Genomes, fossils, and the concurrent rise of modern birds and flowering plants in the Late Cretaceous.

The phylogeny and divergence timing of the Neoavian radiation remain controversial despite recent progress. We analyzed the genomes of 124 species across all Neoavian orders, using data from 25,460 loci spanning four DNA classes, including 5,756 coding sequences, 12,449 conserved nonexonic elements, 4,871 introns, and 2,384 intergenic segments. We conducted a comprehensive sensitivity analysis to account for the heterogeneity across different DNA classes, leading to an optimal tree of Neoaves with high resolution. This phylogeny features a novel Neoavian dichotomy comprising two monophyletic clades: a previously recognized Telluraves (land birds) and a newly circumscribed Aquaterraves (waterbirds and relatives). Molecular dating analyses with 20 fossil calibrations indicate that the diversification of modern birds began in the Late Cretaceous and underwent a constant and steady radiation across the KPg boundary, concurrent with the rise of angiosperms as well as other major Cenozoic animal groups including placental and multituberculate mammals. The KPg catastrophe had a limited impact on avian evolution compared to the Paleocene-Eocene Thermal Maximum, which triggered a rapid diversification of seabirds. Our findings suggest that the evolution of modern birds followed a slow process of gradualism rather than a rapid process of punctuated equilibrium, with limited interruption by the KPg catastrophe. This study places bird evolution into a new context within vertebrates, with ramifications for the evolution of the Earth's biota.

3DSNP 2.0: update and expansion of the noncoding genomic variant annotation database.

The rapid development of single-molecule long-read sequencing (LRS) and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) technologies presents both challenges and opportunities for the annotation of noncoding variants. Here, we updated 3DSNP, a comprehensive database for human noncoding variant annotation, to expand its applications to structural variation (SV) and to implement variant annotation down to single-cell resolution. The updates of 3DSNP include (i) annotation of 108 317 SVs from a full spectrum of functions, especially their potential effects on three-dimensional chromatin structures, (ii) evaluation of the accessible chromatin peaks flanking the variants across 126 cell types/subtypes in 15 human fetal tissues and 54 cell types/subtypes in 25 human adult tissues by integrating scATAC-seq data and (iii) expansion of Hi-C data to 49 human cell types. In summary, this version is a significant and comprehensive improvement over the previous version. The 3DSNP v2.0 database is freely available at https://omic.tech/3dsnpv2/.

Comparison of a novel hand-held retractor-assisted transforaminal lumbar interbody fusion by the wiltse approach and posterior TLIF: a one-year prospective controlled study.

BACKGROUND: This study aims to compare the clinical outcomes and safety of a novel hand-held retractor system-assisted Wiltse TLIF with that P-TLIF and assess whether this hand-held retractor system assisted Wiltse TLIF can yield less paraspinal muscle injury. METHODS: 56 patients (P-TLIF: 26, Wiltse TLIF: 30) were included in this one year prospective controlled study. The operation time, intraoperative blood loss, postoperative drainage, mobilization time, and discharge time were recorded. The clinical outcomes were evaluated by ODI, VAS, JOA, and SF-36 scores (7 days, 3, 6, and 12 months after surgery). Paraspinal muscle injury was assessed by postoperative MRI (6 months after surgery). CK and C-reaction protein were measured pre and postoperatively, and CT or X-ray (one year postoperatively) was used to assess bony union/non-union. RESULTS: The Wiltse (study) group was associated with significantly less estimated blood loss (79.67 ± 28.59 ml vs 192.31 ± 59.48 ml, P = 0.000*), postoperative drainage (43.33 ± 27.89 ml vs 285.57 ± 123.05 ml, P = 0.000*), and shorter mobilization (4.1 ± 1.2 d vs. 3.0 ± 0.9 d, P < 0.05) and discharge times (7.7 ± 1.9 d vs. 6.1 ± 1.2 d, P = 0.002*) than the P-TLIF (control) group. Serum CK activity at 24 h postoperatively in the study group was significantly lower than in the control group (384.10 ± 141.99 U/L vs 532.76 ± 225.76 U/L, P = 0.018*). At 7 days after surgery, VAS (2.3 ± 0.6 vs 3.2 ± 0.7, P = 0.000*)and ODI scores (43.9 ± 11.9 vs 55.2 ± 12.9, P = 0.001*) were lower, while the JOA scores (18.4 ± 3.4 vs 16.3 ± 4.2, P = 0.041*) was higher in the control group than in the study group. Results observed at 3 months of follow-up were consistent with those at 7 days. After six months postoperatively, paraspinal muscle degeneration in the control group was more significant than in the study group (P = 0.008*). CONCLUSION: Our study showed that this novel hand-held retractor system assisted Wiltse approach TLIF can significantly reduce paraspinal muscle injury, postoperative drainage, and intraoperative blood loss, mobilization and discharge time, as well as yield better short-term outcomes compared to P-TLIF. TRIAL REGISTRATION: 25/09/2023 NCT06052579.

