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Refractory diabetic wounds are associated with high incidence, mortality, and recurrence rates and are a devastating and rapidly growing clinical problem. However, treating these wounds is difficult owing to uncontrolled inflammatory microenvironments and defective angiogenesis in the affected areas, with no established effective treatment to the best of our knowledge. Herein, we optimized a dual functional therapeutic agent based on the assembly of LL-37 peptides and diblock copolymer poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS). The incorporation of PEG-PPS enabled responsive or controlled LL-37 peptide release in the presence of reactive oxygen species (ROS). LL-37@PEG-PPS nanomicelles not only scavenged excessive ROS to improve the microenvironment for angiogenesis but also released LL-37 peptides and protected them from degradation, thereby robustly increasing angiogenesis. Diabetic wounds treated with LL-37@PEG-PPS exhibited accelerated and high-quality wound healing in vivo. This study shows that LL-37@PEG-PPS can restore beneficial angiogenesis in the wound microenvironment by continuously providing angiogenesis-promoting signals. Thus, it may be a promising drug for improving chronic refractory wound healing. [ABSTRACT FROM AUTHOR]

BACKGROUND: Quadratus lumborum block (QLB) has been found to be advantageous for laparoscopic colorectal surgery. This study hypothesized that preoperative anterior QLB at lateral supraarcuate ligament (QLB-LSAL) would decrease postoperative opioid usage and offer improved analgesia within the context of multimodal analgesia compared with lateral QLB (LQLB) for laparoscopic colorectal surgery. STUDY DESIGN: In this randomized controlled trial, 82 American Society of Anesthesiologists physical status I to III class colorectal cancer patients undergoing laparoscopic radical resection were enrolled and randomly assigned to receive either LQLB or QLB-LSAL (0.375% ropivacaine 0.3 mL/kg bilaterally for each group). The primary outcomes were the total intravenous morphine equivalent consumption at 24 hours postoperatively. RESULTS: Intravenous morphine equivalent consumption at 24 hours postoperatively was significantly reduced in the QLB-LSAL group compared with that in the LQLB group with per-protocol analysis (29.2 ± 5.8 vs 40.5 ± 9.6 mg, p < 0.001) and intention-to-treat analysis (29.6 ± 6.1 vs 40.8 ± 9.5 mg, p < 0.001). Time to first patient-controlled analgesia request was notably longer in the QLB-LSAL group than that in the LQLB group (10.4 ± 3.9 vs 3.7 ± 1.5 hours, p < 0.001). CONCLUSIONS: Preoperative bilateral ultrasound-guided QLB-LSAL reduces morphine usage and extends the duration until the first patient-controlled analgesia demand within the framework of multimodal analgesia when compared with LQLB after laparoscopic colorectal surgery. [ABSTRACT FROM AUTHOR]

The phenotypic and genetic links between body fat phenotypes and primary open-angle glaucoma (POAG) are unclear. We conducted a meta-analysis of relevant longitudinal epidemiological studies to evaluate the phenotypic link. To identify genetic links, we performed genetic correlation analysis and pleiotropy analysis of genome-wide association study summary statistics datasets of POAG, intraocular pressure (IOP), vertical cup-to-disc ratio, obesity, body mass index (BMI), and waist-to-hip ratio. In the meta-analysis, we first established that obese and underweight populations have a significantly higher risk of POAG using longitudinal data. We also discovered positive genetic correlations between POAG and BMI and obesity phenotypes. Finally, we identified over 20 genomic loci jointly associated with POAG/IOP and BMI. Among them, the genes loci CADM2, RP3-335N17.2, RP11-793K1.1, RPS17P5, and CASC20 showed the lowest false discovery rate. These findings support the connection between body fat phenotypes and POAG. The newly identified genomic loci and genes render further functional investigation. [ABSTRACT FROM AUTHOR]

Lithium (Li) is one of the most important light elements that was primordially synthesized in the Big Bang Nucleosynthesis (BBN). It is also an element that confused astrophysicists for decades, as its observed abundance often contradicts with the theoretical prediction in many different types of celestial objects. Li-rich giant stars are such objects. Their atmospheres contain anomaly high Li abundance than that expected by the standard stellar evolution model. Although the first Li-rich giant star was discovered almost 40 years ago, their origin is still being debated. With the launch of massive spectroscopic survey program such as the Large Sky Area Multi-Object Fiber Spectroscopy Telescope (LAMOST) survey, the extending of available asteroseismology data from space satellites (such as Kepler), and the developments of data-driven techniques, breakthroughs have been archived in the field of Li-rich studies. In this paper, we review the progress that was made during the past four decades, and present our up-to-date understanding to Li-rich giant stars. [ABSTRACT FROM AUTHOR]

The neutral lipids from the diatom Phaeodactylum tricornutum are a valuable substance with a vital role in biofuel. Increasing the neutral lipid content of P. tricornutum through nutritional stress, such as nitrogen stress or genetic engineering, is often accompanied by reduced growth, which limits the development of microalgae-derived biofuels. Manganese is an essential trace element for plant growth and plays a key role in the light reactions of photosynthesis. This study aimed to determine whether Mn2+ can increase the neutral lipid content. We investigated the effects of Mn2+ on growth, neutral lipid content, photosynthetic pigment content, and fatty acid and photosynthesis-related gene expression and enzyme abundance in P. tricornutum. The algae were exposed to different concentrations of Mn2+ and monitored for growth and neutral lipid and photosynthetic pigment contents. After 7 days of culture, neutral lipid levels were markedly increased in algae exposed to 500 μg·L-1 Mn2+ (1.44 times higher than the control group without Mn2+). To confirm the molecular mechanism of this effect in P. tricornutum treated with Mn2+, the expression of key genes in the fatty acid synthesis pathway (ACC1, LACS1, AGPAT, MCAT) and C4 pathway (ME1, PEPCK1, PEPC, PPDK, CA) were determined by real-time polymerase chain reaction. The expression of genes involved in these pathways reached their peak at a concentration of 500 μg·L-1 Mn2+, consistent with the change in neutral lipid content. Based on these results, we concluded that the neutral lipid content in P. tricornutum was enhanced by Mn2+, likely as a result of increased production of enzymes in the C4 pathway. [ABSTRACT FROM AUTHOR]

Background: The CAV1‐CAV2 locus has been associated with primary open‐angle glaucoma (POAG) and intraocular pressure. However, its association with normal‐tension glaucoma (NTG) was inconclusive. Therefore, we evaluated this association in Chinese and Japanese. Methods: Two single‐nucleotide polymorphisms (SNPs, rs4236601 and rs1052990) from previous genome‐wide association studies of POAG were genotyped in a total of 2220 study subjects: a Hong Kong Chinese cohort of 537 NTG patients and 490 controls, a Shantou Chinese cohort of 102 NTG and 731 controls and an Osaka Japanese cohort of 153 NTG and 207 controls. Subgroup analysis by gender was conducted. Outcomes from different cohorts were combined using meta‐analysis. Results: SNP rs4236601 was significantly associated with NTG in the two Chinese cohorts (Pmeta =.0019, OR = 4.55, I2 = 0). In contrast, rs4236601 was monomorphic in the Osaka cohort. The association of rs1052990 was insignificant in a meta‐analysis combining Chinese and Japanese cohorts (Pmeta =.81, OR = 1.05; I2 = 64%), and the OR tended towards opposite directions between Chinese (OR = 1.26) and Japanese (OR = 0.69). Gender‐specific effects of the SNPs were not statistically significant in the logistic regression or Breslow‐day tests of ORs (P >.05), although rs4236601 was significant in males (P =.0068; OR = 10.30) but not in females (P =.14; OR = 2.65) in the meta‐analysis of Chinese subjects. Conclusions: In this study, we confirmed the association of rs4236601 at the CAV1‐CAV2 locus with NTG in Chinese. SNP rs4236601 is monomorphic, and rs1052990 tends towards a different direction in the Japanese cohort. Further studies are warranted to verify the ethnic difference and gender‐specific effects of this locus. [ABSTRACT FROM AUTHOR]

