared Sounder (CrIS) on the newly-launched Suomi National Polar-orbiting Partnership (Suomi NPP) and future Joint Polar Satellite System (JPSS) with a nonlinear Newton iteration method by using the profiles retrieved via statical regression method as the first guess, and the issue of channel selection is discussed. The retrieved profiles are compared with radiosonde observations, and National Centers for Environmental Prediction (NCEP) Global Data Assimilation System (GDAS) analyses show that the physical retrievals of temperature and moisture are in good agreement with the distributions from GDAS analysis fields and radiosonde observations, and have a notable improvements of the atmospheric profile retrieval accuracy as compared with the eigenvector regression algorithm. For pressures between 200 and 700 hPa the accuracy is of the order of 1 K for the temperature profile, and 20% for the relative humidity profile is consistent with the jacobian peaks of the selected channels.
An analytical method for the determination of urinary cotinine of children exposed to passive smoking was established based on stable isotope dilution by gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS). The samples were extracted and purified with chloroform. The extracts were determined by GC-MS/MS in multiple reaction monitoring (MRM) mode. The cotinine-d3 as an isotope internal standard was applied to quantify and confirm the urinary cotinine of children exposed to passive smoking. The method had a good linearity from 0.1 microg/L to 10 microg/L with the correlation coefficient (r) > 0.998. The recoveries of the cotinine in blank urine were from 79.2% to 112.8% at spiked levels of 0.1, 1.0 and 10 microg/ L, with relative standard deviations (RSDs) from 2.1% to 5. 8%. The limit of quantification ( LOQ) of the method was 0.1 microg/L. The developed method is accurate, sensitive, rapid and can be applied to detect urinary cotinine of children exposed to passive smoking at home.
The World Health Organization (WHO) targeted China for measles elimination by 2012. While China made significant progress, transmission continues, warranting examination of China's measles vaccination program. The WHO recommends that children receive at least two doses of a measles containing vaccine (MCV) to ensure protection. In Tianjin, China, MCV is given in three doses; 8 months (MV), 18-24 months (MMR-1), and 5 years (MMR-2). MMR-2 is important because of the young age for MV administration. This study describes MCV coverage, assesses administration timeliness, and evaluates completion of the MCV series for children living in Tianjin, China.
An analytical method based on solid-phase extraction with single-walled carbon nanotubes (SWCNTs) as adsorbent was developed for the simultaneous determination of six phthalate acid esters (PAEs) in camellia oil by gas chromatography-mass spectrometry (GC-MS). The samples were diluted by hexane and then cleaned up with a glass SWCNTs solid phase extraction (SPE) column. The PAEs were measured by GC-MS in selected ion monitoring (SIM) mode, using external standard method for quantitative analysis. The important factors affecting extraction efficiency, such as the dilution volume of hexane, the type of adsorbent material, the dosage of SWCNTs, the volume of wash solution, the type and volume of elution solution were optimized. The optimal conditions were as follows: the dilution volume of hexane was 5 mL, the dosage of SWCNTs was 0.6 g, the wash solution was 20 mL hexane, and the elution solution was 5 mL toluene. The six PAEs had a good linear range from 0.05 mg/L to 1.0 mg/L, with the correlation coefficients (r) all above 0.999 9. The average recoveries of the six targets in spiked camellia oil (from 0.05 mg/kg to 1.0 mg/kg) ranged from 86.4% to 111.7% with the relative standard deviations (RSDs) from 4.2% to 10.4%. The developed method is accurate, quick and suitable for the determination of the six PAEs in camellia oil.
The Fc portion of immunoglobulin G (IgG) recruits complements and its cognate receptors, thereby promoting defensive mechanisms in the humoral immune system. These effector functions critically depend on N-glycosylation at the Fc region, which is therefore regarded as a crucial factor in the design and production of therapeutic antibodies. NMR spectroscopy plays a unique role in the characterization of conformational dynamics and intermolecular interactions of IgG-Fc in solutions. Here, we report NMR assignments of the glycosylated Fc fragment (Mr 53 kDa), cleaved from a chimeric antibody with human IgG1 constant regions, which was produced in Chinese hamster ovary cells with uniform (13)C- and (15)N-labeling.
