Univariable and multivariable mendelian randomization study revealed the modifiable risk factors of urolithiasis.

BACKGROUND: Urolithiasis is a common urological disease with increasing incidence worldwide, and preventing its risk poses significant challenges. Here, we used Mendelian randomization (MR) framework to genetically assess the causal nature of multifaceted risk factors on urolithiasis. METHODS: 17 potential risk factors associated with urolithiasis were collected from recently published observational studies, which can be categorized basically into lifestyle factors and circulating biomarkers. The instrumental variables of risk factors were selected from large-scale genome-wide association studies (N ≤ 607,291). Summary-level data on urolithiasis were obtained from UK Biobank (UKB) (3,625 cases and 459,308 noncases) and the FinnGen consortium (5,347 cases and 213,445 noncases). The univariable and multivariable MR analyses were applied to evaluate the causal, independent effect of these potential risk factors upon urolithiasis. Effects from the two consortia were combined by the meta-analysis methods. RESULTS: Higher genetically predicted sex hormone-binding globulin (SHBG, OR, 0.708; 95% CI, 0.555 to 0.903), estradiol (OR, 0.179; 95% CI, 0.042 to 0.751), tea intake (OR, 0.550; 95% CI, 0.345 to 0.878), alcoholic drinks per week (OR, 0.992; 95% CI, 0.987 to 0.997), and some physical activity (e.g., swimming, cycling, keeping fit, and bowling, OR, 0.054; 95% CI, 0.008 to 0.363) were significantly associated with a lower risk of urolithiasis. In the Multivariate Mendelian Randomization (MVMR) analyses, the significant causal associations between estradiol, SHBG, tea intake, and alcoholic drinks per week with urolithiasis were robust even after adjusting for potential confounding variables. However, the previously observed causal association between other exercises and urolithiasis was no longer significant after adjusting for these factors. CONCLUSIONS: The univariable and multivariable MR findings highlight the independent and significant roles of estradiol, SHBG, tea intake, and alcoholic drinks per week in the development of urolithiasis, which might provide a deeper insight into urolithiasis risk factors and supply potential preventative strategies.

Improved Performance for the Electrochemical Sensing of Acyclovir by Using the rGO-TiO2-Au Nanocomposite-Modified Electrode.

An electrochemical sensor for sensitive sensing of acyclovir (ACV) was designed by using the reduced graphene oxide-TiO2-Au nanocomposite-modified glassy carbon electrode (rGO-TiO2-Au/GCE). Transmission electron microscopy, X-ray diffractometer, and X-ray photoelectron spectroscopy were used to confirm morphology, structure, and composition properties of the rGO-TiO2-Au nanocomposites. Cyclic voltammetry and linear sweep voltammetry were used to demonstrate the analytical performance of the rGO-TiO2-Au/GCE for ACV. As a result, rGO-TiO2-Au/GCE exerted the best response for the oxidation of ACV under the pH of 6.0 PB solution, accumulation time of 80 s at open-circuit, and modifier amount of 7 µl. The oxidation peak currents of ACV increased linearly with its concentration in the range of 1-100 µM, and the detection limit was calculated to be 0.3 µM (S/N = 3). The determination of ACV concentrations in tablet samples also demonstrated satisfactory results.

One-pot green preparation of deep-ultraviolet and dual-emission carbon nanodots for dual-channel ratiometric determination of polyphenol in tea sample.

