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Sediment quality caused by heavy metals was investigated in the Mirs Bay and Tolo Harbor, Hong Kong, China. Samples were collected in January and July, 2010. One-way analysis of variance showed that sediment quality variables (Fe, Zn, Mn, Pb, V, Cu, Cr, Ba, Ni and As) were significantly different (p < 0.05) among the sampling areas, whereas the average concentration of V, Eh and Ba exhibited the significant seasonal variations (p < 0.05) between January and July. The spatial pattern of heavy metals (Pb, Zn and Cu) can probably be attributed to anthropogenic and tidal flushing influence in the harbor. Both geo-accumulation index (I geo ) and enrichment factor (EF) were used to identify the metal pollution level and its related source. Pb, Zn, and Cu are considered as "polluted metal" in Tolo Harbor. Cluster analysis (CA) identified three distinct clusters with the Tolo Habor and Shatou Jiao, the inner bay and the south part of the bay. Principal component analysis (PCA) identified the spatial patterns and their affected parameters in the studying area. Results showed metals distribution in Mirs Bay and its adjacent area is principally affected by human activities such as marineculture, dumping, located mostly in Tolo Harbor and Shatou Jiao, where was closely related with anthropogenic influence. While the monitoring stations including MS13-MS16 and MS8 locating in the south part of the studying area might be corresponded to natural influence.

Due to the nature of micro-electromechanical systems, the vector magnitude (VM) activity of accelerometers varies depending on the wearing position and does not identify different levels of physical fitness. Without an appropriate energy expenditure (EE) estimation equation, bias can occur in the estimated values. We aimed to amend the EE estimation equation using heart rate reserve (HRR) parameters as the correction factor, which could be applied to athletes and non-athletes who primarily use ankle-mounted devices. Indirect calorimetry was used as the criterion measure with an accelerometer (ankle-mounted) equipped with a heart rate monitor to synchronously measure the EE of 120 healthy adults on a treadmill in four groups. Compared with ankle-mounted accelerometer outputs, when the traditional equation was modified using linear regression by combining VM with body weight and/or HRR parameters (modified models: Model A, without HRR; Model B, with HRR), both Model A (r: 0.931 to 0.972; ICC: 0.913 to 0.954) and Model B (r: 0.933 to 0.975; ICC: 0.930 to 0.959) showed the valid and reliable predictive ability for the four groups. With respect to the simplest and most reasonable mode, Model A seems to be a good choice for predicting EE when using an ankle-mounted device.

Objective: To investigate the changes of circulating proteinase 3 (PR3) in latent autoimmune diabetes mellitus in adults (LADA) patients, type 2 diabetes mellitus (T2DM) patients, obese patients without diabetes and healthy controls, and explore the value of serum PR3 in differentiating LADA and T2DM. Methods: Forty LADA patients, 29 T2DM patients, 26 obesity patients without diabetes, and 76 healthy controls were enrolled in Department of Metabolism & Endocrinology, the Second Xiangya Hospital, Central South University. Serum PR3 was detected by enzyme-linked immunosorbent assay (ELISA). The differences of serum PR3 among the four groups were compared. The correlation between serum PR3 and other metabolic indexes was analyzed. The value of serum PR3 in the differential diagnosis between LADA and T2DM was evaluated. Results: There was no significant difference in age among LADA patients, T2DM patients, obesity patients without diabetes and healthy controls [(50±13) years, (49±6) years, (49±6) years vs (47±7) years, P= 0.254], while there was significant difference in gender among the four groups (χ(2)=18.28, P< 0.001). Serum PR3 was significantly increased in LADA patients compared to the other three groups [195.4 (127.6, 288.1) μg/L vs 43.4 (30.9, 53.7) μg/L, 36.0 (29.2, 46.4) μg/L, 41.2 (30.2, 52.8) μg/L, all P< 0.01], whereas there was no significant differences among the other three groups. After adjustment for age, gender and body mass index (BMI), serum PR3 remained higher in LADA patients compared to the other three groups. Correlation analysis indicated that PR3 correlated positively with fasting and 2-hour postprandial blood glucose ( r= 0.346, r= 0.357, both P< 0.001). Receiver operating characteristic (ROC) curve showed that the cut-off value of PR3 (71.7 μg/L) for differentiating LADA and T2DM had a sensitivity of 97.5% and specificity of 89.7% and rendered an area under the curve of 0.955 (95% CI : 0.894~1.000, compared to 0.5, P< 0.01). Conclusion: Serum PR3 significantly elevated in LADA patients, and may serve as a biomarker for differentiating LADA and T2DM patients.

Photomorphogenesis is a critical plant developmental process that involves light-mediated transcriptome and histone modification changes. The transcription factor ELONGATED HYPOCOTYL5 (HY5) acts downstream of multiple families of photoreceptors to promote photomorphogenesis by regulating the expression of light-responsive genes. However, the molecular mechanism for HY5-mediated transcriptional regulation remains largely unclear. Here, we demonstrated that HY5 directly interacts with a Reduced Potassium Dependence3/Histone Deacetylase1 (HDA1)-type histone deacetylase, HDA15, both in vitro and in vivo. Phenotypic analysis revealed that HDA15 is a negative regulator of hypocotyl cell elongation under both red and far-red light conditions in Arabidopsis ( Arabidopsis thaliana ) seedlings. The enzymatic activity of HDA15 is required for inhibition of hypocotyl elongation. Furthermore, HDA15 and HY5 act interdependently in the repression of hypocotyl cell elongation in photomorphogenesis. Genome-wide transcriptome analysis revealed that HDA15 and HY5 corepress the transcription of a subset of cell wall organization and auxin signaling-related genes. In addition, HDA15 is required for the function of HY5 in the repression of genes related to hypocotyl cell elongation in Arabidopsis seedlings. Moreover, HY5 recruits HDA15 to the promoters of target genes and represses gene expression by decreasing the levels of histone H4 acetylation in a light-dependent manner. Our study revealed a key transcription regulatory node in which HY5 interacts with HDA15 involved in repressing hypocotyl cell elongation to promote photomorphogenesis., (© 2019 American Society of Plant Biologists. All Rights Reserved.)

Vinyl chloride monomer (VCM) is a confirmed carcinogen. The effects of VCM on telomeres and the gene expression of telomere complex proteins, shelterin, have not been well studied but could be of potential relevance to the carcinogenic mechanism of VCM and the health surveillance of VCM-exposed workers. A group of 241 VCM-exposed workers and 101 internal controls from the same plant in Shandong, China were recruited and quantitative polymerase chain reaction was preformed to measure relative telomere length (RTL) and gene expression of shelterin proteins. VCM cumulative exposure dose (CED) was estimated for the exposed workers. The differences in RTL and gene expression between groups were compared by Wald test fitted with robust regression. Shorter RTL was observed in VCM-exposed workers than in the controls (P < 0.001) and was related to CED of VCM. Shortened RTL was also significantly related to increasing age (P = 0.012) and high blood pressure (P = 0.056). Levels of gene expression of shelterin components in exposed workers were all lower than in controls except increased TIN2 expression, and the gene expression differences in TIN2 and POT1 among exposed and control groups were significant (P = 0.014 for TIN2 and P < 0.001 for POT1, respectively). VCM exposure is found associated with altered telomere length and gene expression of shelterin components. This provides new insights into the potential carcinogenic mechanisms of VCM and could be helpful for the health surveillance for VCM-exposed workers. Environ. Mol. Mutagen. 60:361-367, 2019. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

The technology for remediating heavy metal-contaminated soil is considerably limited because heavy metals do not undergo decomposition. Off-site reuse has emerged as the main technique for treating heavy metal-contaminated soil. Soil is the primary material in red brick making; and in the sintering procedure, heavy metals could solidify and stabilize within bricks. In this study, lead-, nickel-, and chromium-contaminated soils were collected from multiple agricultural fields. The sintering process was performed using a kiln that was for making red bricks. The sintering temperature was approximately 1000 °C. Soil and brick samples, before and after sintering, were analyzed for metal extraction concentration and binding form distribution. After sintering, the concentrations of Pb, Ni, and Cr determined through X-ray fluorescence approximated the concentrations in the soil. However, in the bricks, the bioavailability concentration of Pb, Ni, and Cr is less than 1% of that in the soil; the toxicity characteristic leaching procedure (TCLP) leaching concentration of Pb in the bricks was only 4% of that in the soil, and the leaching concentrations of Ni and Cr were lower than the detectable concentration. For the aqua regia extraction method, in the bricks, the Pb, Ni, and Cr were extracted and the concentrations accounted for 4.6%, 8.8%, and 9.4% of the concentrations in the soil, respectively. After sintering, more than 95% of Ni and Cr in the bricks were in residual fractions. The sintering process has the ability to stabilize the heavy metals in the contaminated soil.

