A data-mining approach to biomarker identification from protein profiles using discrete stationary wavelet transform

Objective： To develop a new bioinformatic tool based on a data-mining approach for extraction of the most informative proteins that could be used to find the potential biomarkers for the detection of cancer. Methods： Two independent datasets from serum samples of 253 ovarian cancer and 167 breast cancer patients were used. The samples were examined by surfaceenhanced laser desorption/ionization time-of-flight mass spectrometry （SELDI-TOF MS）. The datasets were used to extract the informative proteins using a data-mining method in the discrete stationary wavelet transform domain. As a dimensionality reduction procedure, the hard thresholding method was applied to reduce the number of wavelet coefficients. Also, a distance measure was used to select the most discriminative coefficients. To find the potential biomarkers using the selected wavelet coefficients, we applied the inverse discrete stationary wavelet transform combined with a two-sided t-test. Results： From the ovarian cancer dataset, a set of five proteins were detected as potential biomarkers that could be used to identify the cancer patients from the healthy cases with accuracy, sensitivity, and specificity of 100%. Also, from the breast cancer dataset, a set of eight proteins were found as the potential biomarkers that could separate the healthy cases from the cancer patients with accuracy of 98.26%, sensitivity of 100%, and specificity of 95.6%. Conclusion： The results have shown that the new bioinformatic tool can be used in combination with the high-throughput proteomic data such as SELDI-TOF MS to find the potential biomarkers with high discriminative power.     

SELDI-TOF-MS in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease(COPD) has a profound impact on daily life,yet remains underdiagnosed and undertreated.This study aims to discover potential protein biomarkers for diagnosis and classification of COPD.Fifty-seven COPD patients and 40 controls were divided into a training set(30 COPD patients,20 healthy controls) and a test set(27 COPD patients,20 healthy controls).Serum proteomic profiles were measured using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry(SELDI-TOF-MS).A classification tree was established using Biomarker Pattern Software(BPS).Next we screened distinct proteins present in patients with acute exacerbations of COPD(AECOPD),stable COPD and healthy controls,in order to establish diagnostic models for classification of COPD.Twenty peaks showed statistically significant differences between COPD patients and healthy controls(P < 0.05).Two proteomic peaks(3167 and 5477 m/z) were chosen by BPS to establish a classification tree in the training set.The sensitivity and specificity of this classification tree were 92.59% and 90.00% respectively in the testing set.Furthermore,differently expressed proteins were detected among the patients with AECOPD,stable COPD,and healthy controls.Two protein profiles(3167 and 4645 m/z) could distinguish between stable COPD patients and healthy controls.Three protein profiles(3167,2963 and 2973 m/z) could distinguish between AECOPD patients and healthy controls.Three protein profiles(5476,14039 and 2831 m/z) could distinguish between stable COPD patients and AECOPD patients.SELDI-TOFMS Proteinchip technology is a quick,easy and practical,high throughput analytic method.It shows the diagnostic models established by distinguished proteomic peaks can discriminate COPD patients from healthy control and can identify different stages of COPD.It will provide a highly accurate approach for diagnosis and clinical staging of COPD.     

Nitric oxide:A potential key point of the signaling network leading to plant secondary metabolite biosynthesis

The endogenous signaling network of plants plays important roles in mediating the exogenous factor-induced biosynthesis of secondary metabolites. Nitric oxide (NO) has emerged as a key signaling molecule in plants recently. Numerous studies demonstrated that the main signaling molecules such as salicylic acid (SA), jasmonic acid (JA), reactive oxygen species (ROS), and NO were not only involved in regulating plant secondary metabolite biosynthesis but also interacted to form a complex signaling network by mutual inhibition and/or synergy. The recent progress in the signal network of plant secondary metabolite biosynthesis has been discussed in this paper. Furthermore, we propose a hypothetical model to show that NO might act as a potential molecular switch in the signaling network leading to plant secondary metabolite biosynthesis.     