To identify the enterovirus from stool samples of patients with hand, foot and mouth disease(HFMD) in Guangzhou from 2010 to 2012 and to perform phylogenetic analysis of the VP1 gene sequences of coxsackievirus A4 and coxsackievirus A10.
The Chinese compound Kaixin Jieyu Fang can be used to treat vascular depression; however, the underlying mechanism remains unclear. This study established a rat model of chronic cerebral ischemia-caused white matter damage by ligation of the bilateral common carotid arteries. Rats received daily intragastric administration of a suspension of Kaixin Jieyu Fang powder. After 3, 7 and 21 days of treatment, the degree of white matter damage in the cerebral ischemia rat model was alleviated, Bcl-2 protein and mRNA expression in brain tissue increased, and Bax protein and mRNA expression decreased. These results indicate that Kaixin Jieyu Fang can alleviate cerebral white matter damage, and the underlying mechanism is associated with regulation of Bcl-2/Bax protein and mRNA expression, which is one of possible mechanism behind the protective effect of Kaixin Jieyu Fang against vascular depression.
Employing a thermodynamic model with previously calculated first-principle energetics as inputs, we determined the hydrogen (H) concentration at the interstitial and monovacancy as well as its dependence on temperature and pressure in tungsten and molybdenum. Based on this, we predicted the critical H concentration for H bubble formation at different temperatures. The critical concentration, defined as the value when the concentration of H at a certain mH-vacancy complex first became equal to that of H at the interstitial, was 24?ppm/7.3 GPa and 410?ppm/4.7 GPa at 600?K in tungsten and molybdenum in the case of a monovacancy. Beyond the critical H concentration, numerous H atoms accumulated in the monovacancy, leading to the formation and rapid growth of H-vacancy complexes, which was considered the preliminary stage of H bubble formation. We expect that the proposed approach will be generally used to determine the critical H concentration for H bubble formation in metals.
A recent advance in scene categorization prefers a topological based modeling to capture the existence and relationships among different scene components. To that effect, local features are typically used to handle photographing variances such as occlusions and clutters. However, in many cases, the local features alone cannot well capture the scene semantics since they are extracted from tiny regions (e.g., 4×4 patches) within an image. In this paper, we mine a discriminative topology and a low-redundant topology from the local descriptors under a probabilistic perspective, which are further integrated into a boosting framework for scene categorization. In particular, by decomposing a scene image into basic components, a graphlet model is used to describe their spatial interactions. Accordingly, scene categorization is formulated as an intergraphlet matching problem. The above procedure is further accelerated by introducing a probabilistic based representative topology selection scheme that makes the pairwise graphlet comparison trackable despite their exponentially increasing volumes. The selected graphlets are highly discriminative and independent, characterizing the topological characteristics of scene images. A weak learner is subsequently trained for each topology, which are boosted together to jointly describe the scene image. In our experiment, the visualized graphlets demonstrate that the mined topological patterns are representative to scene categories, and our proposed method beats state-of-the-art models on five popular scene data sets.
Urinary KIM-1 is an ideal biomarker for acute kidney injury diagnosis. The proof-of-concept is demonstrated by utilizing the hydroxyapatite derived from natural fish scales as an electrode material, where the sensing of KIM-1 is shown to be possible for the first time with a linear range from 0.01 to 0.20 ?g mL(-1) and a detection limit of 0.017 ?g mL(-1) under model conditions; proof-of-concept is demonstrated in spiked urine.