A novel deep-ultraviolet and dual-emission carbon nanodots (DUCDs)-based dual-channel ratiometric probe was prepared by a one-pot environmental-friendly hydrothermal process using guanidine as the only starting material for sensing polyphenol in tea sample (TPPs). Under the exposure to TPPs, the DUCDs not only provided a characteristic colorimetric response to TPPs, but also displayed TPPs-sensitive ratiometric fluorescence quenching. The detection mechanism was proved to be that enrichment-specific hydroxyl sites (e.g., -NH2 and -COOH) of DUCDs can specifically react with phenolic hydroxyl groups of TPPs to generate dynamic amide and carboxylate bonds by dehydration and/or condensation reaction. As a result, a new carbon nanomaterial with decrement of surface passivation groups, inherent light-absorbing, and invalid fluorescence emission was generated. The ratio (FL297nm/FL395nm) of fluorescence intensity at 297 nm and 395 nm of DUCDs excited at 275 nm decreased with increasing TPPs concentration. The linearity range was 5.0 ng/mL to 100 µg/mL with a detection limit (DL) of 3.5 ± 0.04 ng/mL for TPPs (n = 3, 3σ/k). Colorimetry of DUCDs, best measured as absorbance at 320 nm, was increased linearly in the TPP concentration range 200 ng/mL-200 µg/mL with a DL of 94.7 ± 0.04 ng/mL (n = 3, 3σ/k). The probe was successfully applied to the determination of TPPs in real tea samples, showing potential application prospects in food analysis.

UV-assisted one-pot synthesis of bimetallic Ag-Pt decorated reduced graphene oxide for colorimetric determination of hydrogen peroxide.

Bimetallic Ag-Pt nanoparticles decorated on the surface of reduced graphene oxide (Ag-Pt/rGO) were designed and selected as a nanozyme for the assay of hydrogen peroxide. The nanocomposites were prepared through a one-pot reduction of potassium chloroplatinate, silver nitrate, and graphene oxide under ultraviolet irradiation without using any extra chemical reducing agents or surfactants. The successful formation of Ag-Pt/rGO nanocomposites was confirmed by transmission electron microscopy, energy disperse spectroscopy mapping, X-ray photoelectron spectroscopy, and X-ray diffraction analysis. Significantly, Ag-Pt/rGO nanocomposites possessed excellent peroxidase-like activity toward the catalytic oxidation of 3,3',5,5'-tetramethylbenzidine to form a blue product in the presence of hydrogen peroxide. Steady-state kinetics studies suggested that Ag-Pt/rGO nanocomposites had high affinity to hydrogen peroxide. Based on these properties, a convenient and sensitive method for the colorimetric determination of hydrogen peroxide was developed. Under optimal conditions, the absorbance at 652 nm increases linearly in the 10-100 µM and 100 µM-1 mM ranges of hydrogen peroxide concentration, and the detection limit is 0.9 µM (S/N = 3). The method was successfully applied to the determination of hydrogen peroxide in real water samples. Graphical abstract Ag-Pt/rGO nanocomposites were prepared by a one-pot UV irradiation method and used as a novel nanozyme for colorimetric determination of H2O2.

Developmental Expression of SULT1C4 Transcript Variants in Human Liver: Implications for Discordance Between SULT1C4 mRNA and Protein Levels.

The cytosolic sulfotransferases (SULTs) metabolize a variety of xenobiotic and endogenous substrates. Several SULTs are expressed in the fetus, implying that these enzymes have important functions during human development. We recently reported that while SULT1C4 mRNA is abundant in prenatal human liver specimens, SULT1C4 protein is barely detectable. Two coding transcript variants (TVs) of SULT1C4 are indexed in GenBank, TV1 (full-length) and TV2 (lacking exons 3 and 4). The purpose of this study was to evaluate expression of the individual TVs as a clue for understanding the discordance between mRNA and protein levels. Reverse-transcription polymerase chain reaction was initially performed to identify TVs expressed in intestinal and hepatic cell lines. This analysis generated fragments corresponding to TV1, TV2, and a third variant that lacked exon 3 (E3DEL). Using reverse-transcription quantitative polymerase chain reaction assays designed to quantify TV1, TV2, or E3DEL individually, all three TVs were more highly expressed in prenatal than postnatal specimens. TV2 levels were ∼fivefold greater than TV1, while E3DEL levels were minimal. RNA sequencing (RNA-seq) analysis of another set of liver specimens confirmed that TV1 and TV2 levels were highest in prenatal liver, with TV2 higher than TV1. RNA-seq also detected a noncoding RNA, which was also more abundant in prenatal liver. Transfection of HEK293T cells with plasmids expressing individual Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys-tagged SULT1C4 isoforms demonstrated that TV1 produced much more protein than did TV2. These data suggest that the lack of correspondence between SULT1C4 mRNA and protein levels in human liver is likely attributable to the inability of the more abundant TV2 to produce stable protein. SIGNIFICANCE STATEMENT: Cytosolic sulfotransferases (SULTs) metabolize a variety of xenobiotic and endogenous substrates, and several SULTs are highly expressed in the fetus, implying that they have important functions during human development. SULT1C4 is highly expressed in prenatal liver at the mRNA level but not the protein level. This study provides an explanation for this discordance by demonstrating that the predominant SULT1C4 transcript is a variant that produces relatively little protein.

