Goos-Hänchen shift in cryogenic defect photonic crystals composed of superconductor HgBa2Ca2Cu3O8+δ.

We explore theoretically Goos-Hänchen (GH) shift around the defect mode in superconducting defective photonic crystals (PCs) in cryogenic environment. The defective PCs are constructed by alternating semiconductors and superconductors. A defect mode arises in the photonic bandgap and sensitively depends on environment temperature and hydrostatic pressure. Reflection and transmission coefficient phases make an abruptly jump at the defect mode and giant GH shifts have been achieved around this mode. The maximum GH shift can get as high as 103λ (incident wavelength), which could be modulated by the values of temperature and hydrostatic pressure. This study may be utilized for pressure- or temperature-sensors in cryogenic environment.

Adaptive responses of erythritol-producing Yarrowia lipolytica to thermal stress after evolution.

Elucidation of the thermotolerance mechanism of erythritol-producing Yarrowia lipolytica is of great significance to breed robust industrial strains and reduce cost. This study aimed to breed thermotolerant Y. lipolytica and investigate the mechanism underlying the thermotolerant phenotype. Yarrowia lipolytica HT34, Yarrowia lipolytica HT36, and Yarrowia lipolytica HT385 that were capable of growing at 34 °C, 36 °C, and 38.5 °C, respectively, were obtained within 150 days (352 generations) by adaptive laboratory evolution (ALE) integrated with 60Co-γ radiation and ultraviolet ray radiation. Comparative genomics analysis showed that genes involved in signal transduction, transcription, and translation regulation were mutated during adaptive evolution. Further, we demonstrated that thermal stress increased the expression of genes related to DNA replication and repair, ceramide and steroid synthesis, and the degradation of branched amino acid (BCAA) and free fatty acid (FFA), while inhibiting the expression of genes involved in glycolysis and the citrate cycle. Erythritol production in thermotolerant strains was remarkably inhibited, which might result from the differential expression of genes involved in erythritol metabolism. Exogenous addition of BCAA and soybean oil promoted the growth of HT385, highlighting the importance of BCAA and FFA in thermal stress response. Additionally, overexpression of 11 out of the 18 upregulated genes individually enabled Yarrowia lipolytica CA20 to grow at 34 °C, of which genes A000121, A003183, and A005690 had a better effect. Collectively, this study provides novel insights into the adaptation mechanism of Y. lipolytica to thermal stress, which will be conducive to the construction of thermotolerant erythritol-producing strains. KEY POINTS: • ALE combined with mutagenesis is efficient for breeding thermotolerant Y. lipolytica • Genes encoding global regulators are mutated during thermal adaptive evolution • Ceramide and BCAA are critical molecules for cells to tolerate thermal stress.

Inhibition of hyphal formation together with biochar addition promotes erythritol production by Yarrowia lipolytica.

This study aimed to investigate the effect of hyphal formation in Yarrowia lipolytica and biochar addition on erythritol production by submerged fermentation. Hyphal formation significantly inhibited erythritol production by Y. lipolytica. Transcriptome analysis suggested that the impaired erythritol synthesis of hyphal cells was associated with the differential expression of genes involved in amino acid metabolism, lipid metabolism, and cell wall stability. Deletion of RAS2 responsible for yeast-to-hypha transition and EYD1 included in erythritol degradation blocked hyphal formation and improved erythritol production. Biochar prepared from corncob, sugarcane bagasse (SB), corn straw, peanut shell, coconut shell, and walnut shell (WS) had a positive effect on erythritol production, of which WS pyrolyzed at 500°C (WSc) performed the best in flask fermentation. In a 3.7 L bioreactor, 220.20 ± 10 g/L erythritol with a productivity of 2.30 ± 0.10 g/L/h was obtained in the presence of 1.4% (w/v) WSc and 0.7% SBc (SB pyrolyzed at 500°C) within 96 h. These results suggest that inhibition of hyphal formation together with biochar addition is an efficient way to promote erythritol production.

Ultrasonic-assisted activated carbon separation removing bacterial endotoxin from salvia miltiorrhizae injection.