In this study we aimed to screen effective biomarkers for differential diagnosis of ulcerative colitis (UC) and Crohn's disease (CD). By using the gene expression profile dataset GSE24287 including 47 ileal CD, 27 UC and 25 non-inflammatory bowel diseases control downloaded from Gene Expression Omnibus database, we identified the differentially expressed genes (DEGs) between UC patients and controls as well as between CD patients and controls (|log2FC(fold change)| > 1 and p < 0.05). Then Gene Ontology (GO) functional enrichment analyses were performed for these DEGs in two groups, followed by the construction of weight PPI (protein-protein interaction) networks. Subnets enriched for the PPIs and differentially expressed genes were constructed based on the weight PPI networks. The overlapping genes between the genes in the top 10 subnets with smallest p value and the DEGs were selected as the candidate genes of disease. A total of 75 DEGs were identified in UC group and 87 ones in CD group. There were 69 and 57 specific DEGs in CD group and UC group, respectively. The DEGs in CD group were mainly enriched in "inflammatory response" and "defense response", while the most significantly enriched GO terms in UC group were "anion transport" and "chemotaxis". FOS and SOCS3 were identified as candidate genes for CD and other three genes HELB, ZBTB16 and FAM107A were candidate genes for UC. In conclusion, there were distinct genetic alterations between UC and CD. The candidate genes identified in current study may be used as biomarkers for differential diagnosis of CD and UC.
Cse4 is the centromeric histone H3 variant in budding yeast. Psh1 is an E3 ubiquitin ligase that controls Cse4 levels through proteolysis. Here we report that Psh1 is phosphorylated by the Cka2 subunit of casein kinase 2 (CK2) to promote its E3 activity for Cse4. Deletion of CKA2 significantly stabilized Cse4. Consistent with phosphorylation promoting the activity of Psh1, Cse4 was stabilized in a Psh1 phosphodepleted mutant strain in which the major phosphorylation sites were changed to alanines. Phosphorylation of Psh1 did not control Psh1-Cse4 or Psh1-Ubc3(E2) interactions. Although Cse4 was highly stabilized in a cka2? strain, mislocalization of Cse4 was mild, suggesting that Cse4 misincorporation was prevented by the intact Psh1-Cse4 association. Supporting this idea, Psh1 was also stabilized in a cka2? strain. Collectively our data suggest that phosphorylation is crucial in Psh1-assisted control of Cse4 levels and that the Psh1-Cse4 association itself functions to prevent Cse4 misincorporation.
Oral mucositis is one of the most painful side effects found in esophageal squamous cell carcinoma (ESCC) patients treated with chemoradiotherapy. The transdermal route of administration is worthy of investigation for patients who suffer from dysphagia due to severe oral mucositis. In this phase 2 study, we investigated the efficacy and safety of transdermal fentanyl (TDF) for mucositis pain caused by chemoradiotherapy in ESCC patients.
RNA viruses have been associated with enteritis in poultry and have been isolated from diseased birds. The same viral agents have also been detected in healthy flocks bringing into question their role in health and disease. In order to understand better eukaryotic viruses in the gut, this project focused on evaluating alternative methods to purify and concentrate viral particles, which do not involve the use of density gradients, for generating viral metagenome data. In this study, the sequence outcomes of three tissue processing methods have been evaluated and a data analysis pipeline has been established for RNA viruses from the gastrointestinal tract. In addition, with the use of the best method and increased sequencing depth, a glimpse of the RNA viral community in the gastrointestinal tract of a clinically normal 5-week old turkey is presented. The viruses from the Reoviridae and Astroviridae families together accounted for 76.3% of total viruses identified. The rarefaction curve at the species level further indicated that majority of the species diversity was included with the increased sequencing depth, implying that viruses from other viral families were present in very low abundance.
Hand, foot and mouth disease (HFMD) is usually caused by Enterovirus 71(EV71), and Coxsackievirus A16 (CV-A16) in Guangzhou, the biggest city of South China. However, Coxsackievirus A6 (CV-A6) were observed increased dramatically from 2010-2012.
Nanostructured lipid carriers (NLC), composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. The aim of this study was to develop surface-modified NLC as multifunctional nanomedicine for codelivery of enhanced green fluorescence protein plasmid (pEGFP) and doxorubicin (DOX).