Abstract The purpose of the study was to evaluate the association profiles of the SIX6 locus with primary open-angle glaucoma (POAG) in southern Chinese and Japanese. In this study, we tested single marker and haplotype-based associations of 11 tagging single nucleotide polymorphisms (SNPs) covering the SIX6 locus with POAG in a Hong Kong Chinese cohort (N = 1402). A novel SNP (i.e., rs12436579) and two SNPs (i.e., rs33912345 and rs10483727) from previous genome-wide association studies were further tested in a Chinese cohort from Shantou (N = 888) and a Japanese cohort from Osaka (N = 463). Results from the three cohorts were meta-analysed using a random-effect model. We found rs12436579, which has not been previously reported, was associated with POAG in Hong Kong and Shantou Chinese (P combined = 4.3 × 10−5, OR = 0.72, I2 = 0). Additionally, we replicated the association of one known SNP, rs33912345 (P combined = 0.0061, OR = 0.69, I2 = 45%), with POAG in the Chinese cohorts but not in the Japanese cohort (P > 0.6). Another known SNP, rs10483727, was nominally associated with POAG in the two Chinese cohorts (P combined = 0.017, OR = 0.70, I2 = 53%). All these three SNPs were significantly associated with POAG when the three cohorts were combined in meta-analysis (P combined <0.005). Furthermore, two haplotypes, C-C (P combined = 1.13 × 10−5, OR = 1.41, I2 = 0) and A-A (P combined = 0.045, OR = 0.68, I2 = 70%), defined by rs33912345-rs12436579 were associated with POAG in Chinese but not in Japanese. In conclusion, this study confirmed the association between two GWAS SNPs in SIX6 (rs33912345 and rs10483727) and POAG. Also, a SNP, rs12436579, not associated with POAG before, was found to be associated with POAG in Chinese. Further studies are warranted to elucidate the role of this novel SNP in POAG. Highlights • Validation of reported association between the SIX6 SNPs and POAG. • Identification of a novel SNP rs12436579 associated with POAG in Southern Chinese. • Haplotype rs33912345-rs12436579 had a stronger association than single SNP. • Different association patterns of SIX6 with POAG between Chinese and Japanese. [ABSTRACT FROM AUTHOR]

This review compared the clinical results of transepithelial corneal crosslinking (CXL) to epithelium-off (epi-off) CXL in progressive corneal ectasia using a metaanalysis. The Cochrane databases and Medline were searched for randomized controlled trials (RCTs). Seven RCTs involving 505 eyes that met the eligibility criteria were identified. The epi-off CXL group showed significantly better outcomes in postoperative changes in maximum keratometry (K) during 1-year observation periods. Transepithelial CXL resulted in significantly greater post-treatment central corneal thickness and best spectacle-corrected visual acuity (BSCVA). The presence of a postoperative demarcation line was significantly more frequent after epi-off CXL than that after transepithelial CXL. No statistically significant difference was found between other parameters. Although patients in the transepithelial CXL group demonstrated a greater improvement in BSCVA compared with patients in the epi-off CXL group at the 1 year follow-up, transepithelial CXL had less impact on halting progressive corneal ectasia in terms of maximum K than epi-off CXL. [ABSTRACT FROM AUTHOR]

This paper focuses on the improved design of Tc bearing's structure form. A sand transmission groove is designed around the outer ring of Tc bearing to make it easy to remove solid particles, and the dynamic pressure Reynolds equation of Tc bearing is solved and the static characteristics of two structures of Tc bearing are compared and analyzed. Overall, conclusions are drawn: the carrying capacity of Tc bearing with the sand transmission groove is less than that of the original Tc bearing; the end discharging capacity of Tc bearing with the sand transmission groove is more than that of the original Tc bearing, which is in favor of the removal of solid particles from the Tc bearing and the enhancement of sand removal function; improving the dynamic characteristics of the liquid film of Tc bearing, Tc bearing with the sand transmission groove is suitable for the rotor system with high-speed light-load of MWD. [ABSTRACT FROM AUTHOR]

Background: This study was aimed at investigating whether metformin can reverse the resistance of ovarian cancer cells to cisplatin and exploring the underlying mechanism.Methods: Ovarian cancer cell proliferation in vitro was evaluated using a CCK-8 assay. The resistance index of platinum-resistant ovarian cancer cells was determined and cell cycle and apoptosis rate determined by annexin V/propidium iodide double-staining in CP70 cells. Western blotting was used to determine IGF1, IGF1R, AKT, p-IGF1, p-IGF1R, p-AKT, and MRP2 levels in cells treated with different concentrations of metformin and LY29400, an inhibitor of the insulin-like growth factor pathway. Changes in gene expression levels of MRP2, IGF1, IGF1R, and AKT were determined by fluorescence real-time quantitative PCR assay of CP70 cells treated with metformin. Tumors of human ovarian cancer cell lines CP70 and A2780 were established by subcutaneous transplantation of cells in nude mice and the effect of metformin on MRP2 expression and tumor inhibition assessed.Results: The IC50 value of cisplatin in CP70 cells decreased significantly as metformin concentration increased (P < 0.05). The cell cycle distribution in CP70 cells changed with metformin treatment; the percentage of cells in the G0/G1 phase, as well as the natural apoptosis rate was significantly increased with metformin treatment (P < 0.05). IGF1, IGF1R, AKT p-IGF1, p-IGF1R, and p-Akt protein expression was enhanced dose-dependently with metformin, and was also significantly changed by treatment of CP70 cells with 0 mM metformin +10 mM LY294002. Moreover, changes in the expression of MRP2, IGF1, IGF1R, and AKT was metformin-concentration dependent, and was significantly different from that in the untreated control group (P < 0.05). In nude mice, the tumor volumes of the cisplatin-treated groups were significantly less than in the control group, and was further suppressed by co-treatment with cisplatin and metformin (P < 0.05), indicating that these 2 drugs had a synergistic effect on tumor inhibition.Conclusion: Metformin can improve the sensitivity of ovarian cancer CP70 cells to cisplatin in a concentration-dependent manner by activating the AKT signaling pathway, inhibiting the IGF1R signaling pathway, and reducing MRP2 expression. [ABSTRACT FROM AUTHOR]

According to the special working environment of drilling proposed design parameters of distance sleeve; The Ansoft Maxwell software is used to optimize the magnetic coupling, and the optimized design process is illustrated with an example; The torque is studied under different rotation angles; The effects of magnetic steel thickness, magnet thickness and magnetic pole number on torque are studied respectively; With the development of the rare earth permanent magnet material, it is imperative to apply the no leakage magnetic coupling to petroleum drilling. [ABSTRACT FROM AUTHOR]

In this paper, through analyzing Tc bearing by the theory of Hydrodynamic lubrication, the unsteady Reynolds equation of Tc bearing under the dynamic-state condition is initially established. The formula of Tc bearing's liquid-film dimensionless stiffness coefficient and damping coefficient is derived. Furthermore, two kinds of the distribution curves of Tc bearing's liquid-film dimensionless stiffness coefficient, damping coefficient against Tc bearing's eccentricity ratio and width-diameter ratio are displayed respectively, and the stability criterion of liquid film is worked out and the angular speed of instability of bearing shaft is calculated. Overall, conclusions are drawn: downhole system improves the entire system's stability by enhancing the stiffness of bearing shaft itself. The improvement of the stability of bearing shaft itself, which can be done by altering the structure of Tc bearing and adopting better spiral flutes and ellipse groove can strengthen the whole system's stability. The high width-diameter ratio of Tc bearing increases the liquid film's stiffness coefficient and damping coefficient of Tc bearing. The rotational rate of rotary table is lower than half of that of the supporting system of Tc bearing. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate the efficacy of collagen cross-linking (CXL) one year after treatment for keratoconus compared to no treatment by summarizing randomized controlled trials (RCTs) using a systematic review. Methods. Trials meeting the selection criteria were quality appraised, and the data were extracted by two independent authors. The outcome parameters included maximum keratometry (Kmax), corneal thickness at the thinnest point, best spectacle-corrected visual acuity (BSCVA), uncorrected visual acuity (UCVA), spherical equivalent (SE) refraction, and cylindrical refraction one year after CXL. We compared the changes in the above parameters with the control group. Results. We identified five RCTs involving 289 eyes that met the eligibility criteria for this systematic review. The changes in BSCVA from baseline to one year exhibited a significant difference between the two groups. There was no statistically significant difference between the two groups for changes in corneal thickness and cylindrical refraction. We did not conduct a meta-analysis in Kmax, UCVA, and SE refraction because their I2 values were greater than 50%. Conclusions. According to the systematic review, CXL may be effective in halting the progression of keratoconus for one year under certain conditions, although evidence is limited due to the significant heterogeneity and paucity of RCTs. [ABSTRACT FROM AUTHOR]