Sodium arsenite reduces severity of dextran sulfate sodium-induced ulcerative colitis in rats

The histopathological features and the associated clinical findings of ulcerative colitis （UC） are due to persistent inflammatory response in the colon mucosa. Interventions that suppress this response benefit UC patients. We tested whether sodium arsenite （SA） benefits rats with dextran sulfate sodium （DSS）-colitis. The DSS-colitis was induced by 5% DSS in drinking water. SA （10 mg/kg; intraperitoneally） was given 8 h before DSS treatment and then every 48 h for 3 cycles of 7, 14 or 21 d. At the end of each cycle rats were sacrificed and colon sections processed for histological examination. DSS induced diarrhea, loose stools, hemoccult positive stools, gross bleeding, loss of body weight, loss of epithelium, crypt damage, depletion of goblet cells and infiltration of inflammatory cells. The severity of these changes increased in the order of Cycles 1, 2 and 3. Treatment of rats with SA significantly reduced this severity and improved the weight gain.     

Glycyrrhetinic acid-modified nanoparticles for drug delivery: Preparation and characterization

In this work, glycyrrhetinic acid-modified chitosan （mGA-suc-CTS） used as liver targeted carrier for drug delivery, was prepared via hemisuccinate as a bridged group. The structure of the product was confirmed by IR and NMR methods and the degree of substitution （DS） of glycyrrhetinic acid groups was estimated via elemental analysis. Nanoparticles were formed by ionic gelation methold. The drug-loading and release behavior of the nanoparticles were investigated using BSA as the model drug. The results indicated that the carrier with a highest DS of 5.19% could be got and the DS was controlled by changing reaction temperature or feed ratio. BSA could be entrapped into the nanoparticles with the drug-loading ratio of 26.3% and the encapsulation efficiency of 81.5%. A sustained release over an 11-day period was observed in pH 7.4 in vitro.     

Oscillating chemiluminescence in rhodamine B-induced Belousov-Zhabotinsky reaction catalyzed by Ce（IV）

It was found that rhodamine B could induce oscillating chemiluminescence （OCL） from the Ce4＋-catalyzed Belousov-Zhabotinsky reaction. This new OCL system, i.e., rhodamine B-malonic acid-bromate- Ce（IV）-sulfuric acid, exhibited two clearly distinguished emission peaks in each oscillation period. The initial concentrations of the reactants strongly influenced the oscillation pattern. For the study of the CL mechanism, a platform for a versatile and simultaneous potential and CL measurement was estab- lished to compare the potential oscillation with the CL oscillation behavior of this system. The CL spectra, UV-visible absorption spectra and time-resolved fluorescence spectra of this OCL system were studied. A possible, simplified mechanism for the OCL is proposed. It is suggested that the generation of the two CL peaks is likely due to the oxidation of the intermediate of rhodamine B by Ce（IV） and Br2, respectively. This work provided a new method and platform to research the complex chemical oscilla- tions.     

Effects of medium nutrition on cell growth and isocamptothecin A and B production by suspension cell culture of Camptotheca acuminata

The effects of initial sucrose concentration, nitrate to ammonium ratio, total N concentration and phosphate concentration in medium on cell growth and isocamptothecin A and B synthesis by suspension call culture of Camptotheca acuminata were investigated in 250 mL shake flasks. 30 g L^-1 sucrose concentration was beneficial to secondary metabolites synthesis. The cell growth and metabolites synthesis were also affected by the ratio of NO3^-/NH4^＋ , and nitrate was tavourable for cell growth. The maximum dry weight was achieved when nitrate was used as the sole N souree. The effect of total initial N on the cell cultures was also investigated with NO3^-/NH4^＋ ratio of 1 ： 2. The final dry cell weight was similar throughout culture period and 50 mM initial N was favourable for secondary metabolite synthesis. 50 mM initial phosphate concentration facilitated both cell growth and secondary metabolites synthesis.     