Leprosy is the disabling outcome of chronic infection with Mycobacterium leprae. The disease often evades early detection, particularly now that fewer clinicians are able to confidently diagnose the disease following the integration of leprosy control measures within general health services in many countries. Although leprosy is officially eliminated in China, endemic regions remain in some difficult-to-reach, underdeveloped areas in Southwest China. In order to better understand the extent of M. leprae infection and identify new leprosy cases in a timely manner, simple tools that can detect infection and the early disease are required. In this report we evaluated the performance of antigen-specific ELISA, the NDO-LID rapid diagnostic test, and antigen-specific whole blood assays (WBA) as potential diagnostic tools. Our data support the use of antibody detection tests and WBA to facilitate the diagnosis of multibacillary and paucibacillary leprosy, respectively. These tools could be invaluable for increased, but simplified, monitoring of individuals in order to provide referrals for clinical exam and early leprosy diagnosis.
The amphiphilic diblock copolymer composed of methoxy poly(ethylene glycol) and racemic oligoleucine was synthesized which formed into micelle with uniform size in aqueous environment. Doxorubicin (DOX) was loaded into micelle aided by noncovalent interactions with high drug loading efficiency. The DOX-loaded micelle (referred as M-DOX) demonstrated the sustained drug release in vitro and excellent antiproliferative capability toward both MG63 and Saos-2 cells. Furthermore, for both MG63 and Saos-2-xenografted BALB/c nude mouse models, M-DOX exhibited enhanced intratumoral distribution, improved antitumor efficacy, and reduced side effects compared with free DOX. Therefore, the polypeptide micelle showed a bright prospect for controlled delivery of antitumor drugs in vivo.
The objective of this study was to explore the relationship between single-nucleotide polymorphisms (SNPs) of the protein kinase C gamma (PRKCG) gene and osteosarcoma susceptibility in Chinese Han population. A total of 610 cases of osteosarcoma patients and 610 healthy individuals were enrolled in this study. TaqMan method was used to compare genotypes and the allelic distribution frequency of three SNPs (rs454006, rs2242245, and rs8103851) in the PRKGG gene between osteosarcoma patients and healthy individuals. Osteosarcoma patients were grouped according to different clinical parameters (age, gender, pathological types, tumor location, Enneking staging, tumor metastasis and treatment) to compare genotype and allele frequency among different groups as well as to explore the relationship between gene polymorphisms and different clinical parameters. The rs454006 polymorphisms of the PRKCG gene include the CC, CT, and TT genotypes. The differences in genotype frequency and allele frequency between osteosarcoma patients and healthy individuals were significant (both P?0.001). There was no significant different between osteosarcoma patients and healthy individuals in rs8103851 and rs2242245 polymorphisms of the PRKCG gene (both P?>?0.05). The differences of the rs8103851 genotype frequency and allele frequency in patients with metastatic osteosarcoma and patients without metastasis were significant (both P?0.001). The distribution frequencies of the CG and GG genotypes as well as the G allele in patients with metastatic osteosarcoma were higher than in patients without metastasis. The genotype frequency and allele frequency of rs454006 and rs2242245 did not correlate with clinical parameters. The rs454006 polymorphism of the PRKCG gene correlated to osteosarcoma susceptibility and might increase the risk of osteosarcoma. The rs8103851 correlated to metastatic osteosarcoma and could be risk factors for metastatic osteosarcoma.
We report planar integration of tapered terahertz (THz) frequency quantum cascade lasers (QCLs) with metasurface waveguides that are designed to be spoof surface plasmon (SSP) out-couplers by introducing periodically arranged SSP scatterers. The resulting surface-emitting THz beam profile is highly collimated with a divergence as narrow as ~4° × 10°, which indicates a good waveguiding property of the metasurface waveguide. In addition, the low background THz power implies a high coupling efficiency for the THz radiation from the laser cavity to the metasurface structure. Furthermore, since all the structures are in-plane, this scheme provides a promising platform where well-established surface plasmon/metasurface techniques can be employed to engineer the emitted beam of THz QCLs controllably and flexibly. More importantly, an integrated active THz photonic circuit for sensing and communication applications could be constructed by incorporating other optoelectronic devices such as Schottky diode THz mixers, and graphene modulators and photodetectors.