Ultrasonic-assisted activated carbon separation (UACS) was first employed to improve product quality by regulating adsorption rate and removing bacterial endotoxin from salvia miltiorrhizae injection. The adsorption rate was related to three variables: activated carbon dosage, ultrasonic power, and pH. With the increase of activated carbon dosage from 0.05 % to 1.0 %, the adsorption rates of salvianolic acids and bacterial endotoxin increased simultaneously. The adsorption rates at which bacteria endotoxins increased from 52.52 % to 97.16 % were much higher than salvianolic acids. As the ultrasonic power increased from 0 to 700 W, the adsorption rates of salvianolic acids on activated carbon declined to less than 10 %, but bacterial endotoxin increased to more than 87 %. As the pH increased from 2.00 to 8.00, the adsorption rate of salvianolic acid dropped whereas bacterial endotoxin remained relatively stable. On the basis of response surface methodology (RSM), the optimal separation conditions were established to be activated carbon dose of 0.70 %, ultrasonic power of 600 W, and pH of 7.90. The experimental adsorption rates of bacterial endotoxin were 94.15 %, which satisfied the salvia miltiorrhizae injection quality criterion. Meanwhile, salvianolic acids' adsorption rates were 1.92 % for tanshinol, 4.05 % for protocatechualdehyde, 2.21 % for rosmarinic acid, and 3.77 % for salvianolic acid B, all of which were much lower than conventional activated carbon adsorption (CACA). Salvianolic acids' adsorption mechanism on activated carbon is dependent on the component's molecular state. Under ideal separation conditions, the molecular states of the four salvianolic acids fall between 1.13 % and 6.60 %. The quality of salvia miltiorrhizae injection can be improved while maintaining injection safety by reducing the adsorption rates of salvianolic acids to less than 5 % by the use of ultrasound to accelerate the desorption mass transfer rate on the activated carbon surface. When activated carbon adsorption was used in the process of producing salvia miltiorrhizae injection, the pH of the solution was around 5.00, and the proportion of each component's molecular state was tanshinol 7.05 %, protocatechualdehyde 48.93 %, rosmarinic acid 13.79 %, and salvianolic acid B 10.28 %, respectively. The loss of useful components was evident, and the corresponding activated carbon adsorption rate ranged from 20.74 % to 41.05 %. The average variation rate in plasma His and IgE was significant (P < 0.05) following injection of 0.01 % activated carbon, however the average variation rate of salvia miltiorrhizae injection was dramatically decreased with the use of UACS and CACA (P > 0.05). The ultrasonic at a power intensity of 60 W/L and the power density of 1.20 W/cm2 may resolve the separation contradiction between salvianolic acids and bacterial endotoxin, according to experiments conducted with UACS at different power intensities. According to this study, UACS has a lot of potential applications in the pharmaceutical manufacturing industry and may represent a breakthrough in the field of ultrasonic separation.

Mechanism and evolutionary analysis of Yarrowia lipolytica CA20 capable of producing erythritol with a high yield based on comparative genomics.

Combined mutagenesis is widely applied for the breeding of robust Yarrowia lipolytica used in the production of erythritol. However, the changes of genome after mutagenesis remains unclear. This study aimed to unravel the mechanism involved in the improved erythritol synthesis of CA20 and the evolutionary relationship between different Y. lipolytica by comparative genomics analysis. The results showed that the genome size of Y. lipolytica CA20 was 20,420,510 bp, with a GC content of 48.97%. There were 6330 CDS and 649 ncRNA (non-coding RNA) in CA20 genome. Average nucleotide identity (ANI) analysis showed that CA20 genome possessed high similarity (ANI > 99.50%) with other Y. lipolytica strains, while phylogenetic analysis displayed that CA20 was classified together with Y. lipolytica IBT 446 and Y. lipolytica H222. CA20 shared 5342 core orthologous genes with the 8 strains while harbored 65 specific genes that mainly participated in the substrate and protein transport processes. CA20 contained 166 genes coding for carbohydrate-active enzymes (CAZymes), which was more than that found in other strains (108－137). Notably, 4, 2, and 13 different enzymes belonging to glycoside hydrolases (GHs), glycosyltransferases (GTs), and carbohydrate esterases (CEs), respectively, were only found in CA20. The enzymes involved in the metabolic pathway of erythritol were highly conserved in Y. lipolytica, except for transaldolase (TAL1). In addition, the titer and productivity of erythritol by CA20 were 190.97 g/L and 1.33 g/L/h, respectively, which were significantly higher than that of WT5 wherein 128.61 g/L and 0.92 g/L/h were obtained (P< 0.001). Five frameshift mutation genes and 15 genes harboring nonsynonymous mutation were found in CA20 compared with that of WT5. Most of these genes were involved in the cell division, cell wall synthesis, protein synthesis, and protein homeostasis maintenance. These findings suggested that the genome of Y. lipolytica is conserved during evolution, and the variance of living environment is one important factor leading to genome divergence. The varied number of CAZymes existed in Y. lipolytica is one factor that contributes to the performance difference. The increased synthesis of erythritol by Y. lipolytica CA20 is correlated with the improvement of the stability of cell structure and internal environment. The results of this study provide a basis for the directional breeding of robust strains used in erythritol production.