Glycosaminoglycans (GAGs) are linear polysaccharides comprised of disaccharide repeat units, a hexuronic acid, glucuronic acid or iduronic acid, linked to a hexosamine, N-acetylglucosamine (GlcNAc) or N-acetylgalactosamine. GAGs undergo further modification such as epimerization and sulfation. These polysaccharides are abundant in the extracellular matrix and connective tissues. GAGs function in stabilization of the fibrillar extracellular matrix, control of hydration, regulation of tissue, organism development by controlling cell cycle, cell behavior and differentiation. Niche adapted bacteria express enzymes called polysaccharide lyases (PL), which degrade GAGs for their nutrient content. PL have been classified into 24 sequence-related families. Comparison of 3D structures of the prototypic members of these families allowed identification of distant evolutionary relationships between lyases that were unrecognized at the sequence level, and identified occurrences of convergent evolution. We have characterized structurally and enzymatically heparinase III from Bacteroides thetaiotaomicron (BtHepIII; gene BT4657), which is classified within the PL12 family. BtHepIII is a 72.5 kDa protein. We present the X-ray structures of two crystal forms of BtHepIII at resolution 1.8 and 2.4 Å. BtHepIII contains two domains, the N-terminal a-helical domain forming a toroid and the C-terminal β-sheet domain. Comparison with recently determined structures of two other heparinases from the same PL12 family allowed us to identify structural flexibility in the arrangement of the domains indicating open-close movement. Based on comparison with other GAG lyases, we identified Tyr301 as the main catalytic residue and confirmed this by site-directed mutagenesis. We have characterized substrate preference of BtHepIII toward sulfate-poor heparan sulfate substrate. [ABSTRACT FROM AUTHOR]

Topic Systematic review and meta-analysis of the genetic associations of primary angle-closure disease (PACD). Clinical Relevance To confirm the genetic biomarkers for PACD, including primary angle-closure glaucoma (PACG) and related phenotypes. Methods We searched in the MEDLINE and EMBASE databases for genetic studies of PACG or other PACD published from the start dates of the databases to May 11, 2015. We estimated the summary odds ratios (ORs) and 95% confidence intervals (CIs) for each polymorphism in PACG, primary angle-closure suspect (PACS), and primary angle-closure (PAC) using fixed- or random-effect models. We also performed sensitivity analysis to test the robustness of the results. Results Our literature search yielded 6463 reports. Among them, we identified 24 studies that fulfilled the eligibility criteria for meta-analysis, involving 28 polymorphisms in 11 genes/loci. We affirmed the association of PACG and combined PACS/PAC/PACG with 10 polymorphisms in 8 genes/loci, including COL11A1 (rs3753841-G, OR, 1.22; P = 0.00046), HGF (rs17427817-C, OR, 2.02; P = 6.9E-07; rs5745718-A, OR, 2.11; P = 9.9E-07), HSP70 (rs1043618, GG+GC, OR, 0.52; P = 0.0010), MFRP (rs2510143-C, OR, 0.66; P = 0.012; rs3814762-G, OR, 1.40; P = 0.0090), MMP9 (rs3918249-C, OR, 1.35; P = 0.034), NOS3 (rs7830-A, OR, 0.80; P = 0.036), PLEKHA7 (rs11024102-G, OR, 1.24; P = 8.3E-05), and PCMTD1-ST18 (rs1015213-A, OR, 1.59; P = 0.00013). Sensitivity analysis indicated that the results were robust. Conclusions In this study, we confirmed multiple polymorphisms in 8 genes/loci as genetic biomarkers for PACD, among which 3 were identified in a genome-wide association study ( COL11A1 , PLEKHA7, and PCMTD1-ST18 ), and 5 were identified in candidate gene studies ( HGF , HSP70 , MFRP , MMP9 , and NOS3 ). [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effect of picfeltarraenin IA (IA) on respiratory inflammation by analyzing its effect on interleukin (IL)-8 and prostaglandin E2 (PGE2) production. The expression of cyclooxygenase 2 (COX2) in human pulmonary adenocarcinoma epithelial A549 cells in culture was also examined. Human pulmonary epithelial A549 cells and the human monocytic leukemia THP-1 cell line were used in the current study. Cell viability was measured using a methylthiazol tetrazolium assay. The production of IL-8 and PGE2 was investigated using an enzyme-linked immunosorbent assay. The expression of COX2 and nuclear factor-κB (NF-κB)-p65 was examined using western blot analysis. Treatment with lipopolysaccharide (LPS; 10 μg/ml) resulted in the increased production of IL-8 and PGE2, and the increased expression of COX2 in the A549 cells. Furthermore, IA (0.1-10 µmol/l) significantly inhibited PGE2 production and COX2 expression in cells with LPS-induced IL-8, in a concentration-dependent manner. The results suggested that IA downregulates LPS-induced COX2 expression, and inhibits IL-8 and PGE2 production in pulmonary epithelial cells. Additionally, IA was observed to suppress the expression of COX2 in THP-1 cells, and also to regulate the expression of COX2 via the NF-κB pathway in the A549 cells, but not in the THP-1 cells. These results indicate that IA regulates LPS-induced cytokine release in A549 cells via the NF-κB pathway. [ABSTRACT FROM AUTHOR]

Sushi domain containing 2 (SUSD2) has been identified as a gene encoding an 822-amino acid protein, which contains a transmembrane domain and functional domains inherent to adhesion molecules. Previous studies have reported that increased expression of SUSD2 has a critical role in tumorigenesis in human breast cancer. However, to the best of our knowledge, SUSD2 expression status and its correlation with the clinicopathological features of non-small cell lung cancer (NSCLC) have not previously been investigated. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were used to evaluate SUSD2 messenger RNA (mRNA) and protein expression in NSCLC and adjacent normal lung tissues. The clinicopathological significance of SUSD2 was investigated by immunohistochemical analysis of an NSCLC tissue microarray. Receiver operating characteristic analysis was used to determine the cut-off score for positive expression of SUSD2. Furthermore, the correlation between SUSD2 expression and the clinicopathological features of NSCLC was analyzed by χ² test. The results revealed that SUSD2 mRNA (P<0.0001) and protein (P<0.0001) expression levels were significantly decreased in NSCLC tissues compared with those of adjacent normal tissues. When the SUSD2 positive expression percentage was determined to be >47.5% (area under ROC curve, 0.799; P<0.000), positive expression of SUSD2 was observed in 100% (32/32) of normal lung tissues and 55% (88/160) of NSCLC tissues by immunohistochemistry (χ²=21.160; P<0.000). Furthermore, it was demonstrated that the reduced SUSD2 protein levels in cancer tissues were positively correlated with poor histological grade (χ²=41.764; P<0.000), advanced clinical stage (χ²=10.790; P=0.013), higher pT (χ²=9.070; P=0.028) and positive regional lymph node metastasis (χ²=15.399; P=0.002). In conclusion, these data suggest that the reduced expression of SUSD2 is associated with the progression of NSCLC and may have a role in the pathogenesis of NSCLC. [ABSTRACT FROM AUTHOR]