Cell microencapsulation technology is a potential alternative therapy, but cell overgrowth and adhesion on the microcapsules after transplantation shortens their time of therapeutic efficacy. Inflammatory cells were the main cells that adhered to the microcapsules, so understanding the body's inflammatory processes would help to better identify the mechanisms of cell adhesion to the outer surface of the microcapsules. Our study measured the inflammatory cells and the cytokines and characterized the associated changes in the alginate-chitosan-alginate (ACA) microcapsules 1, 7, 14, and 28 days after implantation in the peritoneal cavity. Then the relationship between the inflammatory response and cell adhesion on the microcapsules was evaluated by multiple regression analysis. The results showed that the microcapsules did not evoke a systemic inflammatory response, but initiated a local inflammatory response in the peritoneal cavity. Furthermore, the correlation analysis showed that the level of cell adhesion on the microcapsules was related to the number of lymphocytes and macrophages, and the amount of IL-6, IL-10, and MCP-1 in the peritoneal cavity. Our results may provide a foundation for reducing the immune response to these microcapsules, prolonging graft survival and improving the efficacy of these treatments. This article is protected by copyright. All rights reserved.
Chronic inflammation is one of the main symptoms of cancer cachexia, and cyclooxygenase 2 inhibitors, such as celecoxib, may be beneficial in counteracting the major symptoms of this syndrome. In the current study, celecoxib was orally administered to BALB/c male mice with colon 26 adenocarcinoma. Tumor growth, survival rate, body weight and food intake of the mice with cancer cachexia were recorded during the experiments. The host inflammatory response was assessed by morphological observations and hematoxylin?eosin staining. The serum levels of vascular endothelial growth factor (VEGF), granulocyte?macrophage colony?stimulating factor, interleukin?6 and tumor necrosis factor?? in mice with cancer cachexia were measured by ELISA. Celecoxib administration attenuated the decline in body weight and food intake of mice with cancer cachexia, and improved the survival rate of cachectic mice. Erythrocyte counts and hemoglobin concentration significantly increased in cachectic mice receiving celecoxib compared with control cachectic mice. Notably, celecoxib administration significantly reduced the serum level of VEGF in mice with colon 26 adenocarcinoma, and the cachectic events were also relieved by treatment with a VEGF antibody. The cyclooxygenase 2 inhibitor celecoxib produced positive therapeutic effects in mice with cancer cachexia. This function was regulated at least partly by downregulation of serum levels of VEGF.
This study utilizes the unique merits of an 8-L laboratory upflow anaerobic sludge blanket (UASB) reactor for treating synthetic wastewater containing trichloroethylene (TCE). The reactor was operated at different hydraulic retention times (HRT) of 25, 20, 15, 10, and 5 h. TCE removal efficiency decreased from 99 to 85 % when the HRT was lowered down from 25 to 5 h, as well as chemical oxygen demand (COD) removal efficiency (from 95 to 84.15 %). Using Illumina 16S rRNA gene MiSeq sequencing, we investigated the evolution of bacterial communities in the anaerobic sludge under five different conditions of HRT. In total, 106,387 effective sequences of the 16S rRNA gene were generated from 5 samples that widely represented the diversity of microbial community. Sequence analysis consisting of several novel taxonomic levels ranging from phyla to genera revealed the percentages of these bacterial groups in each sample under different HRTs. The differences found among the five samples indicated that HRT had effects on the structures of bacterial communities and the changes of bacterial communities associated with the effect of HRT on the performance of the reactor. Sequence analyses showed that Bacteroidetes and Firmicutes were the dominant phyla. It is notable that the class Dehalococcoidia was found in the samples at HRT of 5, 10, 20, and 25 h, respectively, in which there were some dechlorination strains. Moreover, a tremendous rise of TCE removal efficiency from HRT of 5 h to HRT of 10 h was found.