Recurrent spontaneous coronary artery dissection.

Spontaneous coronary artery dissection (SCAD) is a significant cause of myocardial infarction (MI) and is more prevalent in pregnancy. The disease is being increasingly appreciated and diagnosed with the development and application of coronary angiography and intravascular imaging. Recurrent spontaneous coronary artery dissection (R-SCAD) is relatively common, with recurrence rates ranging from 8 to 27%. R-SCAD usually involves anatomical sites different from the original SCAD lesion and can cause MI, ventricular arrhythmias, and cardiogenic shock. This study aims to conduct a comprehensive review of R-SCAD to identify early risk factors and guide prevention policies and interventions. In addition, the risk of R-SCAD in subsequent pregnancies in women with a history of SCAD is discussed.

Usage, Pleasure, Price, and Feeling: A Study on Shopping Orientation and Consumer Outcome.

Understanding the behavior of consumers and especially the purchase-related behavior has been a focus of research for the past decades. Thus, researchers and practitioners are curious to know how purchase patterns are different under different conditions such as product category, price, feeling, and so on. The primary focus of this study was to examine how the price of the products influences the purchase behavior of consumers across hedonic and utilitarian categories under regulatory focus theory (RFT). The secondary insight was to examine how mood can moderate this impact. We conducted three experimental studies to examine these research questions regarding the preference of consumers of hedonic (utilitarian) products when the price is low (high) and at different mood conditions in this purchase process. The results confirmed our hypothesis that product category has a significant impact on purchase choice of products and mood can mediate this impact. In the last section, we discussed the theoretical contribution, strategic insights for product designers and marketers, and possible future research directions.

Interaction with longan seed polyphenols affects the structure and digestion properties of maize starch.

This study investigated effects of longan seed polyphenols (LSPs) on the structure and digestion properties of starch, and discussed the interaction mechanism between starch and LSPs. The results showed cooking with 20 % LSPs did not change amylopectin chain length distribution of normal maize starch, however, the amylose content was reduced from 21.60 to 14.03 %. This suggests LSPs may interact with starch via non-covalent bond. Isothermal titration microcalorimetry and XRD results confirmed the existence of non-covalent interaction, and indicated that LSPs may enter the hydrophobic cavity of amylose, forming V-type inclusion complex. LSPs did not affect gelatinization temperatures of maize starch, whereas 20 % LSPs decreased the enthalpy change by about 26 %. The digestion results indicate significant inhibition effect of LSPs on the digestion of cooked starch, attributing to the interaction of LSPs with starch. These suggest potential applications of LSPs as functional ingredients in modulating postprandial glycemic response of starchy food.

Yin and Yang Regulation of Liver X Receptor α Signaling Control of Cholesterol Metabolism by Poly(ADP-ribose) polymerase 1.

Liver X receptor α (LXRα) controls a set of key genes involved in cholesterol metabolism. However, the molecular mechanism of this regulation remains unknown. The regulatory role of poly(ADP-ribose) polymerase 1 (PARP1) in cholesterol metabolism in the liver was examined. Activation of PARP1 in the liver suppressed LXRα sensing and prevented upregulation of genes involved in HCD-induced cholesterol disposal. Mechanistically, LXRα was poly(ADP-ribosyl)ated by activated PARP1, which decreased DNA binding capacity of LXRα, thus preventing its recruitment to the target promoter. Intriguingly, we found that unactivated PARP1 was indispensable for LXRα transactivation and target expression. Further exploration identified unactivated PARP1 as an essential component of the LXRα-promoter complex. Taken together, the results indicate that activated PARP1 suppresses LXRα activation through poly(ADP-ribosyl)ation, while unactivated PARP1 promotes LXRα activation through physical interaction. PARP1 is a pivotal regulator of LXRα signaling and cholesterol metabolism in the liver.

Downregulations of miR-449a and miR-145-5p Act as Prognostic Biomarkers for Endometrial Cancer.