Removal of disinfection by-product formation potentials by biologically assisted GAC treatment

The object of this paper is to evaluate the removal of disinfection by-products formation potential by artificially intensified biological activated carbon（BAC） process which is developed on the basis of traditional ozone granular activated carbon （GAC）. The results show that 23.1% of trihalomethane formation potential （THMFP） and 68% of haloacetic acid formation potential （HAAFP） can be removed by BAC, respectively. Under the same conditions, the removal rates of the same substances were 12.2% and 13-25% respectively only by GAC process. Compared with GAC, the high removal rates of the two formed potential substances were due to the increasing of bioactivity of the media and the synergistic capabilities of biological degradation cooperating with activated carbon adsorption of organic compounds. BAC process has some advantages such as long backwashing cycle time, low backwashing intensity and prolonged activated carbon lifetime, etc.     

Effects of helium on titanium films and the helium diffusion

Using direct current-magnetron sputtering, Helium-trapped Ti films with a He/Ar mixture was studied. The relative helium content, helium depth profiles for the Ti films and crystallization capacity were analyzed by Enhanced Proton Backscattering Spectrometry （EPBS） and X-ray diffraction （XRD）. It was found that helium diffusion enhanced as more helium trapping into Ti films, and the He holding ratios were 95.9%, 94.9%, 93.9%, 82.8% when the Ti films with the He/Ti of concentrations of 9.7 at.%, 19.5 at.%, 19.7 at.%, 48.3 at.% were measured again 4 months later, respectively. The diffraction peaks became weak and wider, the peak of （002） plane was shifted to smaller diffraction angles and the relevant interplanar spacing d（hk,） increased gradually as more helium trapping into Ti films. The main peak was made trending to the （101） plane by both higher deposition temperature and more helium trapping.     

Proteiomic patterns for endometrial cancer using SELDI-TOF-MS

Serum samples from endometrial cancer （EC） patients and healthy females were analyzed using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry （SELDI-TOF-MS） to discover the potential diagnostic biomarker for detection of EC. A preliminary training set of spectra derived from 40 E C patients and 30 healthy women were used to develop a proteomic model that effectively discriminated cancer patients from healthy women. The training set had a specificity of 100% and sensitivity of 92.5% in the EC detection. A blind test set, including 20 new cancer cases and 10 healthy women, was used to validate the sensitivity and specificity of this multivariate model, which had a corresponding results of 60% in specificity and 75% in sensitivity, respectively. The combination of SELDI-TOF-MS with bioinformatics tools could help find new biomarkers and establish the detection of EC with high sensitivity and specificity.     

Values of endoscopic ultrasonography for diagnosis and treatment of duodenal protruding lesions

Objective： The diagnoses of patients with duodenal protruding lesions are difficult when using conventional examinations such as computed tomography （CT） and conventional endoscope etc. Thus, we investigated the clinical value of endoscopic ultrasonography （PUS） with miniature ultrasonic probes on the diagnosis and treatment of duodenal protruding lesions. Methods： Patients with duodenal protruding lesions who were indicated for PUS were examined by PUS with 12-15 MHz miniature ultrasonic probes and double-cavity electronic endoscope. According to diagnosis of PUS, those patients were indicated for biopsy and treatment received biopsy, endoscopic resection or surgical excision. The postoperative histological results were compared with the preoperative diagnosis of PUS. Those patients without endoscopic resection or surgical excision were periodically followed up with PUS. Results： A total of 169 patients with duodenal protruding lesions were examined by PUS, of which 40 were diagnosed with cysts, 36 with inflammatory protruding or polyp, 25 with Brunner＇s gland adenoma, 19 with ectopic pancreas, 17 with gastrointestinal stromal tumor, 12 with extrinsic compression, 12 with minor papilla, 6 with lipoma, 1 with adenocarcinoma and 1 with lymphoma. After PUS examinations, 75 patients received biopsy, endoscopic resection or surgical excision respectively. The postoperative histological results of 70 patients were completely consistent with the preoperative diagnosis of PUS, with 93.33% diagnostic accuracy. The results of follow-up with PUS indicated that duodenal cyst, Brunner＇s gland adenoma, ectopic pancreas, gastrointestinal stromal tumor and lipoma remained unchanged within 1-3 years. No related complications occurred among all patients that received PUS examinations. Conclusion： PUS is an effective and reliable diagnostic method for duodenal protruding lesions.     