Sineoculis homeobox homolog 1 (Six1), normally a developmentally restricted transcriptional regulator, is frequently dysregulated in mutiple cancers. Increasing evidences show that overexpression of Six1 plays a key role in tumorigenesis. However, the Six1 expression status and its relationship with the clinicopathological characteristics in prostate cancer were unclear. In this study, the mRNA and protein levels of Six1 in prostate cancer tissues and normal prostate tissues were evaluated. The clinicopathological significance of Six1 was investigated by immunohistochemistry (IHC) on a prostate cancer tissue microarray. The cut-off score for high expression of Six1 was determined by the receiver-operating characteristic (ROC) analysis. The correlation between Six1 protein expression and clinicopathological characteristics of prostate cancer was analyzed by Chi-square test. Increased expression of Six1 protein was observed in the majority of prostate cancer, compared with their paired adjacent normal prostate tissues. When Six1 high expression percentage was determined to be above 55 % (area under ROC curve = 0.881, P = 0.000), high expression of Six1 was observed in 55.6 % (80/144) of prostate cancer tissues and low expression of Six1 was observed in all normal prostate tissues by IHC. Increased expression of Six1 in patients was correlated with high histological grade (χ2 = 58.651, P = 0.00), advanced clinical stage (χ2 = 57.330, P = 0.000), high Gleason score (χ2 = 63.480, P = 0.000), high primary tumor grade (χ2 = 57.330, P = 0.000) and positive regional lymph node metastasis (χ2 = 19.294, P = 0.000). Furthermore, univariate and multivariate survival analysis suggested that Six1 was an independent prognostic indicator for overall survival (P < 0.05). This study suggests that Six1 could be served as an additional biomarker in identifying prostate cancer patients at risk of tumor progression, might potentially be used for predicting survival outcome of patients with prostate cancer. [ABSTRACT FROM AUTHOR]

Radiofrequency ablation (RFA) causes coagulative necrosis of tumor tissue and the production of local tumor protein debris. These fragments of tumor protein debris contain a large number of various antigens, which can stimulate a specific cellular immune response. In the present study, dendritic cells (DCs) were loaded with tumor protein lysate antigens that were produced in situ by RFA, and were used to treat murine colon carcinoma in combination with cytokine-induced killer (CIK) cells. Subsequent to the treatment of murine colon carcinoma by RFA, the in situ supernatant of tumor lysis was collected and the DCs were loaded with the lysate antigen to generate Ag-DCs. CIK cells induced from the spleen cells of mice were co-cultured with Ag-DCs to generate Ag-DC-CIK cells. The results revealed that the Ag-DC-CIK cells exhibited strong antitumor activity in vitro and in vivo. The morphology and immunophenotypes of these cells were determined using microscopy and flow cytometry, respectively. The cytotoxic activity of Ag-DC-CIK cells was determined using a CCK-8 assay. To establish a mouse model, mice were randomized into Ag-DC-CIK, DC-CIK, CIK and PBS control groups and monitored for tumor growth and survival time. ANOVA was used to compare the trends in the three groups for implanted tumor volumes. The log-rank test was used to compare the survival time. The present findings indicated that DCs loaded with the protein lysate antigens of tumors, produced in situ by RFA, combined with CIK cells may be a novel strategy for cancer treatment. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a major cause of severe vision loss in elderly people. Diabetes mellitus is a common endocrine disorder with serious consequences, and diabetic retinopathy (DR) is the main ophthalmic complication. DR and AMD are different diseases and we seek to explore the relationship between diabetes and AMD. MEDLINE, EMBASE, and the Cochrane Library were searched for potentially eligible studies. Studies based on longitudinal cohort, cross-sectional, and case-control associations, reporting evaluation data of diabetes as an independent factor for AMD were included. Reports of relative risks (RRs), hazard ratios (HRs), odds ratio (ORs), or evaluation data of diabetes as an independent factor for AMD were included. Review Manager and STATA were used for the meta-analysis. Twenty four articles involving 27 study populations were included for meta-analysis. In 7 cohort studies, diabetes was shown to be a risk factor for AMD (OR, 1.05; 95% CI, 1.00–1.14). Results of 9 cross-sectional studies revealed consistent association of diabetes with AMD (OR, 1.21; 95% CI, 1.00–1.45), especially for late AMD (OR, 1.48; 95% CI, 1.44–1.51). Similar association was also detected for AMD (OR, 1.29; 95% CI, 1.13–1.49) and late AMD (OR, 1.16; 95% CI, 1.11–1.21) in 11 case-control studies. The pooled ORs for risk of neovascular AMD (nAMD) were 1.10 (95% CI, 0.96–1.26), 1.48 (95% CI, 1.44–1.51), and 1.15 (95% CI, 1.11–1.21) from cohort, cross-sectional and case-control studies, respectively. No obvious divergence existed among different ethnic groups. Therefore, we find diabetes a risk factor for AMD, stronger for late AMD than earlier stages. However, most of the included studies only adjusted for age and sex; we thus cannot rule out confounding as a potential explanation for the association. More well-designed prospective cohort studies are still warranted to further examine the association. [ABSTRACT FROM AUTHOR]

Background Pin2/TRF1 binding protein X1 (PinX1) has been identified as an endogenous telomerase inhibitor and a major haploinsufficient tumor suppressor gene. Increasing evidence suggests that reduced expression of PinX1 plays a key role in tumorigenesis. However, the PinX1 expression status and its correlation with the clinicopathological features in prostate cancer (PCa) have not been investigated. Methods PinX1 mRNA and protein expression in PCa and adjacent normal prostate tissues were evaluated by real-time quantitative RT-PCR (qRT-PCR) and western blotting. The clinicopathological significance of PinX1 was investigated by immunohistochemistry (IHC) analysis on a PCa tissue microarray (TMA). The cut-off score for positive expression of PinX1 was determined by the receiver operating characteristic (ROC) analysis. The correlation between PinX1 expression and clinicopathological features of PCa was analyzed by Chi-square test. Results Reduced expression of PinX1 mRNA and protein was observed in the majority of PCa, compared with their paired adjacent normal prostate tissues. When PinX1 positive expression percentage was determined to be above 60% (area under ROC curve = 0.833, P = 0.000), positive expression of PinX1 was observed in 100% (8/8) of normal prostate tissues and 32.5% (13/40) of PCa tissues by IHC. Reduced expression of PinX1 in patients was correlated with advanced clinical stage (χ2 = 10.230, p = 0.017), high Gleason score (χ2 = 4.019, p = 0.045), positive regional lymph node metastasis (χ2 = 10.852, p = 0.004) and distant metastasis (χ2 = 7.965, p = 0.005). Conclusions Our findings suggest that reduced expression of PinX1 is correlates to progressive features in patients with PCa and may serve as a potential marker for diagnosis. [ABSTRACT FROM AUTHOR]

Bladder cancer is a commom malignancy in the urinary tract that is influenced by genetic and environmental factors. The role of functional polymorphisms in the methy-lenetetrahydrofolate reductase (MTHFR) gene with bladder cancer risk remains to be determined. This meta-analysis was performed to derive a more precise estimation of MTHFR Ala222Val and Glu429Ala polymorphisms and bladder cancer risk. Data were collected with the last report up to September 2013. A total of 3,463 cases and 3,927 controls for Ala222Val, and 3,177 cases and 3,502 controls for Glu429Ala were analyzed. The pooled odds ratios (ORs) and 95% confidence interval (CI) were estimated for the association with bladder cancer risk. Overall, no significant associations of Ala222Val and Glu429Ala polymorphisms with bladder cancer risk were found (for Ala222Val: Val/Val vs. Ala/Ala: OR, 1.02; 95% CI: 0.80-1.29; Val/Ala vs. Ala/Ala: OR, 1.02; 95% CI: 0.92-1.12; dominant model: OR, 1.01; 95% CI: 0.87-1.17; recessive model: OR, 1.00; 95% CI: 0.87-1.15; and for Glu429Ala: Ala/Ala vs. Glu/Glu: OR, 1.11; 95% CI: 0.78-1.58; Ala/Glu vs. Glu/Glu: OR, 1.16; 95% CI: 0.95-1.40; dominant model: OR, 1.15; 95% CI: 0.94-1.41; recessive model: OR, 0.96; 95% CI: 0.79-1.15). In stratified analyses by ethnicity, significant associations were observed for Glu429Ala polymorphism in individuals of Middle Eastern descent (Ala/Glu vs. Glu/Glu: OR, 2.11; 95% CI: 1.26-3.53; dominant model: OR, 2.16; 95% CI: 1.16-4.01; recessive model: OR, 1.82; 95% CI: 1.11-3.01). This meta-analysis demonstrated that overall there was no association of MTHFR Ala222Val and Glu429Ala polymorphisms with bladder cancer risk. However, in the stratified analysis by ethnicity the MTHFR Glu429Ala polymorphism was significantly associated with increased bladder cancer risk in individuals of Middle Eastern descent. [ABSTRACT FROM AUTHOR]