This study examined the relationship between the expression of Ras guanyl nucleotide-releasing protein 3 (RasGRP3) and disease activity in systemic lupus erythematosus (SLE) and explored the possible mechanisms in MRL/lpr mice. We detected the expression of RasGRP3 in peripheral blood mononuclear cells (PBMCs) of SLE patients (n=26) and healthy controls (n=20) by employing RT-PCR and studied the association between the mRNA expression of RasGRP3 in PBMCs and the clinical findings. We also measured the protein level of RasGRP3 in PBMCs by Western blotting (n=10). In addition, we isolated the B cells from PBMCs with magnetic bead separation and determined the RasGRP3 expression by RT-PCR (n=10). Furthermore, we extracted spleen B cells from MRL/lpr mice and knocked down RasGRP3 by siRNA transfection to study the role of RasGRP3 in the pathway of B cell receptor (BCR) activation and the production of pro-inflammatory cytokines. Compared with healthy volunteers, the expression of RasGRP3 was significantly elevated in PBMCs and purified B cells from SLE patients. The mRNA expression of RasGRP3 in PBMCs was positively correlated with SLE disease activity index (SLEDAI). Moreover, silencing RasGRP3 could inhibit Akt and Erk1/2 activation in marginal zone (MZ) and follicular (FO) B cells of MRL/lpr mice. Additionally, the production of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), was decreased whereas activation of caspase-3 cleavage was induced in vitro . In conclusion, over-expression of RasGRP3 is associated with disease activity and might be involved in the pathogenesis of SLE., Competing Interests: None.

Most steps on the biogenesis of the mitochondrial ribosome (mitoribosome) occur near the mitochondrial DNA nucleoid, in RNA granules, which contain dedicated RNA metabolism and mitoribosome assembly factors. Here, analysis of the RNA granule proteome identified the presence of a set of small GTPases that belong to conserved families of ribosome assembly factors. We show that GTPBP10, a member of the conserved Obg family of P-loop small G proteins, is a mitochondrial protein and have used gene-editing technologies to create a HEK293T cell line KO for GTPBP10. The absence of GTPBP10 leads to attenuated mtLSU and mtSSU levels and the virtual absence of the 55S monosome, which entirely prevents mitochondrial protein synthesis. We show that a fraction of GTPBP10 cosediments with the large mitoribosome subunit and the monosome. GTPBP10 physically interacts with the 16S rRNA, but not with the 12S rRNA, and crosslinks with several mtLSU proteins. Additionally, GTPBP10 is indirectly required for efficient processing of the 12S-16S rRNA precursor transcript, which could explain the mtSSU accumulation defect. We propose that GTPBP10 primarily ensures proper mtLSU maturation and ultimately serves to coordinate mtSSU and mtLSU accumulation then providing a quality control check-point function during mtLSU assembly that minimizes premature subunit joining.

Lead is a widely existing environmental pollutant with potential carcinogenicity. To investigate the association of blood lead level (B-Pb) with potential chromosomal damage and cancer, we analyzed micronucleus (MN) frequency of peripheral blood lymphocytes (PBLs) and the methylation status of six human tumor suppressor genes (TSGs) post lead exposure. In the study, 147 lead-exposed workers were divided into two groups according to their B-Pb P 50 value, with other 50 lead-unexposed workers as a control group. The cytokinesis-blocked micronucleus (CBMN) assay was performed to detect chromosomal damage of PBLs of both lead-exposed and -unexposed workers. The methylation-specific polymerase chain reaction (MSP-PCR) was further used to examine the methylation status of six TSGs (GSTP1, hMLH1, MGMT, p14, p15, and p16). Results showed that MN frequencies of high B-Pb workers 8.1 ± 3.1‰ and low B-Pb workers 5.7 ± 2.3‰ were significantly higher than that of control group 2.8 ± 1.9‰ (P < 0.01), while the MN frequency of high B-Pb workers was also higher than that of the low B-Pb workers (P < 0.01). The MN frequency in PBLs of lead-exposed group with the methylated TSGs was significantly higher than that in PBLs with the unmethylated TSGs (P < 0.05). Notably, the CpG island methylator phenotype (CIMP) correlated with chromosome damage (P < 0.05). Additionally, workers with high B-Pb had higher chromosome damage than those with low B-Pb (P < 0.05). Taken altogether, the results suggest that lead-exposed workers with CIMP positive and high B-Pb have a higher risk of being vulnerable to tumorigenesis. Environ. Mol. Mutagen. 59:549-556, 2018. © 2018 Wiley Periodicals, Inc., (Copyright © 2018 Wiley Periodicals, Inc.)

Aim: To compare the results of axial length (AL) biometry in cataract eyes by three methods: immersion B-ultrasound (IB) biometry, immersion A-ultrasound (IA) biometry and optical low coherence reflectometry., Methods: In this prospective observational study of eyes with cataract AL measurements were performed using immersion ultrasound and optical low coherence reflectometry device. The results were evaluated using Bland-Altman analyses. The differences between both methods were assessed using the paired t -test, and its correlation was evaluated by Pearson coefficient., Results: Eighty eyes of 80 patients (39 men and 41 women) for cataract surgery were included in the study. The values of AL could be got from all 80 eyes by IB and IA, the difference of AL measurements between IA and IB was of no statistical significance ( P =0.97); the mean difference in AL measurements was -0.031 mm ( P =0.26; 95%CI, -0.09 to 0.02); linear regression showed an excellent correlation ( r =0.98, P <0.0001). Forty-five of eighty eyes with results of AL measurements, which can be obtained by three methods; the difference of AL measurements was of no statistical significance (IA vs IB, P =0.18; IA vs Lenstar, P =0.51; IB vs Lenstar, P =0.07); linear regression showed an excellent correlation (IA vs IB, r =0.99; IA vs Lenstar, r =0.96; IB vs Lenstar, r =0.96); Bland-Altman analysis also showed good agreement between the two methods [IA vs IB, 95% limits of agreement (LoA), -0.36 to 0.28 mm; IA vs Lenstar, 95% LoA, -0.65 to 0.69 mm; IB vs Lenstar, 95% LoA, -0.55 to 0.68 mm]., Conclusion: Measurements with the optical low coherence reflectometry correlated well with IB and IA. In the eyes with serious refractive medium opacity, the measurements of AL could not be achieved or existed deviations when using optical low coherence reflectometry device. Under such circumstances, we should choose IA or IB as the optimization method to obtain measurements, in order to get much more accurate results.