This investigation aimed to explore the underlying prognosis-associated microRNA (miRNA) biomarkers in endometrial cancer. Homo sapiens miRNA data set GSE35794 and miRNA data in TGGA database were downloaded and applied to screen the differentially expressed miRNAs (DE-miRNAs) using unpaired t-test in limma package in R. Basing on Venn analysis, the overlapped DE-miRNAs were screened and their potential targets were predicted according to miRWalk followed by target functional enrichment analyses and protein-protein interaction network visualized using Cytoscape. Finally, according to the information provided by the The Cancer Genome Atlas (TCGA) database, correlations between miRNAs or targets and patient prognosis were analyzed by survival package in R. A total of 24 overlapped DE-miRNAs were identified between endometrioid endometrial cancer samples and normal samples. Then, the miRNA-target regulatory network was constructed, including 11 upregulated miRNAs (e.g., miR-200a, miR-200b, and miR-200c) and five downregulated miRNAs (e.g., miR-449a, miR-145-5p, and miR-145-3p). Lymphocyte enhancer factor-1 (LEF1) was predicted to be a target of miR-449a and SOX11 was a target of miR-145-5p. Functional enrichment analyses of these targets were significantly related to the biological process of "negative regulation of transcription from RNA polymerase II promoter" and "positive regulation of transcription from RNA polymerase II promoter" (e.g., NOTCH1, LEF1, and SOX11). In addition, survival analysis showed that miR-449a, miR-145-5p, and LEF1 were approximately correlated with the overall survival prognosis of endometrial cancer patients. Downregulations of miR-449a and miR-145-5p might be involved in the pathogenesis of endometrial cancer and could act as prognostic biomarkers for endometrial cancer patients.

Analysis of key genes and their functions in placental tissue of patients with gestational diabetes mellitus.

BACKGROUND: This study was aimed at screening out the potential key genes and pathways associated with gestational diabetes mellitus (GDM). METHODS: The GSE70493 dataset used for this study was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in the placental tissue of women with GDM in relation to the control tissue samples were identified and submitted to protein-protein interaction (PPI) network analysis and subnetwork module mining. Functional enrichment analyses of the PPI network and subnetworks were subsequently carried out. Finally, the integrated miRNA-transcription factor (TF)-DEG regulatory network was analyzed. RESULTS: In total, 238 DEGs were identified, of which 162 were upregulated and 76 were downregulated. Through PPI network construction, 108 nodes and 278 gene pairs were obtained, from which chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, protein tyrosine phosphatase, receptor type C (PTPRC), and human leukocyte antigen (HLA) were screened out as hub genes. Moreover, genes associated with the immune-related pathway and immune responses were found to be significantly enriched in the process of GDM. Finally, miRNAs and TFs that target the DEGs were predicted. CONCLUSIONS: Four candidate genes (viz., CXCL9, CXCL10, PTPRC, and HLA) are closely related to GDM. miR-223-3p, miR-520, and thioredoxin-binding protein may play important roles in the pathogenesis of this disease.

Serum miR-1181 and miR-4314 associated with ovarian cancer: MiRNA microarray data analysis for a pilot study.

OBJECTIVE: This study aims to identify serum microRNAs (miRNAs) related to ovarian cancer. STUDY DESIGN: MiRNA profiling data (GSE79943) were generated from the Gene Expression Omnibus, including 3 serum samples from healthy individuals and 4/3/16/6 serum samples from patients with ovarian cancer stage I/II/III/IV. Differentially expressed miRNAs (DEmiRNAs) were identified between controls and ovarian cancer stage I/II/III/IV by using limma package (p-value <0.05 and |log2 fold change| ≥0.5). miRWALK2.0 database was used to find experiment-validated targets of DEmiRNAs, and CTD database was utilized to screen known genes related to ovarian cancer. clusterProfiler package was used to perform pathway enrichment analysis of DEmiRNAs. Targets of DEmiRNAs were validated by using GSE40595, involving 8 normal ovarian stroma, 31 ovarian cancer stroma, 6 human ovarian surface epthelium, and 32 ovarian tumor epthelial component. RESULTS: Between stage I/II/III/IV and control, 39/143/29/39 DEmiRNAs were identified, which were regarded as key miRNAs. Between 4 DEmiRNA sets, 15 common DEmiRNAs were identified (e.g. up-regulated hsa-miR-1181 and hsa-miR-4314). Hsa-miR-1181 participated in "Jak-STAT signaling pathway" and "miRNAs in cancer"; hsa-miR-4314 took part in cancer-related pathways. STAT3 and KRAS, known marker genes of ovarian cancer, were targeted by hsa-miR-1181 and hsa-miR-4314, respectively. Besides, FOXP1 was targeted by hsa-miR-1181; FOXP1-AS1 and FOXP1-IT1 were down-regulated in ovarian cancer. GRWD1, IP6K1, and NEGR1 were targeted by hsa-miR-4314; GRWD1, IP6K1, and NEGR1 were down-regulated in ovarian tumor. CONCLUSION: MiR-1181 and miR-4314 might promote ovarian tumorigenesis via down-regulating FOXP1 and GRWD1/IP6K1/NEGR1, respectively. In addition, the 15 common DEmiRNAs might provide directions for ovarian cancer diagnosis.