As a major tumor suppressor gene, the role of PinX1 in breast cancer and its molecular mechanism remain unclear. In this study, overexpression of PinX1 was generated in 3 breast cancer cell lines, and knockdown of PinX1 was performed in a nontumorigenic breast cell line. The regulation of PinX1 on cell proliferation and cell cycle was observed. A microarray-based lncRNA and mRNA expression profile screening was also performed. We found a lower growth rate, G0/G1 phase arrest, and S phase inhibition in the PinX1 overexpressed breast cancer cells, while a higher growth rate, decreased G0/G1 phase, and increased S phase rate in the PinX1 knocked-down nontumorigenic breast cell. A total of 977mRNAs and 631 lncRNAs were identified as differentially expressed transcripts between PinX1 overexpressed and control MCF-7 cells. Further analysis identified the involvement of these mRNAs in 52 cancer related pathways and various other biological processes. 11 enhancer-like lncRNAs and 25 lincRNAs with their adjacent mRNA pairs were identified as coregulated transcripts. Our results confirmed the role of PinX1 as a major tumor suppressor gene in breast cancer cell lines and provided information for further research on the molecular mechanisms of PinX1 in tumorigenesis. [ABSTRACT FROM AUTHOR]

Background Increasing evidence suggest that ubiquitin-proteasome system (UPS) plays a key role in tumorigenesis. HERC4 is a recently identified ubiqutin ligase. However, the expression status and biological functions of HERC4 in cancers are not clearly. Methods We evaluated the HERC4 expression in breast cancer cell lines and breast tumor tissues by quantitative real-time PCR and western blot analysis. To investigate the clinicopathological significance of HERC4, immunohistochemistry analysis for HERC4 was performed on a tissue microarray including 13 benign fibroadenoma, 15 intraductal carcinoma, 120 histologically confirmed invasive ductal carcinoma. Receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off score for positive expression of HERC4, when HERC4 positive expression percentage was above 60%, tumor was defined as "positive". Results HERC4 was up-regulated in breast cancer cell lines and breast tumor tissues compared to non-tumorigenic cell line and adjacent normal breast tissues. According to ROC analysis, HERC4 positive expression was detected in 1/16 (6.3%) of normal breast tissue, in 3/13 (23.1%) of fibroadenoma, in 6/15(40%) of intraductal carcinoma and 66/120 (55%) of invasive ductal carcinoma. Positive expression of HERC4 was positively correlated with pT status, pN status, clinical stage and histological grade of patients with invasive ductal carcinoma (p < 0.05). Conclusions Our findings suggest that HERC4 was a significant diagnostic marker for invasive ductal carcinoma of the breast. [ABSTRACT FROM AUTHOR]

Background: With the acceleration of industrialization in low or middle-income nations, the prevalence of respiratory symptoms among older adults is even more significant now in China. Contemporary treatments using Western medicine, such as anti-inflammatory regimens, may be effective in relieving the symptoms, but may have unexpected side effects. Some natural products may be effective in improving respiratory functions, yet their efficacies remain to be examined in randomized, placebo-controlled studies. To evaluate the effects of Lung Support Formula, a nutritional supplement which contains naturally derived Chinese herbal medicines, we conducted a clinical study among older adults in Shanghai, China. Methods: A total of 100 patients over 50 years old were recruited and blindly randomized into the treatment or control group. The subjects took either 1 Lung Support Formula capsule or a placebo capsule twice a day for 12 weeks. All subjects were followed-up every 4 weeks to perform investigative and clinical examinations. Repeated measure of analysis of variance was employed to compare the trend of respiratory symptoms scores between the 2 groups during 12 weeks of follow-up. Results: Fifty patients from the treatment group and 49 patients in the control group completed the 3-month follow-up. No adverse events were reported in the treatment duration. The percentage of patients reported to have chronic cough, chronic expectoration and chronic bronchitis were significantly decreased in the treatment group when compared with baseline after a 3-month intervention (P < 0.05). The respiratory symptoms scores declined gradually with the lapse of time (P < 0.05) in the treatment group and there were no significant changes in the control group by repeated measure of analysis of variance (P > 0.05). Conclusions: The clinical research shows that use of Lung Support Formula shows significant improvements of respiratory symptoms and is well-tolerated in short-term use among older adults. An additional study involving more subjects and longer-term follow-up would be needed to provide convincing evidence of the improvement of respiratory symptoms in the treatment group. [ABSTRACT FROM AUTHOR]

In Chinese medicine, Xiexin decoction (XXD) has been used for the clinical treatment of diabetes for at least 1700 years. The present study was conducted to investigate the effective ingredients of XXD and their molecular mechanisms of antidiabetic nephropathy in rats. Rats with diabetes induced by high-fat diet and streptozotocin were treated with XXD extract for 12 weeks. XXD significantly improved the glucolipid metabolism disorder, attenuated albuminuria and renal pathological changes, reduced renal advanced glycation end-products, inhibited receptor for advanced glycation end-product and inflammation factors expression, suppressed renal nuclear factor-kB pathway activity, and downregulated renal transforming growth factor-βl. The concentrations of multiple components in plasma from XXD were determined by liquid chromatography and tandem mass spectrometry. Pharmacokinetic/pharmacodynamic analysis using partial least square regression revealed that 8 ingredients of XXD were responsible for renal protective effects via actions on multiple molecular targets. Our study suggests that the renal protective role of XXD with multiple effective ingredients involves inhibition of inflammation through downregulation of the nuclear factor-f?B pathway, reducing renal advanced glycation end-products and receptor for advanced glycation end-product in diabetic rats. [ABSTRACT FROM AUTHOR]

Significant amounts of pyrethroid pesticides are used throughout China. Previous studies have suggested that exposure to pesticides may increase the risk of childhood cancer; however, few studies have focused on pyrethroid metabolites. We investigated five nonspecific metabolites of pyrethroid pesticides found in children's urine and examined the correlation with childhood leukemia. We conducted a hospital-based case-control study of childhood acute lymphocytic leukemia (ALL) in Shanghai between 2010 and 2011. The study included 176 children aged 0-14 years and 180 controls matched for age and sex. Compared with those in the lowest quartiles of total and individual metabolites, the highest quartiles were associated with an approximate 2-fold increased risk of ALL [total metabolites: odds ratio (OR) = 2.75, 95% confidence interval (CI), 1.43-5.29; cis-DCCA: OR = 2.21, 95% CI, 1.16-4.19; trans-DCCA: OR = 2.33, 95% CI, 1.23-4.41; and 3-PBA: OR = 1.84, 95% CI, 1.00-3.38], and most of the positive trends were significant (p < 0.05). Our findings suggest that urinary levels of pyrethroid metabolites may be associated with an elevated risk of childhood ALL and represent a previously unreported quantitative exposure assessment for childhood leukemia. [ABSTRACT FROM AUTHOR]

Although glycopeptide antibiotics (GPAs), including vancomycin and teicoplanin, represent the most important class of anti-infective agents in the treatment of serious Gram-positive bacterial infections, their usefulness is threatened by the emergence of resistant strains. GPAs are complex natural products consisting of a heptapeptide skeleton assembled via nonribosomal peptide synthesis and constrained through multiple crosslinks, with diversity resulting from enzymatic modifications by a variety of tailoring enzymes, which can be used to produce GPA analogues that could overcome antibiotic resistance. GPA-modifying sulfo-transferases are promising tools for generating the unique derivatives. Despite significant sequence and structural similarities, these sulfotransferases modify distinct side chains on the GPA scaffold. To provide insight into the spatial diversity of modifications, we have determined the crystal structure of the ternary complex of bacterial sulfotransferase StaL with the cofactor product 3'-phosphoadenosine 5'-phosphate and desulfo-A47934 aglycone substrate. Desulfo-A47934 binds with the hydroxyl group on the 4-hydroxyphenylglycine in residue 1 directed toward the 3'-phosphoadenosine 5'-phosphate and hydrogen-bonded to the catalytic His67. Homodimeric StaL can accommodate GPA substrate in only one of the two active sites because of potential steric clashes. Importantly, the aglycone substrate demonstrates a flattened conformation, in contrast to the cup-shaped structures observed previously. Analysis of the conformations of this scaffold showed that despite the apparent rigidity due to crosslinking between the side chains, the aglycone scaffold displays substantial flexibility, important for enzymatic modifications by the GPA-tai-loring enzymes. We also discuss the potential of using the current structural information in generating unique GPA derivatives. [ABSTRACT FROM AUTHOR]

f one of its original memb~ [ABSTRACT FROM AUTHOR]