Au-Hg/rGO with enhanced peroxidase-like activity for sensitive colorimetric determination of H2O2.

The Au-Hg amalgam anchored on the surface of reduced graphene oxide nanosheets (Au-Hg/rGO) has been synthesized successfully and characterized by various techniques such as transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The Au-Hg/rGO nanocomposites were found to possess excellent peroxidase-like catalytic activity and can quickly catalyze the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxTMB in the presence of H2O2. The obvious color change offered accurate determination of the H2O2 concentration by recording the absorbance at 652 nm using a UV-vis spectrophotometer. The linear response range for H2O2 was from 5 µM to 100 µM and the detection limit was 3.25 µM (S/N = 3). Furthermore, a kinetic study indicated that the catalytic behavior of Au-Hg/rGO nanocomposites followed the typical Michaelis-Menten theory and Au-Hg/rGO nanocomposites showed good affinity for H2O2. We envision that the simple and sensitive colorimetric detection system holds great promising applications in clinical diagnostics and food and environment monitoring.

A voltammetric sensor based on reduced graphene oxide-hemin-Ag nanocomposites for sensitive determination of tyrosine.

A novel voltammetric sensor was designed and used for the determination of l-tyrosine (l-Tyr) by surface modification of a glassy carbon electrode with reduced graphene oxide-hemin-Ag (rGO-H-Ag) nanocomposites. The nanocomposites were synthesized by a facile one-pot hydrothermal method and characterized by means of transmission electron microscopy and Raman spectroscopy. The determination of l-Tyr was investigated by cyclic voltammetry and further quantified using differential pulse voltammetry. The results revealed a significant enhanced electrochemical oxidation effect for l-Tyr at the nanocomposites modified electrode. Two linear ranges from 0.1 to 100 µM and 100 to 1000 µM as well as a low detection limit of 30 nM (S/N = 3) were obtained. In addition, the sensor also demonstrated good selectivity, reproducibility and stability.

Aggregation-Induced Emission Behavior of Dual-NIR-Emissive Zinc-Doped Carbon Nanosheets for Ratiometric Anthrax Biomarker Detection.

The development of near-infrared (NIR) emission nanoprobes for the ratiometric fluorescent determination of living cells in vitro/vivo is of great analytical importance. In this work, dual-NIR-emissive Zn-doped carbon-based nanosheets (Zn-CNSHs) were prepared with a beneficial and special donor-π-acceptor-conjugated (D-π-A-conjugated) spatial framework, which resulted in not only a much lower HOMO-LUMO energy level but also excellent biocompatibility and physicochemical properties. The Zn-CNSHs were prepared by simple one-pot solvothermal synthesis with zinc gluconate (ZGN) and a strong acid and exhibited two distinctive photoluminescence (PL) peaks at 620 and 720 nm with the 600 nm excitation. The 620 nm peak intensity was dependent on dipicolinic acid (DPA) owing to the aggregation-induced emission enhancement effect via the strong intersheet hydrogen bonds between Zn-CNSHs and DPA, enabling the ratiometric fluorescent determination of DPA, an important clinical anthrax biomarker. An excellent calibration curve showed linear regions over the range of 0.05-500 µM between the ratio of PL intensity (PL620 nm/PL720 nm) and the concentrations of DPA. The detection limit was down to 21.7 nM. Based on the high stability, low cytotoxicity, high selectivity, and outstanding PL-reliant sensitivity for the DPA assay, the nanoprobe has been successfully used to monitor DPA in serum, wastewater, and cells.

Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development.

Cytosolic sulfotransferases (SULTs) are expressed during early life and therefore metabolize endogenous and xenobiotic chemicals during development. Little is currently known about the regulation of individual SULTs in the developing human liver. We characterized SULT expression in primary cultures of human fetal hepatocytes and the HepaRG model of liver cell differentiation. SULT1A1 (transcript variants 1-4), SULT1C2, SULT1C4, SULT1E1, and SULT2A1 were the most abundant transcripts in human fetal hepatocytes. In HepaRG cells, SULT1B1, SULT1C2/3/4, and SULT1E1 mRNA levels increased during the transition from proliferation to confluency and then decreased as the cells underwent further differentiation. By contrast, SULT2A1 mRNA levels increased during differentiation, whereas SULT1A1 and SULT2B1 mRNA levels remained relatively constant. The temporal patterns of SULT1C2, SULT1E1, and SULT2A1 protein content were consistent with those observed at the mRNA level. To identify regulators of SULT expression, cultured fetal hepatocytes and HepaRG cells were treated with a panel of lipid- and xenobiotic-sensing receptor activators. The following effects were observed in both fetal hepatocytes and HepaRG cells: 1) liver X receptor activator treatment increased SULT1A1 transcript variant 5 levels; 2) vitamin D receptor activator treatment increased SULT1C2 and SULT2B1 mRNA levels; and 3) farnesoid X receptor activator treatment decreased SULT2A1 expression. Activators of aryl hydrocarbon receptor, constitutive androstane receptor, pregnane X receptor, and peroxisome proliferator-activated receptors produced additional gene-dependent effects on SULT expression in HepaRG cells. These findings suggest that SULT-regulating chemicals have the potential to modulate physiologic processes and susceptibility to xenobiotic stressors in the developing human liver.

Transcriptional Regulation of Human Cytosolic Sulfotransferase 1C3 by Peroxisome Proliferator-Activated Receptor γ in LS180 Human Colorectal Adenocarcinoma Cells.

Cytosolic sulfotransferase 1C3 (SULT1C3) is the least characterized of the three human SULT1C subfamily members. Originally identified as an orphan SULT by computational analysis of the human genome, we recently reported that SULT1C3 is expressed in human intestine and LS180 colorectal adenocarcinoma cells and is upregulated by agonists of peroxisome proliferator-activated receptor (PPAR) α and γ To determine the mechanism responsible for PPAR-mediated upregulation, we prepared reporter plasmids containing fragments of the SULT1C3 5'-flanking region. During initial attempts to amplify a 2.8-kb fragment from different sources of human genomic DNA, a 1.9-kb fragment was sometimes coamplified with the expected 2.8-kb fragment. Comparison of the 1.9-kb fragment sequence to the published SULT1C3 5'-flanking sequence revealed an 863-nt deletion (nt -146 to -1008 relative to the transcription start site). Transfection analysis in LS180 cells demonstrated that PPARα, δ, and γ agonist treatments induced luciferase expression from a reporter plasmid containing the 2.8-kb but not the 1.9-kb fragment. The PPAR agonists also activated a 1-kb reporter containing the 863-nt deletion region. Computational analysis identified three peroxisome proliferator response elements (PPREs) within the 863-nt region and serial deletions and site-directed mutations indicated that the most distal PPRE (at nt -769) was essential for obtaining PPAR-mediated transcriptional activation. Although agonists of all three PPARs could activate SULT1C3 transcription, RNA interference analysis indicated the predominance of PPARγ These data demonstrate that the PPARγ regulatory network includes SULT1C3 and imply that this enzyme contributes to the control of such PPARγ-regulated intestinal processes as growth, differentiation, and metabolism.

A label-free photoelectrochemical aptasensor for bisphenol A based on surface plasmon resonance of gold nanoparticle-sensitized ZnO nanopencils.