Analysis of methylation profiling data of hyperplasia and primary and metastatic endometrial cancers.

OBJECTIVE: Endometrial cancer is a prevalent cancer, and its metastasis causes low survival rate. This study aims to utilize DNA methylation data to investigate the mechanism of the development and metastasis of endometrial cancer. STUDY DESIGN: Methylation profiling data were down-loaded from Gene Expression Omnibus, including 8 hyperplasias, 33 primary and 53 metastatic endometrial cancers. COHCAP package and annotation files were utilized to identify differentially methylated genes (DMGs) and CpG islands between the three different endometrial diseases. STRING database and Cytoscape were used to analyze and visualize protein-protein interactions (PPIs) between DMGs. CytoNCA plugin was utilized to identify key nodes in PPI network. RESULTS: A total of 610, 1076, and 501 DMGs were identified between primary endometrial cancer and hyperplasia, metastatic endometrial cancer and hyperplasia, as well as metastatic and primary endometrial cancers, respectively. For the three DMG sets, 53 common hypermethylated DMGs (e.g. PAX6 and INSR) and 6 common hypomethylated DMGs (e.g. PRDM8, KLHL14, and DUSP6) were found. For primary-hyperplasia DMG set and metastasis-hyperplasia DMG set, 527 common DMGs were found. For these common DMGs, a PPI network involving 692 PPIs was constructed. For DMGs between metastatic and primary endometrial cancers, a PPI network involving 673 PPIs was established, with PAX6 and INSR in the top 20 DMGs in both networks. PRDM8, KLHL14, and DUSP6 had hypomethylated CpG islands. CONCLUSION: DMGs comparison, PPI network analysis, and analysis of differentially methylated CpG islands indicated that PAX6, INSR, PRDM8, KLHL14, and DUSP6 might participate in the development and metastasis of endometrial cancer.

Effect of a small dose of aspirin on quantitative test of 24-h urinary protein in patients with hypertension in pregnancy.

The aim of the present study was to determine the effect of a small dose of aspirin on a quantitative test of 24-h urinary protein in patients with hypertension in pregnancy. In total, 224 patients with hypertension in pregnancy were continuously selected and were randomly divided into the control group (50 cases with conventional therapy), aspirin 50 mg/day group (60 cases), aspirin 75 mg/day group (58 cases), and aspirin 100 mg/day group (56 cases). Clinical effects were compared from 16 gestational weeks to childbirth. According to the comparison in the four groups, there was no statistical difference in the mean arterial pressure, pre-eclampsia rate, gestational weeks, and caesarean section rate (p>0.05). The 24-h urinary protein and endothelin-1 (ET-1) level were significantly decreased following treatment, and were less than the control and 50 mg/day groups. The superoxide dismutase (SOD) level was significantly increased, and higher than the control and 50 mg/day groups. In terms of the 75 and 100 mg/day, control and 50 mg/day groups, there was no statistical difference (p>0.05). A comparison of the complication rate in the four groups of fetuses during the perinatal period, no statistical difference was observed (p>0.05). Thus, the results show that, regarding patients with hypertension in pregnancy, 75 mg/day aspirin can decrease the 24-h urinary protein, SOD, and ET-1 level. However, the results remain to be confirmed to improve maternal and infant outcome in delivery.

In search of key genes associated with endometriosis using bioinformatics approach.