Background: Deletion in liver cancer gene (DLC1) and phosphorylated focal adhesion kinase (p-FAK) have recently been reported as metastasis-related genes. However, the roles and prognostic values of their expression in epithelial ovarian carcinomas (EOCs) remain unclear. Methods: The expression and prognostic value of DLC1 and p-FAK Y397 in EOC were evaluated by immunohistochemistry and multivariate analysis. Results: Low expression of DLC1 and high expression of p-FAK Y397 were found in the 76 cases of EOC. The expression of DLC1 and p-FAK Y397 were negatively correlated. Multivariate analysis showed that the combination of them was an independent prognostic marker of EOC (P = 0.0319). Conclusions: DLC1 and pFAK Y397 had an association with the clinicopathologic characteristics of EOC. Expression of neither of these genes was a prognostic factor alone, but the combination revealed a significant prognostic value in the 60 cases of advanced stage EOC. [ABSTRACT FROM AUTHOR]

Telomere maintenance is essential for protecting chromosome ends. Aberrations in telomere length have been implicated in cancer and aging. Telomere elongation by human telomerase is inhibited in cis by the telomeric protein TRF1 and its associated proteins. However, the link between TRF1 and inhibition of telomerase elongation of telomeres remains elusive because TRF1 has no direct effect on telomerase activity. We have previously identified one Pin2/TRF1-interacting protein, PinXl, that has the unique property of directly binding and inhibiting telomerase catalytic activity (Zhou, X. Z., and Lu, K. P. (2001) Cell 107, 347-359). However, nothing is known about the role of the PinX1-TRF1 interaction in the regulation of telomere maintenance. By identifying functional domains and key amino acid residues in PinXl and TRF1 responsible for the PinX1-TRF1 interaction, we show that the TRF homology domain of TRF1 interacts with a minimal 20amino acid sequence of PinXl via hydrophilic and hydrophobic interactions. Significantly, either disrupting this interaction by mutating the critical Leu-291 residue in PinXl or knocking down endogenous TRF1 by RNAi abolishes the ability of PinXl to localize to telomeres and to inhibit telomere elongation in cells even though neither has any effect on telomerase activityperse. Thus, the telomerase inhibitor PinXl is recruited to telomeres by TRF1 and provides a critical link between TRF1 and telomerase inhibition to prevent telomere elongation and help maintain telomere homeostasis. [ABSTRACT FROM AUTHOR]

The Escherichia coil dihydroxyacetone (Dha) kinase is an unusual kinase because (i) it uses the phosphoenolpyruvate carbohydrate: phosphotransferase system (PTS) as the source of high-energy phosphate, (ii) the active site is formed by two subunits, and (iii) the substrate is covalently bound to His218K* of the DhaK subunit. The PTS transfers phosphate to DhaM, which in turn phosphorylates the permanently bound ADP coenzyme of DhaL. This phosphoryl group is subsequently transferred to the Dha substrate bound to DhaK. Here we report the crystal structure of the E. coil Dha kinase complex, DhaK-DhaL. The structure of the complex reveals that DhaK undergoes significant conformational changes to accommodate binding of DhaL. Combined mutagenesis and enzymatic activity studies of kinase mutants allow us to propose a catalytic mechanism for covalent Dha binding, phosphorylation, and release of the Dha-phosphate product. Our results show that His56K is involved in formation of the covalent hemiaminal bond with Dha. The structure of H56NK with noncovalently bound substrate reveals a somewhat different positioning of Dha in the binding pocket as compared to covalently bound Dha, showing that the covalent attachment to His218K orients the substrate optimally for phosphoryl transfer. Asp109K is critical for activity, likely acting as a general base activating the γ-OH of Dha. Our results provide a comprehensive picture of the roles of the highly conserved active site residues of dihydroxyacetone kinases. [ABSTRACT FROM AUTHOR]

Although pediatric doses for biotherapeutics are often based on patients' body weight (mg/kg) or body surface area (mg/m2), linear body size dose adjustment is highly empirical. Growth and maturity are also important factors that affect the absorption, distribution, metabolism and excretion (ADME) of biologics in pediatrics. The complexity of the factors involved in pediatric pharmacokinetics lends to the reconsideration of body size based dose adjustment. A proper dosing adjustment for pediatrics should also provide less intersubject variability in the pharmacokinetics and/or pharmacodynamics of the product compared with no dose adjustment. Biological proteins and peptides generally share the same pharmacokinetic principle with small molecules, but the underlying mechanism can be very different. Here, pediatric and adult pharmacokinetic parameters are compared and summarized for selected biotherapeutics. The effect of body size on the pediatric pharmacokinetics for these biological products is discussed in the current review. [ABSTRACT FROM AUTHOR]

The crystal Structure of the urease maturation protein UreE from Helicobacter pylori has been determined in its apo form at 2.1 Å resolution, bound to Cu2+ at 2.7 Å resolution, and bound to Ni2+ at 3.1 Å resolution. Apo UreE forms dimers. while the metal-bound enzymes are arranged as tetramers that consist of a dimer of dimers associated around the metal ion through coordination by His 102 residues from each subunit of the tetramer. Comparison of independent subunits from different crystal forms indicates changes in the relative arrangement of the N- and C-terminal domains in response to metal binding. The improved ability of engineered versions of UreE containing hexahistidine sequences at either the N-terminal or C-terminal end to provide Ni2+ for the final metal sink (urease) is eliminated in the H102A version. Therefore, the ability of the improved Ni2+-binding versions to deliver more nickel is likely an effect of an increased local concentration of metal ions that can rapidly replenish transferred ions bound to His102. [ABSTRACT FROM AUTHOR]

The cysteine desulfurase IscS is a highly conserved master enzyme initiating sulfur transfer via persulfide to a range of acceptor proteins involved in Fe-S cluster assembly, tRNA modifications, and sulfur-containing cofactor biosynthesis. Several IscS-interacting partners including IscU, a scaffold for Fe-S cluster assembly; TusA, the first member of a sulfur relay leading to sulfur incorporation into the wobble uridine of several tRNAs; ThiI, involved in tRNA modification and thiamine biosynthesis; and rhodanese RhdA are sulfur acceptors. Other proteins, such as CyaY/frataxin and IscX, also bind to IscS, but their functional roles are not directly related to sulfur transfer. We have determined the crystal structures of IscS-IscU and IscS-TusA complexes providing the first insight into their different modes of binding and the mechanism of sulfur transfer. Exhaustive mutational analysis of the IscS surface allowed us to map the binding sites of various partner proteins and to determine the functional and biochemical role of selected IscS and TusA residues. IscS interacts with its partners through an extensive surface area centered on the active site Cys328. The structures indicate that the acceptor proteins approach Cys328 from different directions and suggest that the conformational plasticity of a long loop containing this cysteine is essential for the ability of IscS to transfer sulfur to multiple acceptor proteins. The sulfur acceptors can only bind to IscS one at a time, while frataxin and IscX can form a ternary complex with IscU and IscS. Our data support the role of frataxin as an iron donor for IscU to form the Fe-S clusters. [ABSTRACT FROM AUTHOR]