Background: The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast cancer remain largely unknown., Methods: In this study, the clinical impact of IDH1 expression on the progression and prognosis of breast cancer was evaluated using immunohistochemistry assay (IHC) of the corresponding tumor-adjacent normal, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissues from 309 patients with breast ductal carcinoma. The relationship between microRNA (miRNA) and IDH1 were examined by a bioinformatics approach, western blot and reporter assay. The biological functions of IDH1 were examined in breast cancer cells with IDH1 knockdown, including proliferation, migration and invasion., Results: The present findings revealed that the mRNA and protein expression levels of IDH1 were both significantly lower in breast cancer tissues than in adjacent normal tissues. A low expression level of IDH1 in breast cancer significantly correlated with advanced stage (p = 0.012), lymph node metastasis (p = 0.018), and poor disease-specific survival (DSS) (adjusted hazard ratio (AHR), 1.57, 95% confidence interval (CI), 1.08-2.30; p = 0.02). Furthermore, oncogenic miR-32 and miR-92b were identified to suppress IDH1 expression, leading to the inhibition of cell migration and invasion. We further explored whether reduced expression of IDH1 significantly increases snail expression by activating HIFα (hypoxia-inducible factor-1 alpha) and NFκB (nuclear factor kappa B) signaling. Multivariate Cox regression analysis revealed that the combination of low IDH1 and high snail expression could be an independent risk factor for shorter DSS (AHR, 2.34; 95% CI, 1.32-4.16; p = 0.004) and shorter disease-free survival (AHR, 2.50; 95% CI, 1.39-4.50; p = 0.002) in patients with breast cancer., Conclusion: Our findings revealed that a IDH1 low /Snail high molecular signature could serve as an independent biomarker for poor prognosis in breast cancer.

The Love River and Ho-Jin River, two major urban rivers in Kaohsiung City, Taiwan, are moderately to heavily polluted because different types of improperly treated wastewaters are discharged into the rivers. In this study, sediment and river water samples were collected from two rivers to investigate the river water quality and accumulation of polycyclic aromatic hydrocarbons (PAHs) in sediments. The spatial distribution, composition, and source appointment of PAHs of the sediments were examined. The impacts of PAHs on ecological system were assessed using toxic equivalence quotient (TEQ) of potentially carcinogenic PAHs (TEQ carc ) and sediment quality guidelines. The average PAHs concentrations ranged from 2161 ng/g in Love River sediment to 160 ng/g in Ho-Jin River sediment. This could be due to the fact that Love River Basin had much higher population density and pyrolytic activities. High-ring PAHs (4-6 rings) contributed to 59-90% of the total PAHs concentrations. Benzo(a)pyrene (BaP) had the highest toxic equivalence quotient (up to 188 ng TEQ/g). Moreover, the downstream sediments contained higher TEQ of total TPHs than midstream and upstream sediment samples. The PAHs were adsorbed onto the fine particles with high organic content. Results from diagnostic ratio analyses indicate that the PAHs in two urban river sediments might originate from oil/coal combustion, traffic-related emissions, and waste combustion (pyrogenic activities). Future pollution prevention and management should target the various industries, incinerators, and transportation emission in this region to reduce the PAHs pollution., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A sixth base, 5-hydroxymethylcytosine (5hmC), is formed by the oxidation of 5-methylcytosine (5mC) via the catalysis of the ten-eleven translocation (TET) protein family in cells. Expression levels of 5hmC are frequently depleted during carcinogenesis. However, the detailed mechanisms underlying the depletion of 5hmC expression in gastric cancer cells remains unclear, and further research is required. The present study examined the expression levels of 5mC and 5hmC and the expression levels of TET1 and TET2 in gastric cancer tissues using immunohistochemistry. The results revealed that 5hmC expression levels were markedly lower in gastric cancer tissues compared with corresponding adjacent normal tissues. Furthermore, a decrease in 5hmC expression levels was associated with a decrease in TET1 protein expression levels in gastric cancer tissues. The ectopic expression level of TET1 may increase the 5hmC expression level in gastric cancer cells. In addition, the results revealed that TET1 protein expression was markedly different in regards to subcellular localization, and mislocalization was significantly associated with the depletion of 5hmC expression levels in gastric cancer. Together, the results of the present study indicated that TET1 dysfunction reduces 5hmC expression levels, and this phenomenon may serve a crucial role in gastric cancer progression.

Dysregulation of pericellular proteolysis is often required for tumor invasion and cancer progression. It has been shown that down-regulation of hepatocyte growth factor activator inhibitor-2 (HAI-2) results in activation of matriptase (a membrane-anchored serine protease), human prostate cancer cell motility and tumor growth. In this study, we further characterized if HAI-2 was a cognate inhibitor for matriptase and identified which Kunitz domain of HAI-2 was required for inhibiting matriptase and human prostate cancer cell motility. Our results show that HAI-2 overexpression suppressed matriptase-induced prostate cancer cell motility. We demonstrate that HAI-2 interacts with matriptase on cell surface and inhibits matriptase proteolytic activity. Moreover, cellular HAI-2 harnesses its Kunitz domain 1 (KD1) to inhibit matriptase activation and prostate cancer cell motility although recombinant KD1 and KD2 of HAI-2 both show an inhibitory activity and interaction with matriptase protease domain. The results together indicate that HAI-2 is a cognate inhibitor of matriptase, and KD1 of HAI-2 plays a major role in the inhibition of cellular matritptase activation as well as human prostate cancer invasion.

New Mg-containing antimonide Zintl phases, Sr 14 MgSb 11 and Eu 14 MgSb 11 , were synthesized from high-temperature solid-state reactions in Ta tubes at 1323 K. Their structures can be viewed as derived from the Ca 14 AlSb 11 structure type, which adopt the tetragonal space group I4 1 /acd (No. 142, Z = 8) with the cell parameters of a = 17.5691(14)/17.3442(11) Å and c = 23.399(4)/22.981(3) Å for the Sr- and Eu-containing compounds, respectively. The corresponding thermoelectric properties were probed, which demonstrated high potential of these compounds as new thermoelectrics for their very low thermal conductivity and moderate Seebeck coefficient. Magnetism studies and theoretical calculations were conducted as well to better understand the structure-and-property correlation of these materials.

Background: This phase 3 trial is the first to evaluate the efficacy and safety of treatment with the systemic TNF-α inhibitor, adalimumab, for Chinese patients with moderate-to-severe plaque psoriasis., Methods: In the 12-week, double-blind, placebo-controlled Period A, patients were randomized 4 : 1 to receive adalimumab 40 mg every-other-week (following a single 80 mg dose), or placebo every-other-week. In the subsequent 12-week, open-label, Period B, all patients received adalimumab 40 mg every-other-week starting at week 13, following a single, blinded dose at week 12 of adalimumab 80 mg or matching placebo (for patients receiving placebo or adalimumab in Period A respectively). In Period A, efficacy was analysed for all randomized patients and safety for all patients receiving ≥1 dose of the study drug., Results: For the 425 patients in this study (87 placebo; 338 adalimumab), a higher percentage randomized to adalimumab achieved the primary endpoint of ≥75% improvement from baseline in PASI score (PASI 75) at week 12: placebo 11.5% (10/87); adalimumab 77.8% (263/338; P < 0.001). Physician's Global Assessment of clear to minimal was achieved at week 12 by 14.9% placebo (13/87) and 80.5% adalimumab (272/338; P < 0.001). For patients who received adalimumab at any time during the study (All-adalimumab Population), treatment-emergent adverse events (AEs) were reported by 63.4%; the most common was upper respiratory infection (16.1%). Serious AEs were reported by 3.5% of the All-adalimumab Population, and serious infectious AEs by 1.2%, which include lung infection, pneumonia and tuberculosis [2 (0.5%) patients each]. There was one death (chronic heart failure)., Conclusion: In these Chinese patients with moderate-to-severe psoriasis, a significantly greater percentage treated with adalimumab compared with placebo achieved efficacy endpoints at week 12 and efficacy was sustained to week 24. Safety results were consistent with the known adalimumab safety profile; no new safety signals were identified in the 24 weeks of treatment., (© 2016 The Authors. Journal of European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venerology.)