A simple and novel photoelectrochemical (PEC) aptasensor for selective detection of bisphenol A (BPA) was developed using surface plasmon resonance of Au nanoparticles activated ZnO nanopencils. With the irradiation of simulated light, the increased photocurrent of nano-Au/ZnO than that of pure ZnO nanopencil is induced by the hot electrons from excited Au nanoparticles. The perfect selectivity is attributed to the specific binding of BPA to its aptamer. With the addition of BPA, the conformation of aptamer changed to a G-quadruplex structure, which resulted in the blockages of photogenerated electron-transfer channels. Based on the above mechanisms and the optimized conditions, the assembled PEC aptasensor was linear with the concentration of BPA in the range of 1-1000nmolL(-1) with a detection limit of 0.5nmolL(-1). The presence of the same concentration and similar structure of other organics did not interfere in the detection of BPA and the recovery was between 96.2% and 108.4%. It has been successfully applied to the detection of BPA in drinking water and liquid milk samples. This PEC aptasensor has good performances in novelty, selectivity, sensitivity and low cost, and it provides an alternative approach to the detection of BPA.

Transcriptional Regulation of Cytosolic Sulfotransferase 1C2 by Vitamin D Receptor in LS180 Human Colorectal Adenocarcinoma Cells.

The factors that regulate expression of genes in the 1C family of human cytosolic sulfotransferases (SULT1C) are not well understood. In a recent study evaluating the effects of a panel of transcription factor activators on SULT1C family member expression in LS180 human colorectal adenocarcinoma cells, we found that SULT1C2 expression was significantly increased by 1α,25-dihydroxyvitamin D3 (VitD3) treatment. The objective of our current study was to identify the mechanism responsible for VitD3-mediated activation of SULT1C2 transcription. VitD3 treatment of LS180 cells activated transcription of a transfected luciferase reporter plasmid that contained ∼5 kilobase pairs (kbp) of the SULT1C2 gene, which included 402 nucleotides (nt) of the noncoding exon 1, all of intron 1, and 21 nt of exon 2. Although computational analysis of the VitD3-responsive region of the SULT1C2 gene identified a pregnane X receptor (PXR)-binding site within exon 1, the transfected 5 kbp SULT1C2 reporter was not activated by treatment with rifampicin, a prototypical PXR agonist. However, deletion or mutation of the predicted PXR-binding site abolished VitD3-mediated SULT1C2 transcriptional activation, identifying the site as a functional vitamin D response element (VDRE). We further demonstrated that vitamin D receptor (VDR) can interact directly with the SULT1C2 VDRE sequence using an enzyme-linked immunosorbent assay-based transcription factor binding assay. In conclusion, VitD3-inducible SULT1C2 transcription is mediated through a VDRE in exon 1. These results suggest a role for SULT1C2 in VitD3-regulated physiologic processes in human intestine.

A sensitive and label-free photoelectrochemical aptasensor using Co-doped ZnO diluted magnetic semiconductor nanoparticles.

Co-doped ZnO diluted magnetic semiconductor as a novel photoelectric beacon was first constructed for photoelectrochemical (PEC) aptasensor of acetamiprid. The fabricated PEC sensing is based on the specific binding of acetamiprid and its aptamer, which induces the decreasement of enhanced photocurrent produced by the electron donor of quercetin. Co(2+) doping has a beneficial effect in extending the band width of light absorption of ZnO into the visible region and to promote the separation of the photoinduced carriers due to the sp-d exchange interactions existing between the band electrons and the localized d electrons of Co(2+). The fabricated aptasensor was linear with the concentration of acetamiprid in the range of 0.5-800 nmolL(-1) with the detection limit of 0.18 nmolL(-1). The presence of same concentration of other conventional pesticides did not interfere in the detection of acetamiprid and the recovery is between 96.2% and 103.7%. This novel PEC aptasensor has good performances with high sensitivity, good selectivity, low cost and portable features. The strategy of Co-doped ZnO diluted magnetic semiconductor paves a new way to improve the performances of PEC aptasensor.

Reduced graphene oxide-Hemin-Au nanohybrids: Facile one-pot synthesis and enhanced electrocatalytic activity towards the reduction of hydrogen peroxide.