High-Performance Macroporous Free-Standing Microbial Fuel Cell Anode Derived from Grape for Efficient Power Generation and Brewery Wastewater Treatment.

Microbial fuel cells (MFCs) have the potential to directly convert the chemical energy in organic matter into electrical energy, making them a promising technology for achieving sustainable energy production alongside wastewater treatment. However, the low extracellular electron transfer (EET) rates and limited bacteria loading capacity of MFCs anode materials present challenges in achieving high power output. In this study, three-dimensionally heteroatom-doped carbonized grape (CG) monoliths with a macroporous structure were successfully fabricated using a facile and low-cost route and employed as independent anodes in MFCs for treating brewery wastewater. The CG obtained at 900 °C (CG-900) exhibited excellent biocompatibility. When integrated into MFCs, these units initiated electricity generation a mere 1.8 days after inoculation and swiftly reached a peak output voltage of 658 mV, demonstrating an exceptional areal power density of 3.71 W m-2. The porous structure of the CG-900 anode facilitated efficient ion transport and microbial community succession, ensuring sustained operational excellence. Remarkably, even when nutrition was interrupted for 30 days, the voltage swiftly returned to its original level. Moreover, the CG-900 anode exhibited a superior capacity for accommodating electricigens, boasting a notably higher abundance of Geobacter spp. (87.1%) compared to carbon cloth (CC, 63.0%). Most notably, when treating brewery wastewater, the CG-900 anode achieved a maximum power density of 3.52 W m-2, accompanied by remarkable treatment efficiency, with a COD removal rate of 85.5%. This study provides a facile and low-cost synthesis technique for fabricating high-performance MFC anodes for use in microbial energy harvesting.

Use of plant growth regulators to reduce 2-methyl-4-chlorophenoxy acetic acid-Na (MPCA-Na) damage in cotton (Gossypium hirsutum).

BACKGROUND: 2-methyl-4-chlorophenoxy acetic acid-Na (MPCA-Na) is a phenoxy carboxylic acid selective hormone herbicide that is widely used in the crop fields. However, drift of MPCA-Na during application is highly damaging to cotton (Gossypium hirsutum) and other crop plants. This study was carried out from 2019 to 2020 to determine the effects of different concentrations of MPCA-Na on physiological and metabolic activities besides growth and yield of cotton plants at seedling, budding, flowering and boll stages. Moreover, we evaluated the different combinations of 24-epibrassinolide, gibberellin (GA3), phthalanilic acid and seaweed fertilizer to ameliorate herbicide damage. RESULTS: 2-methyl-4-chlorophenoxy acetic acid-Na (MPCA-Na) exposure caused a decrease in the chlorophyll content, and an increase in the soluble protein content, Malondialdehyde (MDA) content and protective enzyme activity. It also caused significant reductions in plant height, boll number and the single boll weight at the seedling and budding stages, but had little effects on plant height and the single boll weight at flowering and boll stage. Under the maximum recommended dose of MPCA-Na (130 g/L), the number of cotton bolls at seedling and budding stages decreased by 75.33 and 79.50%, respectively, and the single boll weight decreased by 46.42 and 36.31%, respectively. Nevertheless, the number of G. hirsutum bolls and single boll weight at flowering and boll stage decreased by 48.15 and 5.38%, respectively. Application of plant growth regulators decreased the MDA content, and increased chlorophyll, soluble protein content and protective enzyme activity, and alleviated MCPA-Na toxicity. Positive effects in case of growth regulators treated plants were also observed in terms of G. hirsutum yield. Phthalanilic acid + seaweed fertilizer, 24-epibrassinolide + seaweed fertilizer, and GA3 + seaweed fertilizer should be used at the seedling, budding, and flowering and boll stages, respectively. CONCLUSIONS: The results of current study suggest that certain plant growth regulators could be used to alleviate MPCA-Na damage and maintain G. hirsutum yield. When the cotton exposed to MCPA-Na at the seedling stage, it should be treated with phthalanilic acid + seaweed fertilizer, while plants exposed at the budding stage should be treated with 24-epibrassinolide + seaweed fertilizer, and those exposed at the flowering and boll stages should be treated with GA3 + seaweed fertilizer to mitigate stress.

The effects of mepiquat chloride (DPC) on the soluble protein content and the activities of protective enzymes in cotton in response to aphid feeding and on the activities of detoxifying enzymes in aphids.