Immobilization of biomacromolecules on poly-L-lactide surface via a layer-by-layer method for the improving of its cytocompatibility to bone marrow stromal cells

Hyaluronic acid （HA） and chitosan （CS） were immobilized on the surface of poly-L-lactide （PLLA） by the following procedure： Firstly, PLLA was aminolyzed with 1, 6-hexanediamine, and part of the PLLA surface ester groups were converted to free amino groups. Then negatively charged hyaluronic acid and positively charged chitosan were deposited onto the surface of aminolyzed PLLA film in a layer-by-layer assembly manner. The effect of the layer-by- layer deposition was evaluated by ATRoFTIR spectroscopy, Raman spectroscopy and static contact angle measurements. The cytocompatibility of PLLA sample to bone marrow stromal cells （BMSCs） was improved after modification with chitosan and HA. The cell attachment, activity, and proliferation on CS/HA modified PLLA films were enhanced comparing with the control. The cells cultured on the modified PLLA samples excreted abundant cytoplasm and can differentiate to vascular smooth muscle （SM）-like （SM-like） cells. A macroporous three-dimensional PLLA scaffold was prepared by integrating both the technique of freeze-drying and particle leaching. Layer-by-layer modification by HA/CS and cell culture was also applied on this scaffold. The scaffold cultured with BMSCs for 2 weeks has been tested successfully in vivo as a patch for repairing the artificial incision on canine pulmonary artery.     

A ballistocardiogram measurement system for home monitoring: design,performance, and evaluation

We present a ballistocardiogram （BCG） measurement system for obtaining the BCG signal. The performance of the BCG measurement system was tested, including the dynamic response frequency of the platform （32 Hz with a 75 kg load）, and the signal to noise ratio of the system （minimum 23 dB）. Factors that could influence BCG recording during measurement were investigated by collecting data from 48 healthy subjects （28 males and 20 females）. The basic features of the BCG signal, such as the amplitude and time interval, were extracted, and differences by gender were analyzed. A correlation between the IJ amplitude （amplitude difference between I-and J-peak） and the respiration phase was found （R2 = 0.49）. The BCG signals for both sitting （SiBCG） and standing （StBCG） postures were obtained using this system. These showed that the StBCG amplitudes were larger than those of SiB- CG but there was no significant difference in the time intervals. The robustness of our system was verified, and its potential for noninvasive cardiac activity monitoring was demonstrated.     

Hypothetical mode of action of earthworm extract with hepatoprotective and antioxidant properties

The hepatoprotective potential of earthworm extract （EE） （Lampito mauritii, Kinberg） was evaluated against paracetamol-induced liver injury in Wistar albino rat, in comparison with silymarin, the standard hepatoprotective drug. We observed a reduction in liver antioxidants, such as glutathione （GSH）, superoxide dismutase （SOD）, glutathione peroxidase （GPx）, and catalase （CAT） and in serum total protein, and an increase in serum alkaline phosphatase （ALP）, serum aspertate ami- notranferase （AST）, serum alanine aminotranferase （ALT）, bilirubin and liver thiobarbituric acid reactive substances （TBARS） due to liver injury in the paracetamol-administered rats （2 g/kg）. On the contrary, increased activities of liver GSH, SOD, GPx, CAT and serum total protein level, and decrease in the contents of serum ALP, AST, ALT, bilirubin and liver TBARS were observed in rats administered with different doses of EE （100, 200 and 300 mg/kg）, which are similar to the activities of hepato- protective drug silymarin （150 mg/kg）. The mode of action of EE as evidenced by the above parameters may suggest that EE, on the one hand, prevents the formation of the reactive oxygen groups, or scavenges these groups, thereby preventing the damage on the hepatic cells, and, on the other hand, modulates the genes responsible for synthesis of antioxidant enzymes such as GPx, CAT and SOD in liver tissue and decreases the serum enzymatic activities such as ALP, AST and ALT.     