A facile and effective strategy is demonstrated for the synthesis of ternary reduced graphene oxide-Hemin-Au (rGO-H-Au) nanohybrids. The nanohybrids were synthesized through a one-pot in situ reduction of GO and HAuCl4 under alkaline conditions using GO, Hemin and HAuCl4 as the starting materials. The synthesis process can be finished within 1h in a solution phase, without adding any additional surfactant, stabilizing agent and toxic or harsh chemical reducing agents. The resulting nanohybrids were characterized by UV-vis spectroscopy, Raman spectroscopy, transmission electron microscopy (TEM), and so on. Electrochemical measurements showed that the rGO-H-Au nanohybrids exhibited good electrocatalytic activity for the reduction of hydrogen peroxide (H2O2). Based on this property, a simple and highly sensitive amperometric biosensor for H2O2 had been developed. The linear relationships were obtained from 0.1 µM to 40 µM and the detection limit was estimated to be 30 nM. The simple and sensitive sensing platform showed great promising applications in the pharmaceutical, clinical and industrial detection of H2O2.

Direct electrolytic exfoliation of graphite with hemin and single-walled carbon nanotube: Creating functional hybrid nanomaterial for hydrogen peroxide detection.

We present a new, facile and efficient method to prepare functional graphene (GN) hybrid nanomaterials using direct electrolytic exfoliation of graphite robs in hemin (HN) and single-walled carbon nanotube (SWCNT) solution. During the exfoliation process, HN and SWCNT were simultaneously adsorbed on the surface of GN nanosheets through noncovalent π-π interaction, and then 3D GN-HN-SWCNT hybrid nanomaterials were formed. Due to the synergic effect among GN, HN, and SWCNT, these hybrid nanomaterials possessed excellent electrocatalysis properties and were used to construct novel electrochemical biosensor for H2O2 determination. The results displayed a wide linear range of 0.2 µM-0.4 mM and a low detection limit of 0.05 µM. Moreover, the developed sensor was successfully applied for real samples, such as beverages, and showed great promise in routine sensing applications.

Upregulation of UGT2B4 Expression by 3'-Phosphoadenosine-5'-Phosphosulfate Synthase Knockdown: Implications for Coordinated Control of Bile Acid Conjugation.

During cholestasis, the bile acid-conjugating enzymes, SULT2A1 and UGT2B4, work in concert to prevent the accumulation of toxic bile acids. To understand the impact of sulfotransferase deficiency on human hepatic gene expression, we knocked down 3'-phosphoadenosine-5'-phosphosulfate synthases (PAPSS) 1 and 2, which catalyze synthesis of the obligate sulfotransferase cofactor, in HepG2 cells. PAPSS knockdown caused no change in SULT2A1 expression; however, UGT2B4 expression increased markedly (∼41-fold increase in UGT2B4 mRNA content). Knockdown of SULT2A1 in HepG2 cells also increased UGT2B4 expression. To investigate the underlying mechanism, we transfected PAPSS-deficient HepG2 cells with a luciferase reporter plasmid containing ∼2 Kb of the UGT2B4 5'-flanking region, which included a response element for the bile acid-sensing nuclear receptor, farnesoid X receptor (FXR). FXR activation or overexpression increased UGT2B4 promoter activity; however, knocking down FXR or mutating or deleting the FXR response element did not significantly decrease UGT2B4 promoter activity. Further evaluation of the UGT2B4 5'-flanking region indicated the presence of distal regulatory elements between nucleotides -10090 and -10037 that negatively and positively regulated UGT2B4 transcription. Pulse-chase analysis showed that increased UGT2B4 expression in PAPSS-deficient cells was attributable to both increased mRNA synthesis and stability. Transfection analysis demonstrated that the UGT2B4 3'-untranslated region decreased luciferase reporter expression less in PAPSS-deficient cells than in control cells. These data indicate that knocking down PAPSS increases UGT2B4 transcription and mRNA stability as a compensatory response to the loss of SULT2A1 activity, presumably to maintain bile acid-conjugating activity.

Regulation of human cytosolic sulfotransferases 1C2 and 1C3 by nuclear signaling pathways in LS180 colorectal adenocarcinoma cells.