Coastal water quality and trophic status are subject to intensive environmental stress induced by human activities and climate change. Quarterly cruises were conducted to identify environmental characteristics in Daya Bay in 2013. Water quality is spatially and temporally dynamic in the bay. Cluster analysis (CA) groups 12 monitoring stations into two clusters. Cluster I consists of stations (S1, S2, S4-S7, S9, and S12) located in the central, eastern, and southern parts of the bay, representing less polluted regions. Cluster II includes stations (S3, S8, S10, and S11) located in the western and northern parts of the bay, indicating the highly polluted regions receiving a high amount of wastewater and freshwater discharge. Principal component analysis (PCA) identified that water quality experience seasonal change (summer, winter, and spring-autumn seasons) because of two monsoons in the study area. Eutrophication in the bay is graded as high by Assessment of Estuarine Trophic Status (ASSETS)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The isocitrate dehydrogenase (IDH) family of enzymes comprises of the key functional metabolic enzymes in the Krebs cycle that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG). α-KG acts as a cofactor in the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). However, the relationship between 5hmC and IDH in gastric cancer remains unclear. Our study revealed that the 5hmC level was substantially lower and 5mC level was slightly higher in gastric cancer tissues; however, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) levels did not change significantly in these tissues. We further examined the expression levels of IDH1 and IDH2 in gastric cancer tissues and observed that IDH2 levels were significantly lower in gastric cancer tissues than in the adjacent normal tissues. The ectopic expression of IDH2 can increase 5hmC levels in gastric cancer cells. In conclusion, our results suggested that IDH2 dysfunction is involved in 5hmC depletion during gastric cancer progression., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Non-functioning pituitary adenomas (NFPAs) are usually macroadenomas and display invasion into surrounding tissues. The treatment for invasive NFPAs is still challenging. This study describes the differential patterns of gene expression between invasive and non-invasive NFPAs and identifies novel biomarkers involved in invasion of NFPAs for diagnosis and treatment. Using gene microarray technology, we examined the gene expression profile and found 1160 differentially expressed messenger RNA (mRNA) between invasive and non-invasive NFPAs. Then, we examined the protein profile by liquid chromatography tandem mass spectrometry (LC-MS/MS) and found 433 differentially expressed proteins between invasive and non-invasive NFPAs. Subsequently, we integrated the proteomics and transcriptomics datasets and identified 29 common changed molecules. Through bioinformatics analysis using Ingenuity Pathway Analysis (IPA) software, we showed that the 29 molecules were enriched in 25 canonical signaling pathways, 25 molecular and cellular functions, and 2 networks. Eight genes were identified involved in the invasion function by the molecular and cellular functions analysis, including CAT, CLU, CHGA, EZR, KRT8, LIMA1, SH3GLB2 and SLC2A1. Furthermore, we validated the decreased CHGA expression and increased CLU expression in invasive NFPAs by qRT-PCR and Western blot. Our study demonstrated that integration of proteomics and transcriptomics could prove advantageous for accelerating tumor biomarker discovery and CHGA and CLU might be important novel biomarkers and therapeutic targets for invasion of NFPAs.

Background: Acne vulgaris affects up to 54% of Chinese adolescents. Combination therapy has become the recommended standard of care for acne., Objective: The aim of this study was to compare the efficacy and safety of clindamycin (1%) and benzoyl peroxide (5%) (CDP/BPO) gel once daily vs. clindamycin (1%) (CDP) monotherapy gel twice daily in Chinese patients with mild to moderate acne., Methods: 1020 patients (aged 12-45 years) with mild to moderate acne were randomized (1 : 1); 1016 patients were treated with CDP/BPO (n = 500) or CDP (n = 516) for a 12-week treatment period. Efficacy assessments were performed at baseline, and at weeks 1, 2, 4, 8 and 12; and primarily included change in total lesion count (inflammatory and non-inflammatory lesions), and proportion of patients with a minimum 2-grade improvement in Investigator's Static Global Assessment (ISGA) score. Patient safety and local tolerability were also evaluated., Results: Patients in CDP/BPO group showed a greater per cent reduction in total lesion count compared with patients in CDP group at week 12 (delta = -0.05; 95% CI = -0.09, -0.02; P = 0.003); statistically significant reduction in lesion count was noted as early as week 1 and continued through week 12. A greater proportion of patients in CDP/BPO group showed a ≥2-grade improvement in ISGA score at week 12 compared with CDP group (30.2% vs. 22.7%; P = 0.018). Overall, the incidence of adverse events (AEs) was higher in the CDP/BPO group (14.4%) than in the CDP group (7.9%); the most commonly reported events were generally related to application site reactions (erythema, pruritus and swelling). Incidence of drug-related AEs was 8.6% in CDP/BPO group and 1.2% in CDP group. Both groups showed trends towards reduction in investigator and subject rated local tolerability scores., Conclusion: CDP/BPO gel demonstrated superior efficacy over CDP gel along with acceptable safety and tolerability in Chinese patients with mild to moderate acne., Gov Number: NCT01915732., (© 2016 European Academy of Dermatology and Venereology.)

MicroRNAs (miRNAs) are short noncoding RNAs derived from the 3' and 5' ends of the same precursor. However, the biological function and mechanism of miRNA arm expression preference remain unclear in breast cancer. We found significant decreases in the expression levels of miR-193a-5p but no significant differences in those of miR-193a-3p in breast cancer. MiR-193a-3p suppressed breast cancer cell growth and migration and invasion abilities, whereas miR-193a-5p suppressed cell growth but did not influence cell motility. Furthermore, NLN and CCND1, PLAU, and SEPN1 were directly targeted by miR-193a-5p and miR-193a-3p, respectively, in breast cancer cells. The endogenous levels of miR-193a-5p and miR-193a-3p were significantly increased by transfecting breast cancer cells with the 3'UTR of their direct targets. Comprehensive analysis of The Cancer Genome Atlas database revealed significant differences in the arm expression preferences of several miRNAs between breast cancer and adjacent normal tissues. Our results collectively indicate that the arm expression preference phenomenon may be attributable to the target gene amount during breast cancer progression. The miRNA arm expression preference may be a means of modulating miRNA function, further complicating the mRNA regulatory network. Our findings provide a new insight into miRNA regulation and an application for breast cancer therapy.

Zn1-xMgxO films with x = 0.04-0.50 grown on MgO (100) substrates by molecular beam epitaxy retain the rocksalt (rs) crystal structure and grow epitaxially for x ≥ 0.17. In addition, the rs-ZnO epilayer is observed to be stable up to a thickness of 5 nm and also in a ZnO/MgO superlattice sample. However, a portion of the superlattice has transformed to wurtzite (wz)-structure islands in a self-accommodated manner during growth. The transformation is a combination of a Bain distortion, an in-plane rotation of 14.5°, and a Peierls distortion, resulting in an orientation relationship of (100)rs//(101̄0)wz and 〈011〉rs ∼//〈1̄21̄3〉wz. In such a manner, the volume expansion is only necessary along the growth direction and the in-plane strains can be minimized. A negative pressure generated during the transformation of ZnO stabilizes the MgO into a wurtzite structure.

Lipooligosacharide (LOS) of Neisseria gonorrhoeae (gonococci, GC) is involved in the interaction of GC with host cells. Deletion of the alpha-oligosaccharide (alpha-OS) moiety of LOS (lgtF mutant) significantly impairs invasion of GC into epithelial cell lines. GC opacity (Opa) proteins, such as OpaI, mediate phagocytosis and stimulate chemiluminescence responses in neutrophils in part through interaction with members of the carcinoembryonic antigen (CEA) family, which includes CEACAM3 (CD66d), a human neutrophil specific receptor for phagocytosis of bacteria. In the present work, we examined the effects of OpaI-expressing lgtF mutant on phagocytosis by HeLa-CEACAM3 cells and chemiluminescence responses in neutrophils. The results showed that lgtF mutant even expressing OpaI completely lost the ability to promote either phagocytosis mediated by CEACAM3 interaction in HeLa cells or chemiluminescence responses in neutrophils. These data indicated that Opa proteins in the lgtF mutant, which might result from the conformational change, cannot be functional.