Enhancing Phosphorous Recovery in a Novel Biofilter System

Developing new techniques to remove and recover phosphorous simultaneously from wastewaters is very important for sustainable utilization of phosphorous resource and prevention of eutrophication. The feasibility of phosphorus bioaccumulation in a novel continuous alternating anaerobic /aerobic biofilter and benefits of such accumulation for its further recovery as magnesium ammonia phosphate （MAP） were studied. The system was operated for seven months and employed the atomic absorption spectrophotometer （AAS） method to analyze the distribution change of magnesium and calcium with phosphate in the biofilter during that period. The benefits of utilizing the biofilter system to accumulate phosphorous ＆ magnesium and suppress calcium simultaneously to phosphorous recovery as MAP were explained with the aid of chemical equilibrium models. The improved phosphorus recovery from 42% to 82% was approved in the recovery experiments and the recovery products mainly as MAP were evidenced and characterized with scanning electron microscopy （SEM） . The study provides references for designing and operating the novel alternating anaerobic /aerobic biofilter for phosphorus bioaccumulation and recovery.     

Serum microRNA-155 as a potential biomarker for breast cancer screening

MicroRNAs(miRs) have been shown to be differentially expressed in the serum of cancer patients and controls,and can thus be used as biomarkers for cancer screening.We detected the expression level of miR-155 in the serum of female breast cancer patients and healthy controls to investigate whether serum miR-155 could discriminate patients with early-stage breast cancer.Serum samples were collected from 20 female patients with newly diagnosed breast cancer and 10 healthy controls.Real-time quantitative PCR was used to detect the expression level of miR-155.The expression level of miR-155 was significantly increased in the serum of breast cancer patients compared with in the serum of normal controls.MiR-155 may be useful as a blood-based biomarker for breast cancer screening.     

Utilizing Water Treatment Residuals for Phosphorus Removal: Batch Trials,Column Trials and Effects of Three Low-Molecular-Weight Organic Acids

Phosphorus（ P） has been recognized as a major limited nutrient responsible for the eutrophication of surface waters. Water treatment residuals（ WTRs） are safe by-products of water treatment plants and are cost-efficient adsorbents. In this study, batch experiments and column experiments based on WTRs were employed to study the characteristics of P adsorption and the effects of lowmolecular-weight organic acids（ LMWOAs）（ citric acid, oxalic acid,and tartaric acid） on P adsorption. Different models of adsorption were used to describe equilibrium and kinetic data. The adsorption data were fitted well by a pseudo-second order kinetic model. The adsorption process was determined to be controlled by three steps of diffusion mechanisms through the intra-particle model.The adsorption equilibrium was well described by the Langmuir,Freundlich,Redlich-Peterson,and Sips isotherm models. Batch and continuous flow experiments indicated that the LMWOAs exhibited inhibitory action,and as pH increased,the inhibitory action became weaker for all the three acids. The effect of LMWOAs concentration was not significant on inhibition. The effects of LMWOAs were closely related to reaction time.     

THz time-domain spectroscopy of amino acids

The optical characteristics of four kinds of amino acids （tyrosine, arginine, histidine and glutamine） filled with nitrogen at room temperature were studied by THz time-domain spectroscopy （THz-TDS）. Well-resolved absorption and refractive spectrums between 0.I and 2.8 THz were obtained based on the physical model for extracting the optical parameters of materials in THz range. The results not only fill up the spectra gap of amino acids in far-infrared range, supply data for amino acid molecular identification and conformation analysis, but also demonstrate significantly potential to promote the research and application of biological materials in bio-chemical and medical fields by THz-TDS.