OBJECTIVE: The aim of this study was to identify key genes associated with endometriosis. STUDY DESIGN: Microarray data GSE7846 was downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) in human endometrial endothelial cells derived from eutopic endometrium of patients with endometriosis compared with controls without endometriosis were identified using Linear Models for Microarray Data (LIMMA) package in R. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) enrichment analyses were performed using DAVID. Moreover, the protein-protein interaction (PPI) network was constructed by STRING and subsequently significantly enriched modules were mined by ClusterONE. Finally, protein domains and KEGG pathway enrichment analyses were performed for PPI modules. RESULTS: A total of 687 DEGs were identified, including 584 up- and 103 down-regulated genes. The up-regulated DEGs, such as epidermal growth factor (EGF) and interleukin 1 beta (IL-1ß) were significantly enriched in KEGG pathways of focal adhesion, ECM-receptor interaction and calcium signaling pathway. Similarly, only one module was obtained form PPI network, and the genes, like angiotensin II receptor, Type 1 (AGTR1) in the module were mainly enriched in protein domain of rhodopsin-like G protein-coupled receptors and most altered pathways of neuroactive ligand-receptor interaction, calcium signaling pathway and vascular smooth muscle contraction. CONCLUSIONS: Our findings indicate that EGF, IL-1ß and AGTR1 may play important roles in the pathogenesis of endometriosis.

Controllable fabrication of copper phthalocyanine nanostructure crystals.

Copper phthalocyanine (CuPc) nanostructure crystals, including nanoflower, nanoribbon, and nanowire, were controllably fabricated by temperature gradient physical vapor deposition (TG-PVD) through controlling the growth parameters. In a controllable growth system with carrier gas N2, nanoflower, nanoribbon, and nanowire crystals were formed in a high-temperature zone, medium-temperature zone, and low-temperature zone, respectively. They were proved to be ß-phase, coexist of α-phase and ß-phase, and α-phase respectively based on x-ray diffraction results. Furthermore, ultralong CuPc nanowires up to several millimeters could be fabricated by TG-PVD without carrier gas, and they were well-aligned to form large-area CuPc nanowire crystal arrays by the Langmuir-Blodgett method. The nanostructure crystals showed unusual optical absorption spectra from the ultraviolet-visible to near-infrared range, which was explained by the diffraction and scattering caused by the wavelength-sized nanostructures. These CuPc nanostructure crystals show potential applications in organic electronic and optoelectronic devices.

Poly(ADP-ribose) polymerase 1 promotes oxidative-stress-induced liver cell death via suppressing farnesoid X receptor α.

Farnesoid X receptor α (FXR) is highly expressed in the liver and regulates the expression of various genes involved in liver repair. In this study, we demonstrated that activated poly(ADP-ribose) polymerase 1 (PARP1) promoted hepatic cell death by inhibiting the expression of FXR-dependent hepatoprotective genes. PARP1 could bind to and poly(ADP-ribosyl)ate FXR. Poly(ADP-ribosyl)ation dissociated FXR from the FXR response element (FXRE), present in the promoters of target genes, and suppressed FXR-mediated gene transcription. Moreover, treatment with a FXR agonist attenuated poly(ADP-ribosyl)ation of FXR and promoted FXR-dependent gene expression. We further established the CCl4-induced acute liver injury model in wild-type and FXR-knockout mice and identified an essential role of FXR poly(ADP-ribosyl)ation in CCl4-induced liver injury. Thus, our results identified poly(ADP-ribosyl)ation of FXR by PARP1 as a key step in oxidative-stress-induced hepatic cell death. The molecular association between PARP1 and FXR provides new insight into the mechanism, suggesting that inhibition of PARP1 could prevent liver injury.

Poly(ADP-ribose) polymerase 1 is a key regulator of estrogen receptor α-dependent gene transcription.

Activation of nuclear receptor estrogen receptor α (ERα) exerts cardiovascular protective effects by modulating the expression of ERα target genes. However, the underlying mechanism remains unclear. PARP1 is a ubiquitous multifunctional nuclear enzyme. In this study, we examined the interplay between PARP1 and ERα, and identified PARP1 as an important regulator of ERα-dependent transcription. We showed that PARP1 could directly bind to ERα, and ERα could be poly(ADP-ribosyl)ated by PARP1. Poly(ADP-ribosyl)ation increased ERα binding to estrogen response element (ERE) present in the promoter of target genes and promoted ERα-mediated gene transcription. Estradiol, the ligand of ERα, increased PARP enzymatic activity and enhanced poly(ADP-ribosyl)ation of ERα. Upon treatment with estradiol, ERα binding to ERE- and ERα-dependent gene expression was dramatically increased in cultured vascular smooth muscle cells (VSMCs). Inhibition of PARP1 by PARP inhibitor or PARP1 siRNA decreased ERα binding to ERE and prevented ERα-dependent gene transcription in VSMCs. Further studies revealed that PARP1 served as an indispensible component for the formation of the ERα-ERE complex by directly interacting with ERα. Thus, our results identify PARP1 as a key regulator of ERα in controlling ERα transactivation.