Cytosolic sulfotransferases (SULTs) catalyze the sulfate conjugation of a myriad of endogenous and xenobiotic substrates. Among the 13 human SULTs, little is known regarding regulation of the SULT1C subfamily. We evaluated the effects of a panel of transcription factor activators on levels of SULT1C mRNA (1C2 and 1C3) and protein (1C2) in LS180 colorectal adenocarcinoma cells. Treatment with 3-[3-[N-(2-chloro-3-trifluoromethylbenzyl)-(2,2-diphenylethyl)amino]propyloxy]phenylacetic acid hydrochloride [GW3965, liver X receptor (LXR) activator], 3-(2,6-dichlorophenyl)-4-(3'-carboxy-2-chlorostilben-4-yl)oxymethyl-5-isopropylisoxazole [GW4064, farnesoid X receptor (FXR)], or rifampicin [pregnane X receptor (PXR)] moderately (≤2-fold) increased both SULT1C2 and SULT1C3 mRNA levels. 1α,25-Dihydroxyvitamin D3 [1,25(OH)2D3, vitamin D receptor (VDR)] selectively upregulated SULT1C2, whereas ciprofibrate [peroxisome proliferator-activated receptor α (PPARα)], rosiglitazone (PPARγ), and 2,3,7,8-tetrachlorodibenzo-p-dioxin [aryl hydrocarbon receptor (AhR)] selectively increased SULT1C3 mRNA levels. SULT1C2 protein content was strongly increased by 1,25(OH)2D3 treatment and moderately increased by GW3965, GW4064, and rifampicin. To evaluate SULT1C2 transcriptional regulation, treatment effects were determined on reporter activity from transfected constructs containing ∼10 kb of the SULT1C2 gene. Treatment with GW3965, GW4064, or 1,25(OH)2D3 increased reporter activity ∼2-, 5-, and 5.5-fold, respectively, from a construct containing mostly intron 1 of the SULT1C2 gene. Expression of AhR, LXRα, LXRß, PPARα, PPARγ, PXR, and VDR was confirmed in LS180 cells using quantitative reverse-transcription polymerase chain reaction; however, FXR expression was negligible, suggesting that GW4064 increased SULT1C expression through an FXR-independent mechanism. Collectively, our findings are the first to characterize the regulation of human SULT1C2 and SULT1C3 expression by several transcription factor activators. Further, we determined that responsive regions for LXR and VDR are likely contained within intron 1 of the SULT1C2 gene.

[Open reduction and mini-plate internal fixation for the treatment of fracture and dislocation of coccyx].

OBJECTIVE: To explore the therapeutic methods of fracture and dislocation of coccyx and evaluate its curative effects. METHODS: From May 2002 to March 2010,56 patients with fracture and dislocation of coccyx were divided into surgical treatment group and non-surgical treatment group. There were 7 males and 20 females in surgical treatment group with an average age of (48.1 +/- 0.6) years (ranged, 29 to 62 years), treated with open reduction and mini-plate internal fixation. There were 8 males and 21 females in non-surgical treatment group with an average age of (47.5 +/- 0.9) years (ranged, 19 to 54 years),treated with manipulative reduction. All patients were underwent X-ray examination and were finally diagnosed before treatment. Clinical symptoms and Visual Analogue Scales (VAS) of all patients were statistically analyzed before and after treatment. RESULTS: There was no significant difference between two groups in gender, age, BMI index and VAS evaluation. All patients were followed up from 12 to 25 months with an average of 17.2 months. In surgical treatment group,there were 26 cases with I/a incision and 1 case with II/a incision; the excellent rate of clinical symptom was respectively 92.6% and 100% at leaving hospital and final follow-up; the improvement rate of VAS was 97.6% and was excellent result;internal fixtures were removed at the 1 to 2 years after treatment and no unwell symptoms occurred; VAS of all patients in the group was 0 point. In non-surgical treatment group,the excellent rate of clinical symptom was respectively 72.4% and 82.8% at leaving hospital and final follow-up; the improvement rate of VAS was 72.1% and was good result. There was significant difference in clinical results between two groups (P<0.05). CONCLUSION: The results indicated that fracture and dislocation of coccyx should be treated in time. For the treatment of patients with manipulative reduction failures, instability reduction by X-ray examination and serious rectal irritation, open reduction and mini-plate internal fixation can obtain satisfactory results.