Two kinds of triblock poly(ethylene glycol)-polyleucine (PEG-PLeu) copolymers were synthesized through the ring-opening polymerization of l-Leu N-carboxyanhydride (NCA), or equivalent d-Leu NCA and l-Leu NCA with amino-terminated PEG as a macroinitiator. The amphiphilic copolymers spontaneously self-assembled into spherical micellar aggregations in an aqueous environment. The micelle with a racemic polypeptide core exhibited smaller critical micelle concentration and diameter compared to those with a levorotatory polypeptide core. A model anthracycline antineoplastic agent, i.e., doxorubicin (DOX), was loaded into micelles through nanoprecipitation, and the PEG-P(d,l-Leu) micelle exhibited higher drug-loading efficacy than that with a P(l-Leu) core-this difference was attributed to the flexible and compact P(l-Leu) core. Sustained in vitro DOX release from micelles with both levorotatory and racemic polypeptide cores was observed, and the DOX-loaded PEG-P(d,l-Leu) micelle exhibited a slower release rate. More interestingly, DOX-loaded micelles exhibited chirality-mediated antitumor efficacy in vitro and in vivo, which are all better than that of free DOX. Furthermore, both enhanced tumor inhibition and excellent security in vivo were confirmed by histopathological or in situ cell apoptosis analyses. Therefore, DOX-loaded PEG-PLeu micelles appear to be an interesting nanoscale polymeric formulation for promising malignancy chemotherapy.
The ability to engineer the surface properties of magnetic nanoparticles is important for their various applications, as numerous physical and chemical properties of nanoscale materials are seriously affected by the chemical constitution of their surfaces. For some specific applications, nanoparticles need to be transferred from a polar to a nonpolar environment (or vice versa) after synthesis. In this work we have developed a universal method for the phase transfer of magnetic nanoparticles that preserves their shape and size. Octadecyltrimethoxysilane was used to cap the surfaces of the aqueous magnetic nanoparticles, thereby allowing their transfer into nonpolar solution. The resulting hydrophobic magnetic nanoparticles were transferred back into aqueous solution by subsequently covering them with an egg-PC lipid monolayer. The superparamagnetic properties of the particles were retained after the phase transfer. The maximum transfer yields are dependent on their particle size with a maximum value of 93.16±4.75?% for magnetic nanoparticles with a diameter of 100?nm. The lipid-modified magnetic particles were stable over 1?week, and thus they have potential applications in the field of biomedicine. This work also provides a facile strategy for the controllable engineering of the surface properties of nanoparticles.
Bone marrow mesenchymal stem cells can differentiate into neurons and astrocytes after transplantation in the spinal cord of rats with ischemia/reperfusion injury. Although bone marrow mesenchymal stem cells are known to protect against spinal cord ischemia/reperfusion injury through anti-apoptotic effects, the precise mechanisms remain unclear. In the present study, bone marrow mesenchymal stem cells were cultured and proliferated, then transplanted into rats with ischemia/reperfusion injury via retro-orbital injection. Immunohistochemistry and immunofluorescence with subsequent quantification revealed that the expression of the axonal regeneration marker, growth associated protein-43, and the neuronal marker, microtubule-associated protein 2, significantly increased in rats with bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Furthermore, the expression of the autophagy marker, microtubule-associated protein light chain 3B, and Beclin 1, was significantly reduced in rats with the bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Western blot analysis showed that the expression of growth associated protein-43 and neurofilament-H increased but light chain 3B and Beclin 1 decreased in rats with the bone marrow mesenchymal stem cell transplantation. Our results therefore suggest that bone marrow mesenchymal stem cell transplantation promotes neurite growth and regeneration and prevents autophagy. These responses may likely be mechanisms underlying the protective effect of bone marrow mesenchymal stem cells against spinal cord ischemia/reperfusion injury.
Loss of STAT1 (Signal Transducer and Activator of Transcription-1) has been implicated in the pathobiology of a number of cancer types. Nonetheless, the biological and clinical significance of STAT1 in esophageal squamous cell carcinomas (ESCC) has not been comprehensively studied.