The cysteine desulfurase IscS is a highly conserved master enzyme initiating sulfur transfer via persulfide to a range of acceptor proteins involved in Fe-S cluster assembly, tRNA modifications, and sulfur-containing cofactor biosynthesis. Several IscS-interacting partners including IscU, a scaffold for Fe-S cluster assembly; TusA, the first member of a sulfur relay leading to sulfur incorporation into the wobble uridine of several tRNAs; ThiI, involved in tRNA modification and thiamine biosynthesis; and rhodanese RhdA are sulfur acceptors. Other proteins, such as CyaY/frataxin and IscX, also bind to IscS, but their functional roles are not directly related to sulfur transfer. We have determined the crystal structures of IscS-IscU and IscS-TusA complexes providing the first insight into their different modes of binding and the mechanism of sulfur transfer. Exhaustive mutational analysis of the IscS surface allowed us to map the binding sites of various partner proteins and to determine the functional and biochemical role of selected IscS and TusA residues. IscS interacts with its partners through an extensive surface area centered on the active site Cys328. The structures indicate that the acceptor proteins approach Cys328 from different directions and suggest that the conformational plasticity of a long loop containing this cysteine is essential for the ability of IscS to transfer sulfur to multiple acceptor proteins. The sulfur acceptors can only bind to IscS one at a time, while frataxin and IscX can form a ternary complex with IscU and IscS. Our data support the role of frataxin as an iron donor for IscU to form the Fe-S clusters. [ABSTRACT FROM AUTHOR]

Background: China is currently facing a rapid and widespread increase in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). The activities of female sex workers (FSWs) have contributed to the mounting epidemic of HIV/AIDS and other sexually transmitted diseases (STDs). Therefore, this study aimed to assess the HIV/AIDS-related knowledge, attitude and risk behaviors among FSWs operating in Shanghai China.Methods: A cross-sectional study was conducted in five districts of Shanghai, including three suburbs and two downtown locales. We adopted a cluster randomized sampling method to obtain ten geographic sites which consisted of one or more communities/villages proximal to a location where FSWs were accessible. A total of 324 FSWs from 109 Xitou Fang, massage parlors and hair salons who explicitly provided sexual services were enrolled in the study. Each participant completed a questionnaire survey and interview aimed to collect information on the individual's knowledge, attitude, and behaviors associated with risk for HIV/AIDs.Results: The overall correct answer rate of HIV/AIDS-related knowledge was 60.8%, and the knowledge of FSWs from downtown areas was significantly higher than those from suburban areas (P < 0.05). The percentage of FSWs who reported having experiences in commercial sexual services without the use of condoms was 33.6%. Condom slippage or breakage was reported as having occurred at least once by 51.2% of the FSWs. FSWs from suburban areas were found to more often engage in high-risk behaviors, including oral and anal sex, than those from downtown areas (P < 0.001). Many of the FSWs (65.7%) reported having non-client sexual partners (most were identified as boyfriends or husbands); however, condom usage with these partners were lower (34.3%).Conclusions: Based on the findings from our survey, we advise that promotion of HIV/AIDS-related knowledge be targeted towards FSWs in Shanghai, especially those operating in the suburbs. HIV prevention efforts, such as urging constant condom usage with both clients and steady partners, should be sustained and reinforced among the female sex workers population. [ABSTRACT FROM AUTHOR]

Three catabolic enzymes, UlaD, UlaE, and UlaF, are involved in a pathway leading to fermentation of ʟ-ascorbate under anaerobic conditions. UlaD catalyzes a β-keto acid decarboxylation reaction to produce ʟ-xylulose-5-phosphate, which undergoes successive epimerization reactions with UlaE (ʟ-xylulose-5-phosphate 3-epimerase) and UlaF (ʟ-ribulose-5-phosphate 4-epimerase), yielding ᴅ-xylulose-5-phosphate, an intermediate in the pentose phosphate pathway. We describe here crystallographic studies of UlaE from Escherichia coli O157:H7 that complete the structural characterization of this pathway. UlaE has a triosephosphate isomerase (TIM) barrel fold and forms dimers. The active site is located at the C-terminal ends of the parallel β-strands. The enzyme binds Zn2+, which is coordinated by Glu155, Asp185, His211, and Glu251. We identified a phosphate-binding site formed by residues from the β1/α1 loop and α3′ helix in the N-terminal region. This site differs from the well-characterized phosphate-binding motif found in several TIM barrel superfamilies that is located at strands β7 and β8. The intrinsic flexibility of the active site region is reflected by two different conformations of loops forming part of the substrate-binding site. Based on computational docking of the ʟ-xylulose 5-phosphate substrate to UlaE and structural similarities of the active site of this enzyme to the active sites of other epimerases, a metal-dependent epimerization mechanism for UlaE is proposed, and Glu155 and Glu251 are implicated as catalytic residues. Mutation and activity measurements for structurally equivalent residues in related epimerases supported this mechanistic proposal. [ABSTRACT FROM AUTHOR]

Decline of estrogen is associated with high incidence of Alzheimer’s disease (AD) characterized pathologically with tau hyperphosphorylation, and glycogen synthase kinase-3β (GSK-3β) is a major tau kinase. However, the role of estrogen on GSK3β-induced tau hyperphosphorylation is elusive. Here, we treated N2a cells with wortmannin (Wort) and GF-109203X (GFX) or gene transfection to activate GSK-3β and to induce tau hyperphosphorylation and then the effects of 17β-estradiol (βE2) on tau phosphorylation and GSK-3β activity were studied. We found that βE2 could attenuate tau hyperphosphorylation at multiple AD-related sites, including Ser396/404, Thr231, Thr205, and Ser199/202, induced by Wort/GFX or transient overexpression of GSK-3β. Simultaneously, it increased the level of Ser9-phosphorylated (inactive) GSK-3β. To study whether the protective effect of βE2 on GSK-3β and tau phosphorylation involves protein kinase B (Akt), an upstream effector of GSK-3, we transiently expressed the dominant negative Akt (dnAkt) in the cells. We found that βE2 could attenuate Wort/GFX-induced GSK-3β activation and tau hyperphosphorylation with Akt-independent manner. It suggests that βE2 may arrest AD-like tau hyperphosphorylation by directly targeting GSK-3β. [ABSTRACT FROM AUTHOR]

To examine the use of acetone- or ethanol-fixed frozen tissue sections as the "gold standard" for immunohistochemical analysis, we evaluated frozen sections with various conditions of fixation and antigen retrieval (AR). Fresh human tissues were frozen in OCT. An adjacent tissue block was fixed in 10% neutral buffered formalin (NBF) and paraffin embedded (FFPE). Frozen sections were fixed by 6 protocols: acetone, ethanol, NBF (2 durations), and NBF + calcium chloride (2 durations). AR was used for all NBF-fixed sections.More than half of the antibodies (16/26 [62%]) showed immunohistochemical results indistinguishable between acetone- and NBF-fixed sections; 8 (31%) showed better immunohistochemical signals following NBF and AR; 2 gave better immunohistochemical results for acetone-fixed sections. Most cytoplasmic proteins (10/13) showed comparable immunohistochemical signals between acetone- and NBF-fixed sections. For nuclear proteins, NBF-fixed sections gave better immunohistochemical signals than did acetone-fixed sections. In most cases, NBF yielded stronger signals with less background and better morphology. The data do not support the use of acetone-fixed frozen tissue sections as the gold standard for immunohistochemical analysis. In evaluating new antibodies, a combination of acetone- and NBF-fixed frozen sections should be used, although in practice, FFPE tissue sections may serve as the standard for most antigens for immunohistochemical analysis. [ABSTRACT FROM AUTHOR]

Human estrogenic 17β-hydroxysteroid dehydrogenase (17β-HSD1), a member of the short chain dehydrogenase/reductase (SDR) family, is responsible for the biosynthesis of all active estrogens. The crystal structures of two C19-steroid ternary complexes (17β-HSD1androstanedione-NADP and 17β-HSDl-androstenedione- NADP) reveal the critical role of Leu149 in regulating the substrate specificity and provide novel insight into the different fates of a conserved glutamate residue in the estrogen-specific proteins upon the binding of the keto and hydroxyl groups of steroids. The whole NADP molecule can be unambiguously defined in the NADP binary complex, whereas both ternary complexes show that the nicotinamide moiety of NADP cannot be located in the density maps. In both ternary complexes, the expected position of carboxamide oxygen of NADP is occupied by a water molecule, which makes a bifurcated hydrogen bond with the O3 of C19-steroid and the main chain nitrogen of Val188. These results demonstrate that the hydrogen bonding interaction between the main chain amide group and the carboxamide group of NAD(P)(H) plays an important role in anchoring the nicotinamide ring to the enzyme. This finding is substantiated by structural analyses of all 33 NAD(P)(H) complexes of different SDR proteins, because 29 structures of 33 show this interaction. This common feature reveals a general mechanism among the SDR family, providing a rational basis for inhibitor design against biologically relevant SDR targets. [ABSTRACT FROM AUTHOR]

Examines the concentration dependence of the reduced viscosity of dilute polymer solution through the concept of the self-association of polymer chains in dilute solution. Relationship between the molar association constant and the hydrodynamic volume of the polymer chain in solution; Regions of the dilute polymer solution; Factors affecting the value of the Huggins coefficient of the branched polymer.