Background: Primary immune thrombocytopenic purpura (pITP) is defined as isolated autoimmune thrombocytopenia with idiopathic low platelet count, normal bone marrow, and unexplained causes of thrombocytopenia. Currently there is no definite criterion for ITP diagnosis., Methods: We conducted proteomic screen of patients with pITP, secondary immune thrombocytopenia (sITP), and healthy controls using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The proteomic profiles were obtained from platelet lysate samples of 82 healthy adult controls, 64 pITP, and 70 sITP patients, from which we screened marker proteins with significant differences, and constructed a diagnosis model using the artificial neural network (ANN) technique., Results: We identified 6 marker proteins in the platelet lysates of pITP patients. This diagnosis method differentiated pITP patients from sITP effectively with a sensitivity of 96.9% (31/32), a specificity of 71.0% (54/76), and the area under the ROC curve of 0.864 in the training set, and a sensitivity of 87.5% (28/32), a specificity of 69.7% (53/76), and a positive predictive value of 75.0% (81/108) in the test set., Conclusion: The artificial neural network model based on platelet protein profiling established a potential pITP diagnosis platform., (Copyright © 2016. Published by Elsevier B.V.)

Transforming growth factor (TGF)-β signaling plays an important role in the pathogenesis of psoriasis. CD109, a novel TGF-β co-receptor, which inhibits TGF-β signaling by enhancing Smad7-dependent degradation of TGF-β type I receptor (TGF-β RI), is abnormally expressed in psoriasis. To date, the expression of Smad7 and the correlation between CD109 and Smad7 expression in psoriasis have not been fully elucidated. This study was designed to investigate the expression and the correlation of CD109 and TGF-β signaling associated proteins in psoriasis and their roles in the pathogenesis of psoriasis. Thirty-two psoriasis specimens were subjected to immunohistochemical staining for CD109, Smad7, TGF-β RI and Ki67. Ten normal skin (NS) specimens served as controls. The positive expression rate (% positive cells) of Smad7 and Ki67 in psoriasis was significantly higher than in NS (62.6%±19.9% vs. 17.2%±4.4%, and 50.7%±14.3% vs. 19.5%±3.2%, respectively, P<0.001), and the expression levels of CD109 and TGF-β RI were reduced significantly in psoriasis as compared with NS (8.1%±6.7% vs. 35.8%±6.7% and 27.3%±3.4% vs. 3.0%±3.4%, respectively, P<0.001). There were significantly negative correlations between CD109 and Smad7 (r=-0.831, P<0.01). These findings indicated that CD109 might play a certain role in the pathogenesis of psoriasis. Lower expression of CD109 and TGF-β RI was highly correlated with higher expression of Smad7 and Ki67, suggesting that CD109 may induce the pathogenesis of psoriasis through Smad7-mediated degradation of TGF-β RI, and lead to the termination of TGF-β signaling.

Piperlongumine (PLGM) was considered as an anti-cancer agent since it was involved in suppressing of many types of cancer. To investigate the functions and mechanisms of PLGM on drug resistance reversal in human retinoblastoma cell lines, drug resistance cell lines HXO-RB44/VCR and SO-Rb50/CBP were established. We found that after treatment with PLGM, drug sensitivity and apoptosis rate of these drug resistance cancer cells were improved, cell cycle was arrested, the expressions of P-gp, MDR1, MRP1, Top-II, GST-π, Survivin, Bcl-2, CDK1, ABCB1 and ABCG1 was decreased, while the activities of caspase-3/8 and intracellular content of Rh-123 was increased. Furthermore, the activities of PI3K/AKT and PKCζ pathways were suppressed following PLGM treatment. Therefore, this study suggests that PLGM could reverse the drug resistance of human retinoblastoma cell lines HXO-RB44/VCR and SO-Rb50/CBP. This drug resistance reversing effect might exert via PI3K/AKT and PKCζ pathways.

Human mitochondrial ribosomes are specialized in the synthesis of 13 proteins, which are fundamental components of the oxidative phosphorylation system. The pathway of mitoribosome biogenesis, the compartmentalization of the process, and factors involved remain largely unknown. Here, we have identified the DEAD-box protein DDX28 as an RNA granule component essential for the biogenesis of the mitoribosome large subunit (mt-LSU). DDX28 interacts with the 16S rRNA and the mt-LSU. RNAi-mediated DDX28 silencing in HEK293T cells does not affect mitochondrial mRNA stability or 16S rRNA processing or modification. However, it leads to reduced levels of 16S rRNA and mt-LSU proteins, impaired mt-LSU assembly, deeply attenuated mitochondrial protein synthesis, and consequent failure to assemble oxidative phosphorylation complexes. Our findings identify DDX28 as essential during the early stages of mitoribosome mt-LSU biogenesis, a process that takes place mainly near the mitochondrial nucleoids, in the compartment defined by the RNA granules., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

The ribosome is a structurally and functionally conserved macromolecular machine universally responsible for catalyzing protein synthesis. Within eukaryotic cells, mitochondria contain their own ribosomes (mitoribosomes), which synthesize a handful of proteins, all essential for the biogenesis of the oxidative phosphorylation system. High-resolution cryo-EM structures of the yeast, porcine and human mitoribosomal subunits and of the entire human mitoribosome have uncovered a wealth of new information to illustrate their evolutionary divergence from their bacterial ancestors and their adaptation to synthesis of highly hydrophobic membrane proteins. With such structural data becoming available, one of the most important remaining questions is that of the mitoribosome assembly pathway and factors involved. The regulation of mitoribosome biogenesis is paramount to mitochondrial respiration, and thus to cell viability, growth and differentiation. Moreover, mutations affecting the rRNA and protein components produce severe human mitochondrial disorders. Despite its biological and biomedical significance, knowledge on mitoribosome biogenesis and its deviations from the much-studied bacterial ribosome assembly processes is scarce, especially the order of rRNA processing and assembly events and the regulatory factors required to achieve fully functional particles. This article focuses on summarizing the current available information on mitoribosome assembly pathway, factors that form the mitoribosome assembly machinery, and the effect of defective mitoribosome assembly on human health.

Endothelin-1 (ET-1) is a small 21-amino acid peptide that is known to exert diverse biological effects on a wide variety of tissues and cell types through its own receptors. The ET-1-ETRA axis is frequently dysfunctional in numerous types of carcinomas, and contributes to the promotion of cell growth and migration. microRNAs (miRNAs) are small non-coding RNAs that play a critical role in carcinogenesis through mRNA degradation or the translational inhibition of cancer-associated protein-coding genes. However, the role of ET-1 and the relationship between ET-1 and miRNAs in gastric cancer remain unknown. Results of the analysis of the database of The Cancer Genome Atlas (TCGA) revealed that ET-1 is significantly overexpressed in gastric cancer cells when compared with its expression in adjacent normal cells. Exogenous ET-1 significantly enhanced gastric cancer cell proliferation, implying that ET-1 plays an oncogenic role in gastric cancer carcinogenesis. Using a luciferase reporter assay we showed that 18 miRNA candidates had a significant silencing effect on ET-1 expression by up to 20% in HEK293T cells. Among them, 5 miRNAs (miR-1, miR-101, miR-125A, miR-144 and let-7c) were shown to be involved in ET-1 silencing through post-transcriptional modulation in gastric cancer. Our data also revealed that DNA hypermethylation contributes to the silenced miR-1 expression in gastric cancer cells. The ectopic expression of miR-1 significantly inhibited AGS cell proliferation by suppressing ET-1 expression. Overall, our study revealed that ET-1 overexpression may be due to DNA hypermethylation resulting in the silencing of miR-1 expression in gastric cancer cells. In addition, we identified several miRNAs as potential modulators for ET-1 in gastric cancer, which may be used as targets for gastric cancer therapy.