BACKGROUND: Mepiquat chloride (DPC) enhances the resistance of cotton plants, and it is widely used as a growth regulator. DPC can stimulate photosynthesis, stabilize the structure of cotton leaves, and affect population reproduction and energy substances in Aphis gossypii Glover (cotton aphids), but interactions between DPC and cotton aphids remain unclear. In this study, we analyzed the physiological responses of cotton to DPC, and the toxicity of DPC toward cotton aphids, before and after feeding, to explore the DPC-induced defense mechanism against cotton aphids. RESULTS: Measurements of protective enzyme activity in cotton showed that the soluble protein contents, peroxidase (POD) activity, and catalase (CAT) activity in cotton treated with different concentrations of DPC were higher than in the control. Superoxide dismutase (SOD) activity was higher than that of the control when the concentration of DPC was < 0.1 g/L. Under aphid feeding stress, POD activity in cotton treated with a low insect population density was significantly lower than in the controls, but the reverse was true for cotton treated with a high insect population density, and SOD activity was positively correlated with population density. The activities of detoxification enzymes in field and laboratory experiments showed that DPC promoted the specific activity of glutathione S-transferase (GST) in cotton aphids, while the specific activities of carboxylesterase (CarE) and acetylcholinesterase (AchE) were decreased. CONCLUSIONS: DPC enhanced the aphid resistance in cotton by increasing the soluble protein content and the activity of protective enzymes. It also had a toxic effect on cotton aphids by increasing GST activity (the main DPC target). DPC increased the soluble protein content and protective enzymes activity in cotton under aphid stress, and thereby enhanced tolerance to cotton aphids. It conclude that DPC interferes with cotton aphids through indirect (DPC induced cotton defense responses) and direct (DPC toxicity to cotton aphids) ways, which plays a positive role in interfering with cotton aphids.

DeepHiC: A generative adversarial network for enhancing Hi-C data resolution.

Hi-C is commonly used to study three-dimensional genome organization. However, due to the high sequencing cost and technical constraints, the resolution of most Hi-C datasets is coarse, resulting in a loss of information and biological interpretability. Here we develop DeepHiC, a generative adversarial network, to predict high-resolution Hi-C contact maps from low-coverage sequencing data. We demonstrated that DeepHiC is capable of reproducing high-resolution Hi-C data from as few as 1% downsampled reads. Empowered by adversarial training, our method can restore fine-grained details similar to those in high-resolution Hi-C matrices, boosting accuracy in chromatin loops identification and TADs detection, and outperforms the state-of-the-art methods in accuracy of prediction. Finally, application of DeepHiC to Hi-C data on mouse embryonic development can facilitate chromatin loop detection. We develop a web-based tool (DeepHiC, http://sysomics.com/deephic) that allows researchers to enhance their own Hi-C data with just a few clicks.

Efficacy of Regional Anesthesia in Secondary Procedures or Revisions of Arteriovenous Fistula.

BACKGROUND: Several factors affect the outcomes of arteriovenous fistula (AVF) and end-stage renal disease (ESRD). This study aimed to evaluate the efficacy of regional anesthesia in secondary procedures or revisions of AVF. METHODS: Medical records of patients who underwent treatment for AVF secondary procedures or revisions under brachial plexus block (BPB) between March 2016 and June 2019 were retrospectively analyzed. Patient characteristics and clinical outcomes were evaluated. RESULTS: In total, 375 patients (mean age 65.6 ± 12.74; males 210, 56.0%) were enrolled in the study and 770 procedures were performed under BPB for AVF secondary procedures or revisions. The procedures included endovascular treatment (385, 50.0%), surgical treatment (105, 13.6%), and hybrid treatment (280, 36.4%). In 180 procedures (23.4%) for AVF lesions, the operative field included a single segment of the arm, whereas in 590 procedures (76.6%), the operative field included multiple segments. In total, 37 (4.8%) cases of 30-day postoperative complications were observed, of which 33 (4.3%) were surgery-related complications, 2 (0.3%) were BPB-related complications (neurapraxia), and 2 (0.3%) were contrast agent allergic reactions; 34 (4.4%) reinterventions of the total 201 (26.1%) reinterventions were performed within 30 days postoperatively. The mean operation time was 87.5 ± 55.35 min. The pain score for all patients was 0 (no pain), and no patient demanded opioids postoperatively. CONCLUSIONS: Ultrasound-guided BPB is safe and effective for AVF secondary procedures or revisions in ESRD patients.

Effects of carvedilol and metoprolol on the myocardium during mechanical unloading in a rat heterotopic heart transplantation model.