Event-related synchronization of delta and beta oscillations reflects developmental changes in the processing of affective pictures during adolescence.

Recent research has determined that affective pictures modulate event-related delta and beta oscillations in adults. However, it is unclear whether these brain oscillations reflect developmental changes in the processing of affective information during adolescence. EEG data were collected from 51 adolescents and 18 undergraduates as they viewed a total of 90 pictures. In the range of fast wave activities, event-related synchronization (ERS) in the beta band varied with emotional valence, indicating that beta ERS is indicative of early bottom-up processing of visual emotional stimuli. Adolescents at the age of 12years exhibited more positive beta ERS amplitudes over posterior brain regions for positive versus neutral pictures compared to adolescents at the ages 14years, 16years and in young adults; however, no age-related differences were found for negative versus neutral pictures. In the range of slow wave activities, delta ERSs and late positive potential (LPP) amplitudes exhibited affective modulation and decreased over anterior brain regions from between the age of 12years and early adulthood. These slow wave activities (delta and LPPs) reflected top-down attention to the motivational relevance of the emotional stimuli. Taken together, these observations suggest that adolescents exhibit dissociable ERS patterns in the delta and beta bands during affective processing. Furthermore, adolescents undergo age-dependent changes in oscillatory brain reorganization. Our results should be useful to researchers interested in affective processing during adolescence.

Regulation of murine hepatic hydroxysteroid sulfotransferase expression in hyposulfatemic mice and in a cell model of 3'-phosphoadenosine-5'-phosphosulfate deficiency.

The cytosolic sulfotransferases (SULTs) catalyze the sulfate conjugation of nucleophilic substrates, and the cofactor for sulfonation, 3'-phosphoadenosine-5'-phosphosulfate (PAPS), is biosynthesized from sulfate and ATP. The phenotype of male knockout mice for the NaS1 sodium sulfate cotransporter includes hyposulfatemia and increased hepatic expression of mouse cytoplasmic sulfotransferase Sult2a and Sult3a1. Here we report that in 8-week-old female NaS1-null mice, hepatic Sult2a1 mRNA levels were ∼51-fold higher than they were in a wild-type liver but expression of no other Sult was affected. To address whether hyposulfatemia-inducible Sult2a1 expression might be due to reduced PAPS levels, we stably knocked down PAPS synthases 1 and 2 in HepG2 cells (shPAPSS1/2 cells). When a reporter plasmid containing at least 233 nucleotides (nt) of Sult2a1 5'-flanking sequence was transfected into shPAPSS1/2 cells, reporter activity was significantly increased relative to the activity that was seen for reporters containing 179 or fewer nucleotides. Mutation of an IR0 (inverted repeat of AGGTCA, with 0 intervening bases) nuclear receptor motif at nt -191 to 180 significantly attenuated the PAPSS1/2 knockdown-mediated increase. PAPSS1/2 knockdown significantly activated farnesoid X receptor (FXR), retinoid-related orphan receptor, and pregnane X receptor responsive reporters, and treatment with the FXR agonist GW4064 [3-(2,6-dichlorophenyl)-4-(3'-carboxy-2-chlorostilben-4-yl)oxymethyl-5-isopropylisoxazole] increased Sult2a1 promoter activity when the IR0 was intact. Transfection of shPAPSS1/2 cells with FXR small interfering RNA (siRNA) significantly reduced the Sult2a1 promoter activity. The impact of PAPSS1/2 knockdown on Sult2a1 promoter activity was recapitulated by knocking down endogenous SULT2A1 expression in HepG2 cells. We propose that hyposulfatemia leads to hepatic PAPS depletion, which causes loss of SULT2A1 activity and results in accumulation of nonsulfated bile acids and FXR activation.