To confirm the existence of the tight junction (TJ) in middle intestine and obtain the genetic information of Claudin-3, Claudin-15a, Claudinb and Claudinc of grass carp, we observed the physical structure of TJ by transmission electron microscopy and cloned the partial cDNAs of the four Claudins using reverse transcriptase PCR technique. The four partial cDNAs consist of 1,261, 490, 776 and 662 bp encoded 131, 150, 195 and 171 amino acids, respectively. Homology analysis showed that the grass carp Claudin shared high homology with other teleost species, especially with Danio rerio and Carassius auratus. Multi-alignments of the four Claudin amino acid sequences have seen the two conserved cysteines existing in the first extracellular loop of Claudin-15a, Claudinb and Claudinc, and the sequence diversity of the four Claudins mainly lies within the C-terminal tails, which usually end with the -Y-V motif, except the -F-V motif in Claudinb. Tissue distributions of the four Claudins were measured by applying quantitative real-time PCR technique. Results showed that Claudin-3 was mainly expressed in liver and middle intestine and Claudinb was ubiquitously expressed with a higher expression in middle intestine while Claudin-15a and Claudinc were mainly expressed in middle intestine. Our study revealed the existence of the TJ in the middle intestinal and obtained the genetic information of Claudin-3, Claudin-15a, Claudinb and Claudinc of grass carp, aiming to found the molecular biology basis for the further study of the intestinal barrier function of grass carp.

Dysregulation of cell surface proteolysis has been strongly implicated in tumorigenicity and metastasis. In this study, we delineated the role of hepatocyte growth factor activator inhibitor-2 (HAI-2) in prostate cancer (PCa) cell migration, invasion, tumorigenicity and metastasis using a human PCa progression model (103E, N1, and N2 cells) and xenograft models. N1 and N2 cells were established through serial intraprostatic propagation of 103E human PCa cells and isolation of the metastatic cells from nearby lymph nodes. The invasion capability of these cells was revealed to gradually increase throughout the serial isolations (103E

In this study, microcosm and pilot-scale experiments were performed to investigate the capability and effectiveness of Pseudomonas mendocina NSYSU (P. mendocina NSYSU) on the bioremediation of octachlorodibenzo-p-dioxin (OCDD)-contaminated soils. The objectives were to evaluate the (1) characteristics of P. mendocina NSYSU, (2) feasibility of enhancing OCDD biodegradation with the addition of P. mendocina NSYSU and lecithin, and (3) variation in microbial diversity and genes responsible for the dechlorination of OCDD. P. mendocina NSYSU was inhibited when salinity was higher than 7%, and it could biodegrade OCDD under reductive dechlorinating conditions. Lecithin could serve as the solubilization agent causing the enhanced solubilization and dechlorination of OCDD. Up to 71 and 62% of OCDD could be degraded after 65 days of incubation under anaerobic conditions with and without the addition of lecithin, respectively. Decreased OCDD concentrations caused significant increase in microbial diversity. Results from the pilot-scale study show that up to 75% of OCDD could be degraded after a 2.5-month operational period with lecithin addition. Results from the gene analyses show that two genes encoding the extradiol/intradiol ring-cleavage dioxygenase and five genes encoding the hydrolase in P. mendocina NSYSU were identified and played important roles in OCDD degradation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

As one of the most serious types of psoriasis, pathogenesis of erythrodermic psoriasis (EP) is unclear so far. In this study, we aimed to detect the levels of Th1/Th2 cytokine-associated transcription factors and T-lymphocyte clone in peripheral blood mononuclear cells (PBMCs) derived from EP patients, and gene expression level of T-bet/GATA-3 in skin lesion. The potential role of Th1/Th2 reaction pattern played in the pathogenesis of EP was also discussed. Serum levels of IFN-γ, IL-2, IL-4 and IL-10 were quantified by ELISA among 16 EP patients, 20 psoriasis vulgaris (PV) patients and 15 healthy controls. The expression levels of T-bet/GATA-3 in the skin lesion and PBMCs were examined by real-time qPCR. The ratio of Th1/Th2 was measured by flow cytometry. The levels of IFN-γ, IL-2, IL-4 and IL-10 were higher in EP patients than in the healthy controls. The levels of IL-4 and IL-10 were 69.44±11.45 and 12.62±4.57 pg/mL, respectively, in EP patients, significantly higher than those in PV patients and healthy controls (P<0.05). Flow cytometry revealed the levels of both Th1 and Th2 in PBMCs from EP patients were higher than those in healthy controls, and the Th1/Th2 ratio was dramatically lower than in PV patients (P<0.01). The ratios of IFN-γ/IL-4 and T-bet/GATA-3 in EP patients were both less than 1.0, suggesting a reversal when compared with the other two groups. Our study indicated that the EP patients exerted a Th1/Th2 bidirectional response pattern, and the balance of Th cell subsets inclines to Th2, which might be one of the important mechanisms of EP pathogenesis.

Background and Objective: Photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) offers promising results for the treatment of condyloma acuminatum. However, patients have to dwell with pain to benefit from this otherwise effective and safe "off-label" treatment modality. Several techniques have been explored to control ALA-PDT-induced pain, but the desperate search for a universally accepted method is still ongoing. This study compares the two-step irradiance approach with single-dose administration of 100 mg tramadol sustained-release tablets for pain induced by ALA-PDT of condyloma acuminatum in Chinese patients., Patients and Methods: Adult Chinese patients with condyloma acuminatum were enrolled in a randomized comparative study. Pain levels were compared using the Numeric Rating Scale (NRS) at pre-defined assessment points during and after irradiation., Results: The pain was dominated by characteristics such as burning and pricking and was almost always local and superficial., During Irradiation: The median pain scores were lower in the two-step irradiance group at 1 minute (U = 621.5, P = 0.002) but higher at 20 minutes (U = 585.5, P = 0.002). The median pain scores between the two groups did not differ significantly at other assessment points. The pain was moderate in both groups and peaked earlier in the analgesics group (median: 5 minutes) but later in the two-step irradiance group (median: 15 minutes)., After Irradiation: The pain was generally mild. The median pain scores were equal at each assessment point, except at 3 hours where the median was lower in the analgesics group (1.0) as compared with the two-step irradiance group (2.0) (U = 725.0, P = 0.056)., Conclusions: Pain in the two-step irradiance protocol is irradiance-dependent. The two-step irradiance approach produces significant benefits over analgesics during the initial stages of therapy but analgesics offer significant benefits thereafter. There are potential benefits of combining the two approaches in minimizing ALA-PDT-induced pain., (© 2014 Wiley Periodicals, Inc.)

The deubiquitinating enzyme ubiquitin specific peptidase 15 (USP15) is regarded as a regulator of TGFβ signaling pathway. This process depends on Smad7, the inhibitory factor of the TGFβ signal, and type I TGFβ receptor (TβR-I), one of the receptors of TGFβ. The expression level of USP15 seems to play vital roles in the pathogenesis of many neoplasms, but so far there has been no report about USP15 in psoriasis. In this study, immunohistochemical staining of USP15, TβR-I and Smad7 was performed in 30 paraffin-embedded psoriasis specimens and 10 normal specimens to investigate the expression of USP15, TβR-I and Smad7 in psoriasis and to explore the relevance among them. And USP15 small interfering RNA (USP15 siRNA) was used to transfect Hacat cells to detect the mRNA expression of TβR-I and Smad7. Of 30 cases of psoriasis in active stage, 28, 24 and 26 cases were positive for USP15, TβR-I and Smad7 staining, respectively. The positive rates of USP15 and Smad7 were significantly higher in psoriasis specimens than in normal skin specimens (44.1%±26.0% vs. 6.1%±6.6%, 47.2%±27.1% vs. 6.6%±7.1%), and positive rate of TβR-I (20.3%±22.2%) in psoriasis was lower than that in normal skin specimens (46.7%±18.2%). There was a significant positive correlation between USP15 and Smad7 expression, and significant negative correlations between USP15 and TβR-expression, an I d between TβR- and Smad7 expression I in psoriasis. After transfection of USP15 siRNA in Hacat cells, the expression of TβR-mRNA was up I -regulated and that of Smad7 was down-regulated. It is concluded that USP15 may play a role in the pathogenesis of psoriasis through regulating the TβR-I/Smad7 pathway and there may be other cell signaling pathways interacting with USP15 to take part in the development of psoriasis.

Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined. As compared with the empty-vector group, cell proliferation was slowed down, and the growth inhibition rates were 38.9% in A375 cells and 38.4% in MMRU cells after transfection. In addition, cell invasion capability was also inhibited, with a reduction of 62.2% in A375 cells and 54.3% in MMRU cells. The percentage of apoptotic cells was found to increase. Meanwhile, in both cell lines, secreted protein acidic and rich in cysteine (SPARC) levels were down-regulated together with inhibition of its upstream signaling molecule, NF-κB. Thus, the current results suggested that down-regulated expression of ET3 attenuates the malignant behaviors of human melanoma cells partially by decreasing the expression of SPARC and NF-κB.

The rs10954213 polymorphism and the haplotype diversity in interferon regulatory factor 5 (IRF5) play a special role in systemic lupus erythematosus (SLE) but with inconclusive results. We conducted a meta-analysis integrating case-control and haplotype variant studies in multiple ethnic populations to clearly discern the effect of these two variants on SLE. Eleven studies on the relation between rs10954213 polymorpisms in IRF5 and SLE were included and we selected a random effect model to calculate the pooled odds ratios (ORs) and the corresponding 95% confidence interval (95% CI). A total of 6982 cases and 8077 controls were involved in the meta-analysis. The pooled results indicated that A allele was significantly associated with increased risk of SLE as compared with the IRF5 rs10954213 G allele (A vs. G, P<0.00001) in all subjects. The same pattern of the results was also obtained in the European, African American, and Latin American. Asian population had a much lower prevalence of the A allele (49.1%) than any other population studied, and Europeans had the highest frequency of the IRF5 rs10954213 A allele (62.1%). The significant association of increased SLE risk and TCA haplotype was indicated in the contrast of TCA vs. TTA as the pooled OR was 2.14 (P=0.002). The same result was also found in the contrast of TCA vs. TTG as the pooled OR was 1.45 (P=0.004). This meta-analysis suggests that the A allele of rs10954213 and TCA haplotype (rs2004640-rs2070197-rs10954213) in IRF5 is associated with the increased risk of SLE in different ethnic groups, and its prevalence is ethnicity dependent.

Background: MicroRNAs (miRNAs) are short noncoding RNAs (approximately 22 nucleotides in length) that play important roles in colorectal cancer (CRC) progression through silencing gene expression. Numerous dysregulated miRNAs simultaneously participate in the process of colon cancer development. However, the detailed mechanisms and biological functions of co-expressed miRNA in colorectal carcinogenesis have yet to be fully elucidated., Results: The objective of this study was to identify the dysfunctional miRNAs and their target mRNAs using a wet-lab experimental and dry-lab bioinformatics approach. The differentially expressed miRNA candidates were identified from 2 miRNA profiles, and were confirmed in CRC clinical samples using reported target genes of dysfunctional miRNAs to perform functional pathway enrichment analysis. Potential target gene candidates were predicted by an in silico search, and their expression levels between normal and colorectal tumor tissues were further analyzed using real-time polymerase chain reaction (RT-PCR)., Conclusion: Fifteen dysfunctional miRNAs were engaged in metastasis-associated pathways through comodulating 7 target genes, which were identified by using a multi-step approach. The roles of these candidate genes are worth further exploration in the progression of colon cancer, and could potentially be targets in future therapy.

The effects of polycyclic aromatic hydrocarbon (PAH) (pyrene) on superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase, peroxidase, malondialdehyde (MDA) and proline were studied in leaves, stems and roots of Bruguiera gymnorrhiza. The results showed that the responses of enzymatic and non-enzymatic antioxidants varied significantly among the three tissues studied. The activities of antioxidant enzymes in PAH-treated stems and roots fluctuated in different stress levels compared to the controls, while the antioxidant enzymes such as SOD, APX in leaves increased when stressed by PAH with a significant positive relation between PAH and leaf SOD or APX activity. Low PAH treatments could also stimulate proline in leaves and stems. MDA content was obviously accumulated in stems and roots under PAH stress while decreased in leaves, indicating that the increased antioxidant enzymes in leaves may partly alleviate lipid peroxidation. For pollution monitoring purpose, SOD and APX in leaves may be potential biomarkers of PAH pollution in intertidal estuaries.

Effects of N deficiency and salinity on root anatomy, permeability and metal (Pb, Zn and Cu) translocation and tolerance were investigated using mangrove seedlings of Rhizophora stylosa. The results showed that salt could directly reduce radial oxygen loss (ROL) by stimulation of lignification within exodermis. N deficiency, oppositely, would reduce lignification. Such an alteration in root permeability may also influence metal tolerance by plants. The data indicated that a moderate salinity could stimulate a lignified exodermis that delayed the entry of metals into the roots and thereby contributed to a higher metal tolerance, while N deficiency would aggravate metal toxicity. The results from sand pot trail further confirmed this issue. This study provides a barrier property of the exodermis in dealing with environments. The plasticity of root anatomy is likely an adaptive strategy to regulate the fluxes of gases, nutrients and toxins at root-soil interface., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Numerous molecular events have been associated with the development of malignant melanoma (MM). The cellular FLICE-like inhibitory protein (c-FLIP) was originally identified as an inhibitor of death-receptor signalling through competition with FADD-like interleukin-1β-converting enzyme (FLICE; also known as caspase-8) for recruitment to the FAS-associated death domain (FADD), and it has been suggested recently that c-FLIP is required for the survival and proliferation of various cell types. Aim.  To investigate the relationship of c-FLIP expression with the clinicopathological features of MM., Methods: Immunohistochemical staining with anti-c-FLIP antibody was performed on tissue samples taken from 77 MMs and 20 naevi. The proliferative cells were visualized by staining with Ki-67 antibody. Annexin V-propidium iodide labelling, a marker for chromatin condensation, was performed to observe the rate of cell apoptosis by flow cytometry., Results: Expression of c-FLIP was increased in MM tissue compared with the matched pigmented naevi. The c-FLIP expression was significantly associated with the histological type and Clark level of MM, and correlated strongly with the Ki-67 labelling index. Downregulation of c-FLIP might increase apoptosis in MM cell lines., Conclusions: c-FLIP might play an important role in the obtaining of aggressive biological behaviours and be useful in predicting prognosis of patients with MM., (© The Author(s). CED © 2011 British Association of Dermatologists.)

Fifty-eight sediment samples were collected in 2009 from the bottom of river mouths near Kaohsiung Harbor (Taiwan) and the harbor channel for the analyses of polycyclic aromatic hydrocarbons (PAHs) using gas chromatography-mass spectrometry (GC-MS). Concentrations of total PAHs varied from 39 to 30,521 ng g(-1) (dry weight); samples collected from the mouths of Love River, Canon River, Jen-Gen River, and Salt River showed the highest PAHs concentrations. This indicates that the major sources of sediment PAHs come from those polluted urban rivers and the harbor channel. In samples collected from the Salt River mouth, approximately 43% of the PAHs are identified as PAHs with 2 or 3 rings. However, samples collected from other locations contain predominantly PAHs with 4 rings (32 to 42%) or 5 and 6 rings (36 to 44%). Emissions from traffic-related sources and waste incineration contribute to the majority of PAHs found in most channel and river mouth sediments. However, coal/oil combustion is the main cause of high concentrations of PAHs observed in the Salt River mouth sediments. Principal component analyses with multivariate linear regression (PCA/MLR) have been used to further quantify the source contributions, and the results show that the contributions of coal/oil combustion, traffic-related and waste incineration are 37%, 33% and 30%, respectively.