This study investigated the potential efficacy of pirarubicin (THP) in modulating rabbit conjunctival fibrosis both in vitro and in vivo and characterized the underlying mechanisms. Primary rabbit conjunctival fibroblasts (RCF) were cultured and treated with THP or mitomycin C (MMC) for 5 min, followed by assaying for cell viability, cell cycle distribution, apoptotic and autophagic pathways. The production of reactive oxygen species (ROS) and chemotaxis of macrophages by RCF were evaluated using 2′,7′-dichlorofluorescein diacetate (DCFH-DA) labeling and transwell migration assay, respectively. Limbal stem cell excision in combination with alkali burn was performed on the rabbits to establish a model of limbal deficiency and conjunctival fibro-vascular invasion. After three months, the modeled fibro-vascular tissue was excised combined with topical subconjunctival 5-min exposure to THP compared with MMC intraoperatively. The recurrence of postoperative fibrosis and the expression of apoptosis, autophagy, and inflammation markers were evaluated by immunohistochemistry. All modeled rabbits developed conjunctival fibro-vascular lesions, which were similar to human recurrent pterygium (HRP). Both THP and MMC inhibited RCF proliferation and arrested cell cycle at the G0/G1 phase. In particular, 7.5 μmol/L THP remarkably promoted RCF autophagy by upregulating the levels of Beclin 1, Atg 5/12 conjugate, and LC3B, whereas, 15 μmol/L THP significantly triggered a cascade of mitochondrial-associated RCF apoptosis. THP induced the production of ROS and enhanced the chemoattraction of macrophages by RCF. Similar to 600 μmol/L MMC, both 7.5 μmol/L and 15 μmol/L THP attenuated postoperative conjunctival fibrosis in the models; 7.5 μmol/L THP preferentially enhanced autophagy while causing fewer side effects. THP exerted its antifibrotic action by modulating autophagy in RCF, inducing cell cycle arrest, and mitochondrial-mediated apoptosis. THP at the dose of 7.5 μmol/L prevented postoperative conjunctival fibrosis in an animal model. • THP inhibited rabbit conjunctival fibroblasts proliferation and arrested cell cycle at the G0/G1 phase. • THP induced mitochondrial-mediated apoptosis and modulated autophagy in rabbit conjunctival fibroblasts. • 7.5 μmol/L THP may serve as a potential therapy for conjunctival fibrosis. • The excision of limbal stem cells resulted in the formation of conjunctival fibrovascular tissues in rabbits. [ABSTRACT FROM AUTHOR]

The article presents a chemistry research report on oxygen-deficient metal oxides supported nano-intermetallic InNi3C0.5 toward efficient CO2 hydrogenation to methanol. Topics include direct CO2 hydrogenation to methanol using renewable energy–generated hydrogen is attracting intensive attention, but qualifying catalysts represents a grand challenge; and converting CO2 into commodity chemicals is a promising approach to recycle massive quantities of CO2.

Stars of spectral type Oe are very rare. To date, only 13 Oe stars have been identified within our Galaxy. In this paper, we present six new Oe stars and four new B0e stars found in LAMOST DR5. Repeated spectral observations of the same Oe stars show some emission-line variability. The Hβ emission of TYC 4801-17-1 shows rapid V/R variation. Phase lags in the V/R ratio of TYC 4801-17-1 spectra are also seen. We found that the unusual O4.5 star RL 128 is an Oe star with variable Hα intensity and its Ca ii triplet emission appears when Hα emission reaches maximum intensity. These newly identified early-type Oe and B0e stars significantly increase the known sample. [ABSTRACT FROM AUTHOR]

A case-control study was conducted to investigate the relationship between indoor air pollution and childhood acute leukemia (AL) in Shanghai. 97 cases and 148 gender-, age-, and residencematched controls were included. Indoor air pollution was evaluated by questionnaires and quantitative measurement including 14 volatile organic compounds (VOCs) and nitrogen dioxide (NO2) in the homes of the two groups. The levels of individual VOCs, VOC families, TVOC (sum of the concentrations of the individual VOCs) and NO2 were compared between the two groups. Exposure to styrene and butyl alcohol were associated with an increased risk of childhood AL (styrene: odds ratio (OR)=2.33, 95% confidence interval (CI): 1.07-5.07; butyl alcohol: OR=2.51, 95%CI: 1.19-5.28); 4th quartile of chlorinated hydrocarbons (OR=2.52, 95%CI: 1.02-6.26) and 3rd quartile of TVOC (OR=4.03, 95%CI: 1.06-6.81) had significant higher ORs for childhood AL compared with that in the lowest quartiles. Elevated levels of individual VOCs, VOC families and TVOC were also associated with self-reported risk factors. Our findings suggest that VOCs exposure was associated with an elevated risk of childhood AL, underscore that more attention should be paid to indoor air pollution as a risk factor of childhood AL. [ABSTRACT FROM AUTHOR]

The years-long high-precision photometric data observed by Kepler satellite combining with huge amount of spectra observed by LAMOST provide a great opportunity to study the relations between surface rotation and lithium abundance of li-rich giants. In this study, we cross match the Kepler data with li-rich giants catalog from LAMOST, and obtain 619 common sources. Then we measure 36 rotation periods from the full set of 295 li-rich giants with good data quality which consists of two sub-samples. The rotation periods of 14 stars was extracted from 205 stars with evolutionary stages determined using asteroseismology, including 11 core helium-burning stars (HeBs), 2 red giant branch stars (RGBs), and 1 unclassified star. All the super lithium-rich giant stars (A (Li) > 3.3 dex) are HeBs in our sample. The remaining 90 giants do not have evolutionary stages confirmed, and in this sub-sample, 22 giants have their rotation period measured. The rotation detection rate of the former sub-sample is 6.8%, which is significantly higher than the detection rate of a large giant sample in previous studies (2.08%). With the surface rotation period measured, we confirm the relation between stellar rotation and lithium enrichment of giants. Meanwhile, we find that the less Li-enriched stars have a relatively dispersed distribution of rotation periods, and the giants with a high Li enrichment is concentrated on the rapidly rotating area, which is consistent with earlier studies. The present work also shows a jump at A (Li) ≈ 3.3 dex in the relation between rotation period and Li abundance that coincidently is the boundary between Li-rich giants and super Li-rich giants which may indicate the different mechanisms. The rotation periods of super Li-rich giants become shorter as the lithium enrichment increases. This correlation provides an evidence for the rotational induced extra-mixing mechanism responsible for Li enrichment of giants. [ABSTRACT FROM AUTHOR]

There are various treatments for cystoid macular edema (CME) secondary to retinitis pigmentosa; however, the evidence for these treatments has not been previously systematically reviewed. Our review that includes 23 studies shows that oral carbonic anhydrase inhibitors (including acetazolamide and methazolamide) and topical carbonic anhydrase inhibitors (dorzolamide and brinzolamide) are effective first-line treatments. In patients unresponsive to carbonic anhydrase inhibitor treatment, intravitreal steroids (triamcinolone acetonide and sustained-release dexamethasone implants), oral corticosteroid (deflazacort), intravitreal antivascular endothelial growth factor agents (ranibizumab and bevacizumab), grid laser photocoagulation, pars plana vitrectomy, or ketorolac were also effective in improving CME secondary to retinitis pigmentosa. Oral acetazolamide has the strongest clinical basis for treatment and was superior to topical dorzolamide. Rebound of CME was commonly seen in the long term, regardless of the choice of treatment. Oral acetazolamide should be the first-line treatment in CME secondary to retinitis pigmentosa. Topical dorzolamide is an appropriate alternative in patients intolerant to adverse effects of oral acetazolamide. More studies are required to investigate the management of rebound CME. [ABSTRACT FROM AUTHOR]