Development of D-π-A organic dyes for discriminating HSA from BSA and study on dye-HSA interaction.

HSA (human serum albumin), a most abundant protein in blood serum, plays a key role in maintaining human health. Abnormal HSA level is correlated with many diseases, and thus has been used as an essential biomarker for therapeutic monitoring and biomedical diagnosis. Development of small-molecule fluorescent probes allowing the selective and sensitive recognition of HSA in in vitro and in vivo is of fundamental importance in basic biological research as well as medical diagnosis. Herein, we reported a series of new synthesized fluorescent dyes containing D-π-A constitution, which exhibited different optical properties in solution and solid state. Among them, dye M-H-SO3 with a hydrophilic sulfonate group at electron-acceptor part displayed selectivity for discrimination of HSA from BSA and other enzymes. Upon binding of dye M-H-SO3 with HSA, a significant fluorescence enhancement with a turn-on ratio about 96-fold was triggered. The detection limit was estimated to be âˆ¼ 40 nM. Studies on the interaction mechanism revealed that dye M-H-SO3 could bind to site III of HSA with a 1:1 binding stoichiometry. Furthermore, dye M-H-SO3 has been applied to determine HSA in real urine samples with good recoveries, which provided a useful method for HSA analysis in biological fluids.

Graphitic Armor: A Natural Molecular Sieve for Robust Hydrogen Electroxidation.

Carbon coating layers have been found to improve the catalytic performance of transition metals, which is usually explained as an outcome of electronic synergistic effect. Herein we reveal that the defective graphitic carbon, with a unique interlayer gap of 0.342 nm, can be a highly selective natural molecular sieve. It allows efficient diffusion of hydrogen molecules or radicals both along the in-plane and out-of-plane direction, but sterically hinders the diffusion of molecules with larger kinetic diameter (e.g., CO and O2) along the in-plane direction. As a result, poisonous species lager than 0.342 nm are sieved out, even when their adsorption on the metal is thermodynamically strong; at the same time, the interaction between H2 and the metal is not affected. This natural molecular sieve provides a very chance for constructing robust metal catalysts for hydrogen-relevant processes, which are more tolerant to chemical or electrochemical oxidation or CO-relevant poisoning.

Immunization with a Self-Assembled Nanoparticle Vaccine Elicits Potent Neutralizing Antibody Responses against EBV Infection.

Epstein-Barr virus (EBV) infection is a global health concern infecting over 90% of the population. However, there is no currently available vaccine. EBV primarily infects B cells, where the major glycoprotein 350 (gp350) is the main target of neutralizing antibodies. Given the advancement of nanoparticle vaccines, we describe rationally designed vaccine modalities presenting 60 copies of gp350 on self-assembled nanoparticles in a repetitive array. In a mouse model, gp350s on lumazine synthase (LS) and I3-01 adjuvanted with MF59 or aluminum hydroxide (Alhydrogel) elicited over 65- to 133-fold higher neutralizing antibody titers than the corresponding gp350 monomer to EBV. Furthermore, immunization with gp350D123-LS and gp350D123-I3-01 vaccine induced a Th2-biased response. For the nonhuman primate model, gp350D123-LS in MF59 elicited higher titers of total IgG and neutralizing antibodies than the monomeric gp350D123. Overall, these results support gp350D123-based nanoparticle vaccine design as a promising vaccine candidate for potent protection against EBV infection.

D-π-A type fluorescent dyes: Effect of π-bridge units on optical and G4 DNA binding properties.