Antioxidant of bamboo leaves (AOB) is a novel natural food antioxidant approved in China since 2004. Natural phenolics contained in the current AOB are usually polyhydroxy derivatives exhibiting hydrophilic character, which has been marked as water-soluble AOB (AOB-w). In order to broaden the application fields, oil-soluble AOB (cAOB-o) was obtained by chemical acylation of AOB-w with different chain-length fatty acids varying from C8 to C18. Results indicated that the yield and solubility of cAOB-o in 1-octanol solvent depended on the carbon chain length of acyl donor, and cAOB-o derived from C12 fatty acid exhibited the more powerful antioxidant activity evaluated by ?-carotene/linoleic acid bleaching assay. Total phenolic content decreased by Folin-Ciocalteu assay. Fourier transform infrared spectra showed the increase of a carbonyl (C = O) peak at 1701 cm(-1) and a decrease in the intensity of the absorption at 3400 cm(-1) (O-H stretching) in cAOB-o. Acylation was inferred to mainly occur on the hydroxyl groups of flavones C-glycosides according to the change of high-performance liquid chromatography spectra and the contents of total flavonoids and phenolic acids. cAOB-o with the addition of 0.02% significantly increased oxidative stability of palm oil 1.59 times, lard 3.74 times, and fried potato chips 2.08 times, which was better than the effect of oil-soluble tea polyphenol (P < 0.01). Moreover, cAOB-o was identified to be actually nontoxicity by an acute oral toxicity test. All the above results indicated that cAOB-o could be used as a novel and effective oil-soluble antioxidant in the food industry.
A novel sequential permeable reactive barrier (multibarrier), composed of oxygen-releasing compound (ORC)/clinoptilolite/spongy iron zones in series, was proposed for ammonium-nitrogen-contaminated groundwater remediation. Column experiments were performed to: (1) evaluate the overall NH4 (+)-N removal performance of the proposed multibarrier, (2) investigate nitrogen transformation in the three zones, (3) determine the reaction front progress, and (4) explore cleanup mechanisms for inorganic nitrogens. The results showed that NH4 (+)-N percent removal by the multibarrier increased up to 90.43 % after 21 pore volumes (PVs) at the influent dissolved oxygen of 0.68?2.45 mg/L and pH of 6.76?7.42. NH4 (+)-N of 4.06?10.49 mg/L was depleted and NO x (-)-N (i.e., NO3 (-)-N?+?NO2 (-)-N) of 4.26?9.63 mg/L was formed before 98 PVs in the ORC zone. NH4 (+)-N of ?4.76 mg/L was eliminated in the clinoptilolite zone. NO x (-)-N of 10.44?12.80 mg/L was lost before 21 PVs in the spongy iron zone. The clinoptilolite zone length should be reduced to 30 cm. Microbial nitrification played a dominant role in NH4 (+)-N removal in the ORC zone. Ion exchange was majorly responsible for NH4 (+)-N elimination in the clinoptilolite zone. Chemical reduction and hydrogenotrophic denitrification both contributed to NO x (-)-N transformation, but the chemical reduction capacity decreased after 21 PVs in the spongy iron.
The endocannabinoids system (ECs) mediated mainly by CB1 and CB2 receptors plays an important role in non-alcoholic fatty liver disease by regulating lipid metabolism. This study is to further investigate the expression of CB1 and CB2 in the fat accumulation liver cells and to identify possible underlying mechanism by detecting the key lipogenesis factors.
Chondrogenesis is a developmental process that is controlled and coordinated by many growth and differentiation factors, in addition to environmental factors that initiate or suppress cellular signaling pathways and the transcription of specific genes in a temporal-spatial manner. As key signaling molecules in regulating cell proliferation, homeostasis and development, both mitogen-activated protein kinases (MAPK) and the Wnt family participate in morphogenesis and tissue patterning, playing important roles in skeletal development, especially chondrogenesis. Recent findings suggest that both signals are also actively involved in arthritis and related diseases. Despite the implication that crosstalk between MAPK and Wnt signaling has a significant function in cancer, few studies have summarized this interaction and its regulation of chondrogenesis. In this review, we focus on MAPK and Wnt signaling, referencing their relationships in various types of cells and particularly to their influence on chondrogenesis and cartilage development. We also discuss the interactions between MAPK and Wnt signaling with respect to cartilage-related diseases such as osteoarthritis and explore potential therapeutic targets for disease treatments.