The c-Jun amino-terminal kinase (JNK) pathway seems to play important roles in the pathogenesis of several tumors, but its significance in extramammary Paget disease (EMPD) has not been investigated yet. The purpose of the study was to investigate the potential contribution of the JNK-associated molecules, such as hematopoietic progenitor kinase 1 (HPK1), mitogen-activated protein/extracellular signal-related protein kinase kinase kinase1 (MEKK1), transforming growth factor-β activated kinase 1 (TAK1), and phosphomitogen-activated protein kinase kinase 4 (p-MKK4) to the development of EMPD. Thirty-five paraffin-embedded EMPD specimens were subjected to immunohistochemical staining for HPK1, MEKK1, TAK1, and p-MKK4. All the 35 EMPD, including 13 dermal invasive EMPD and 2 lymph node metastasis, showed cytoplasmic overexpression of HPK1, MEKK1, and p-MKK4. The expression (%positive cells) of HPK1, MEKK1, and p-MKK4 in EMPD (92.3% ± 8.6%, 92.9% ± 8.6%, and 92.7% ± 7.4%, respectively) were significantly higher than in normal eccrine sweat gland cells (51.6% ± 10.4%, 44.7% ± 11.7%, 0% ± 0%). In addition, the expression of HPK1-, MEKK1-, and p-MKK4 in invasive EMPD was significantly higher than in noninvasive EMPD. Meanwhile, the expression of TAK1 was basically low and no significantly different between EMPD and normal controls. In conclusion, these results indicate that JNK pathway may play a role in the pathogenesis of EMPD.

Data collected from 12 stations in Daya Bay in different seasons in 2002 revealed the relation between water quality and phytoplankton response patterns. The results showed that Daya Bay could be divided into wet and dry seasons by multivariate statistical analysis. Principal component analysis indicated that temperature, chlorophyll a and nutrients were important components during the wet season (summer and autumn). The salinity and dissolved oxygen were the main environmental factors in the dry season (winter and spring). According to non-metric multidimensional scaling, there was a shift from the large diatoms in the dry season to the smaller line-chain taxa in the wet season with the condition of a high dissolved inorganic nitrogen and nitrogen to phosphorous concentration ratio. Nutrient changes can thus alter the phytoplankton community composition and biomass, especially near the aquaculture farm areas. There was no evidence of an effect of thermal water from the nearby nuclear power plants on the observed changes in phytoplankton community and biomass in 2002.

The objective is to identify the spatial and temporal variability of the hydrochemical quality of the water column in a subtropical coastal system, Daya Bay, China. Water samples were collected in four seasons at 12 monitoring sites. The Southeast Asian monsoons, northeasterly from October to the next April and southwesterly from May to September have also an important influence on water quality in Daya Bay. In the spatial pattern, two groups have been identified, with the help of multidimensional scaling analysis and cluster analysis. Cluster I consisted of the sites S3, S8, S10 and S11 in the west and north coastal parts of Daya Bay. Cluster I is mainly related to anthropogenic activities such as fish-farming. Cluster II consisted of the rest of the stations in the center, east and south parts of Daya Bay. Cluster II is mainly related to seawater exchange from South China Sea.

Acid washing is a common method for soil remediation, but is not always efficient for chromium-contaminated soil. Both soil particle size and the forms of chromium existing in the soil affect the efficiency of soil washing. Laboratory batch and column dissolution experiments were conducted to determine the efficiencies of citric and hydrochloric acids as agents to extract chromium from soils contaminated with chromium. The effects of soil particle size and chromium fractionation on Cr leaching were also investigated. About 90% of chromium in the studied soil existed either in residual form or bound to iron and manganese oxides, and Cr fraction distributions were similar for all soil particle sizes. Almost all exchangeable and carbonate-bound chromium was removed by washing once with 0.5 M HCl, whereas organic chromium was more effectively removed by washing with citric acid rather than with HCl solution of the same concentration. For chromium fractions that were either bound to Fe-Mn oxides or existed as residual forms, the efficiencies of acid washing were usually 20% or less, except for 0.5 M HCl solution, which had much higher efficiencies. Separation of the soil sample by particle size before the separate washing of the soil fractions had little improvement on the chromium removal.

Background: The distinction between dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) is a well-known challenge for dermatopathologists. Immunohistochemical stains have been used to augment routine histological examination to aid in differentiating DF from DFSP. Collagen triple helix repeat containing-1 (Cthrc1) was identified as a novel gene expressed in the adventitia and neointima on arterial injury. It is indicated to be a cell type-specific inhibitor of transforming growth factor-β, which in turn impacts collagen type I and III deposition, neointimal formation, and dedifferentiation of stem cells. Cthrc1 has also been shown to be highly active and potent in degrading extracellular matrix proteins and was found to be overexpressed in several malignant tumours, such as breast cancer and malignant melanoma. To our knowledge, however, expression of Cthrc1 in DFSP and DF has not been studied before., Objectives: To assess the expression of Cthrc1 in DFSP and DF and to ascertain whether Cthrc1 is superior to antibodies traditionally used in differentiating DF from DFSP., Methods: Immunohistochemical staining was performed on 23 cases of DFSP and 35 cases of DF, using antibodies to Cthrc1, CD34, factor XIIIa, CD10 and stromelysin-3 (ST3)., Results: Twenty-two of 23 (96%) DFSP samples were positive for Cthrc1, whereas 32 of 35 (91%) DF samples were negative. CD34 was expressed in most DFSPs (22 of 23, 96%), whereas it was completely negative in most cases of DF (29 of 35, 83%). Expression of factor XIIIa was found in most cases of DF (33 of 35, 94%), whereas it was completely absent in 21 of 23 (91%) DFSP cases. Expression of CD10 was found in most cases of DF (30 of 35, 86%), whereas it was completely absent in 13 of 23 (57%) DFSP cases. ST3 was expressed strongly in most cases of DF (32 of 35, 91%), whereas it was completely absent in 18 of 23 (78%) DFSP cases. The preferential Cthrc1 staining of DFSP in comparison with DF was statistically significant (P < 0·01)., Conclusions: We confirmed that Cthrc1 is a positive marker for DFSP and that Cthrc1 staining might be more reliable than markers traditionally used. Cthrc1 was not positive in absolutely [corrected] all cases of DFSP, and combination with CD34, factor XIIIa and ST3 immunostaining could make the distinction more reliable., (© 2010 The Authors. BJD © 2010 British Association of Dermatologists 2010.)

Oxygen consumption and ammonia excretion of black carp (Mylopharyngdon piceus Richardson) (4.6±0.3 g) and allogynogenetic crucian carp (Carassius auratus gibelio ♀×Cyprinus carpio ♂) (5.7±0.5 g) were examined when fish fed two types of carbohydrate (dextrin and glucose) at two levels (20 and 40%) each. The diets were isonitrogenous (40% dry matter) and isocaloric at 18.5 kJ g(−1) (dry matter) by adjusting the oil content to 10.1 and 1.5%, respectively. In black carp, the interactions between the carbohydrate type and level were found in oxygen consumption at 3 and 6 h and in ammonia excretion at 6 h after feeding. At 20% carbohydrate, no significant difference was observed between dextrin and glucose in oxygen consumption. However, at 40% carbohydrate, oxygen consumption in fish fed glucose was significantly higher than that in fish fed dextrin at 3 and 6 h after feeding. Within the dextrin diets, no significant differences in both oxygen consumption and ammonia excretion were detected between the two carbohydrate levels. Within the glucose diets, however, fish fed 40% glucose showed significantly higher oxygen consumption than those fed 20% glucose at 3 and 6 h after feeding. Ammonia excretion in black carp fed 40% glucose was higher than that in black carp fed 40% dextrin at 6 h and also found higher than those in the other three treatments at 24 h after feeding. The postprandial oxygen consumption and the ammonia excretion in crucian carp fed 40% glucose were the highest, but no significant differences were observed. Our data indicate that the escalation of glucose to 40% in a fish diet results in high oxygen consumption and ammonia excretion in black carp, suggesting that the efficiency of glucose as an energy source for this fish is compromised by the high metabolic expenditure after feeding. Crucian carp, on the other hand, have a better ability to cope with dietary carbohydrates.