Fluorescent solvatochromic dyes that are sensitive to the nature of local microenvironmental, have been explored as probes in applications ranging from the imaging biomolecules to understanding of basic biomolecule functions. To expand the scope of fluorescent solvatochromic dyes for G-quadruplex (G4) DNA structures, and to illustrate the relationship between structure and properties, three newly designed D-π-A type fluorescent dyes were synthesized by introducing diarylimidazole to carbazole skeleton linked to benzene, furan or thiophene π-conjugated bridge and connected with pyridinium acceptor, respectively. Their structural characteristics, optical properties, and G4 DNA binding properties were discussed in detail. In general, the incorporation of furan and thiophene as π-conjugated bridges leads the better conjugation and molecular coplanarity with more efficient intramolecular charge transfer (ICT) effect compared with benzene bridge. The fluorescence intensities induced upon interaction were found that TP-6 with thiophene π-conjugated bridge had the strongest response toward G4 DNAs. In addition, the application of this dye as a fluorescent agent for living cell imaging was also demonstrated.

[Qianlieping capsule plus alpha-blocker for chronic non-bacterial prostatitis: analysis of 220 cases].

OBJECTIVE: To investigate the clinical effects of Qianlieping Capsule combined with alpha-receptor blocker tamsulosin on chronic non-bacterial prostatitis (CNBP). METHODS: We assigned 220 CNBP patients to three groups to receive oral Qianlieping Capsule (2.0 g tid) plus alpha-receptor blocker tamsulosin (0.2 mg qd) (n = 98), Qianlieping Capsule alone at 2.0 g tid (n = 66), and tamsulosin alone at 0.2 mg qd (n = 56) , respectively. After 6 weeks of medication, we assessed the therapeutic effects according to the NIH-CPSI scores and the number of small particles of lecithin (SPL) in the prostatic fluid after treatment. RESULTS: Qianlieping Capsule alone increased the number of SPL by 46.9% and reduced the NIH-CPSI score by 24.4%. Combination of Qianlieping and tamsulosin more significantly increased the number of SPL (61.4%) and decreased the NIH-CPSI score (42.3%) than tamsulosin alone (33.7% and 28.6%) (P < 0.01). CONCLUSION: Qianlieping Capsule chronic is effective for chronic non-bacterial prostatitis, and the combination of Qianlieping Capsule with tamsulosin produces even better effect than tamsulosin alone.

Precise diagnosis of three top cancers using dbGaP data.

The challenge of decoding information about complex diseases hidden in huge number of single nucleotide polymorphism (SNP) genotypes is undertaken based on five dbGaP studies. Current genome-wide association studies have successfully identified many high-risk SNPs associated with diseases, but precise diagnostic models for complex diseases by these or more other SNP genotypes are still unavailable in the literature. We report that lung cancer, breast cancer and prostate cancer as the first three top cancers worldwide can be predicted precisely via 240-370 SNPs with accuracy up to 99% according to leave-one-out and 10-fold cross-validation. Our findings (1) confirm an early guess of Dr. Mitchell H. Gail that about 300 SNPs are needed to improve risk forecasts for breast cancer, (2) reveal an incredible fact that SNP genotypes may contain almost all information that one wants to know, and (3) show a hopeful possibility that complex diseases can be precisely diagnosed by means of SNP genotypes without using phenotypical features. In short words, information hidden in SNP genotypes can be extracted in efficient ways to make precise diagnoses for complex diseases.

[Correlation of the prognosis of chronic prostatitis/chronic pelvic pain syndrome with psychological and other factors: a Cox regression analysis].