Several studies have confirmed the role of microRNAs in regulating ischemia/reperfusion-induced cardiac injury (I/R-I). MiR-17-5p has been regarded as an oncomiR in the development of cancer. However, its potential role in cardiomyocytes has not been exploited. The aim of this study is to investigate the role of miR-17-5p in I/R-I and the underlying mechanism through targeting Stat3, a key surviving factor in cardiomyocytes.
Exploration of the conformational spaces of flexible biomacromolecules is essential for quantitatively understanding the energetics of their molecular recognition processes. We employed stable isotope- and lanthanide-assisted NMR approaches in conjunction with replica-exchange molecular dynamics (REMD) simulations to obtain atomic descriptions of the conformational dynamics of high-mannose-type oligosaccharides, which harbor intracellular glycoprotein-fate determinants in their triantennary structures. The experimentally validated REMD simulation provided quantitative views of the dynamic conformational ensembles of the complicated, branched oligosaccharides, and indicated significant expansion of the conformational space upon removal of a terminal mannose residue during the functional glycan-processing pathway.
The AP2 clathrin adaptor complex links protein cargo to the endocytic machinery but it is unclear how AP2 is activated on the plasma membrane. Here we demonstrate that the membrane-associated proteins FCHo and SGIP1 convert AP2 into an open, active conformation. We screened for Caenorhabditis elegans mutants that phenocopy the loss of AP2 subunits and found that AP2 remains inactive in fcho-1 mutants. A subsequent screen for bypass suppressors of fcho-1 nulls identified 71 compensatory mutations in all four AP2 subunits. Using a protease-sensitivity assay we show that these mutations restore the open conformation in vivo. The domain of FCHo that induces this rearrangement is not the F-BAR domain or the µ-homology domain, but rather is an uncharacterized 90 amino acid motif, found in both FCHo and SGIP proteins, that directly binds AP2. Thus, these proteins stabilize nascent endocytic pits by exposing membrane and cargo binding sites on AP2.
Restoration of insulin secretion by transplantation of isolated islets is a treatment for type ? diabetes mellitus. One of the major issues with clinical treatment of islet transplantation is how to maintain islet viability during transportation from the donor to the patient.
A better understanding of public perceptions, attitude and behavior in relation to climate change will provide an important foundation for government?s policy-making, service provider?s guideline development and the engagement of local communities. The purpose of this study was to assess the perception towards climate change, behavior change, mitigation and adaptation measures issued by the central government among the health professionals in the Centres for Disease Control and Prevention (CDC) in China.
Abstract Aim: The aim of this study was to determine the prevalence of autoimmune thyroid disease in Turner syndrome (TS) and the association between thyroid autoantibodies (TAA), thyroid dysfunction, age, and karyotype. Methods: Sixty-nine girls with TS were divided into two groups according to being TAA-positive or TAA-negative. TAA and thyroid hormone concentrations were determined by immunochemiluminescence. Results: One third (23/69) of the girls were TAA positive, with antibody prevalence increasing with age. Of the TAA-positive girls, seven were hypothyroid and three hyperthyroid. Compared with the TAA-negative group, the girls in the TAA-positive group were significantly older (p<0.05). For those who were TAA positive, 26.3% of patients were 5-10 years old, 37.1% 10-15 years old, and 62.5% above the age of 15 years. Conclusion: Chinese girls with TS are prone to Hashimoto's thyroiditis, especially those older than 5 years, and routine thyroid testing is advocated thereafter on a yearly basis. There was no specific association between the incidence of autoimmune thyroid disease and TS karyotypes.
Related JoVE Video
Journal of Visualized Experiments
What is Visualize?
JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.
How does it work?
We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.
Video X seems to be unrelated to Abstract Y...
In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.