OBJECTIVE: To establish the role of psychological factors in the etiology and symptomatology of chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS), analyze the influence of the psychological obstacles and other relative factors on the prognosis of CP/CPPS by univariate and multivariate Cox regression analyses, and provide a scientific basis for psychotherapy of the problem. METHODS: A total of 291 CP/CPPS patients and 100 normal controls were investigated in age, education, occupation, character, disease course, NIH chronic prostatitis syndrome index (NIH-CPSI) and leukocyte count in EPS and by self-rating anxiety scale (SAS) and self-rating depression scale (SDS) to establish the psychological factors related with CP/CPPS. Then, all the CP/CPPS patients were treated with the same method and followed up for 6 weeks. Based on the therapeutic results, the influence of psychological and other relative factors on the prognosis of CP/CPPS was analyzed with univariate and multivariate Cox regression. RESULTS: All together 258 valid questionnaires were collected from the patients and 87 from the normal controls. Of the 258 CP/CPPS patients, the mean scores on SAS and SDS were 42.8 +/- 11.43 and 48.15 +/- 11.49 respectively, both significantly higher than those of the controls (32.12 +/- 9.68 and 35.12 +/- 10.81) (P < 0.01). The rates of anxiety, depression and anxiety and/or depression in the CP/CPPS group were 25.97, 21.71 and 34.50 % respectively, all significantly higher than in the control group (P < 0.01). The rate of introversion was significantly higher while that of extroversion significantly lower in the former than in the latter (P < 0.01). The total effectiveness rate of treatment was 70.54 % in the CP/CPPS patients. Univariate and multivariate analyses with Cox regression revealed that anxiety, depression and disease course were the definite factors that negatively affected the prognosis of CP/CPPS, while the other factors, such as age, CPSI, character and leukocyte count in EPS had no influence. CONCLUSION: Such psychological obstacles as anxiety and depression play an important role in the pathogenesis, development and prognosis of CP/CPPS. In the treatment of CP/ CPPS, importance should be attached to the patients'psychological status and proper psychological intervention is sometimes necessary.

Predictors of clinical outcome after minimally invasive percutaneous nephrolithotomy for renal calculus.

To investigate all the predictors of operative duration, hospital stay and stone-free rate post-minimally invasive percutaneous nephrolithotomy (MPCNL) and to establish a logistic regression formula to predict the probability of stone-free post-MPCNL. From August 2009 to August 2012, 396 patients were enrolled in the present study. The patients' characteristics, history, laboratory examination and imaging information were used as independent variables, and operative duration, hospital stay, residuals (≥4 mm) as outcomes. Univariate and multiple regression analysis were performed to determine independent variables. According to the result of multiple logistic regression analysis, a logistic regression formula was established to predict the stone-free probability post-MPCNL. The predictors of operative duration were type of stones and stone burden. Factors affecting hospital stay included leucocytes, stone burden, type of stones and hemoglobin. Residuals were significantly related with stone burden and type of stones. With the above results, we developed a logistic regression formula, which can effectively predict the probability of stone-free with 91.7% of sensitivity, 70.4% of specificity and 85.9% of overall accuracy.

Anuria and abdominal pain induced by ceftriaxone-associated ureterolithiasis in adults.

Ceftriaxone is known to cause biliary pseudolithiasis and, rarely, nephrolithiasis mainly in children. However, we reported the development of bilateral distal ureteral ceftriaxone-associated lithiasis in 7 adults, which suggests that the risk of ureterolithiasis impaction should be considered when treating patients with ceftriaxone, even in adults. To avoid strengthening greater renal damage, ureteroscopic insertion of double J stents may be an alternative management for patients with ureteral ceftriaxone-associated lithiasis.

Target detection and recognition improvements by use of spatiotemporal fusion.

We developed spatiotemporal fusion techniques for improving target detection and automatic target recognition. We also investigated real IR (infrared) sensor clutter noise. The sensor noise was collected by an IR (256 x 256) sensor looking at various scenes (trees, grass, roads, buildings, etc.). More than 95% of the sensor pixels showed near-stationary sensor clutter noise that was uncorrelated between pixels as well as across time frames. However, in a few pixels (covering the grass near the road) the sensor noise showed nonstationary properties (with increasing or decreasing mean across time frames). The natural noise extracted from the IR sensor, as well as the computer-generated noise with Gaussian and Rayleigh distributions, was used to test and compare different spatiotemporal fusion strategies. Finally, we proposed two advanced detection schemes: the double-thresholding the reverse-thresholding techniques. These techniques may be applied to complicated clutter situations (e.g., very-high clutter or nonstationary clutter situations) where the traditional constant-false-alarm-ratio technique may fail.