BACKGROUND AND OBJECTIVES: Left ventricular assist devices enable recovery from severe heart failure and serve as a bridge to heart transplantation. However, chronic mechanical unloading can impair myocardial recovery. We aimed to assess myocyte size, fibrosis, apoptosis, and ß-adrenoreceptor levels after rats with left ventricle unloading induced by heterotopic heart transplantation were administered carvedilol and metoprolol. METHODS: Thirty rats with heart transplants were divided randomly into control, carvedilol treatment, and metoprolol treatment groups. Follow-up was conducted after 2 and 4 weeks of unloading. RESULTS: Carvedilol and metoprolol treatments did not prevent the decrease in myocyte diameter in unloaded left ventricles. Metoprolol significantly decreased the ratio of the fibrotic area in the unloaded heart, measured using Masson's trichrome staining after 2 weeks. However, carvedilol and metoprolol did not reduce apoptosis, based on measurements of terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labelling positive cells and the expression of caspase-3 in unloaded hearts after 2 and 4 weeks. Metoprolol treatment did not significantly decrease the mRNA expression of myocardial SERCA2a in the unloaded heart after 2 weeks. CONCLUSIONS: Compared to carvedilol treatment, metoprolol treatment improved myocardial fibrosis and SERCA2a expression to a greater extent; however, neither drug prevented myocardial apoptosis.

Psoriatic lesions are characterized by higher bacterial load and imbalance between Cutibacterium and Corynebacterium.

BACKGROUND: Several studies have found that the microbiota of psoriatic lesions is different from that of healthy skin. OBJECTIVE: To characterize the microbiota of lesional and unaffected skin in patients with psoriasis and controls and investigate the correlation between cutaneous microbiota and clinical features of psoriasis. METHODS: Using quantitative polymerase chain reaction and 16S rRNA sequencing, we assayed the profiles of cutaneous microbiota in controls, unaffected skin, and psoriatic lesions. We also investigated the correlation of psoriasis-associated taxa with clinical characteristics. RESULTS: High bacterial load was identified in the psoriatic lesions compared with unaffected skin and controls. There was an imbalance between Cutibacterium (also known as Propionibacterium) and Corynebacterium in psoriatic skin. Lesions showed a higher proportion of Corynebacterium and a lower proportion of Cutibacterium compared with unaffected skin and controls. Corynebacterium was correlated with the severity of local lesions, whereas Cutibacterium showed correlation with the abnormity of skin capacitance. LIMITATIONS: We did not conduct a longitudinal study. CONCLUSIONS: Psoriatic lesions are characterized by higher bacterial load and imbalance between Cutibacterium and Corynebacterium.

Adipose-derived mesenchymal stem cells ameliorate the inflammatory reaction in CLP-induced septic acute lung injury rats via sTNFR1.

We hypothesized that the adipose-derived mesenchymal stem cells (ADMSCs), which secrete high amounts of soluble molecules, such as soluble tumor necrosis factor receptor 1 (sTNFR1), may ameliorate sepsis-induced acute lung injury (ALI). A total of 120 male adult Sprague-Dawley rats were separated into four groups: the sham control (SC), sepsis induced by cecal ligation and puncture (CLP), CLP-ADMSCs, and CLP-sTNFR1 small interfering RNA (siRNA) groups; CLP groups underwent CLP and then received 1 × 106 ADMSCs with or without knockdown of sTNFR1 intravenously at 1 hr after surgery. Rats were killed at 3, 6, 24, and 48 hr after the SC or CLP procedures. 5-Ethynyl-2'-deoxyuridine-labeled ADMSCs extensively colonized the lungs at 6, 24, and 72 hr after injection. The lung wet/dry (W/D) weight ratios in the CLP group were higher than those in SC group; however, ADMSCs ameliorated the W/D weight ratios following CLP, and this effect was abolished by sTNFR1 siRNA treatment. The levels of serum sTNFR1 and interleukin-10 (IL-10) were higher in the CLP-ADMSCs group and lower in the SC group than in other groups; interestingly, these levels were higher in CLP and CLP-sTNFR1 siRNA groups than in SC group. Tumor necrosis factor-α and IL-6 levels increased significantly after CLP, and ADMSCs could alleviate these changes, but the effect was weakened by sTNFR1 siRNA treatment. The lung cell apoptosis and edema levels were consistent with IL-6 levels among all groups. Therapeutically administered ADMSCs secrete sTNFR1, which most likely protects against ALI in septic rats by ameliorating inflammation and lung edema.

In vitro selection of aptamer S1 against MCF-7 human breast cancer cells.

Breast cancer is the most common female cancer. However, the known effective specific biomarkers for breast cancer are still scarce. Abnormal membrane proteins serve as ideal biomarkers for disease diagnoses, therapeutics and prognosis. Thus aptamers (single-stranded oligonucleotide molecules) with molecular recognition properties can be used as efficient tools to sort cells based on differences in cell surface architecture between normal and tumor cells. In this study, we aimed to screen specific aptamer against MCF-7 human breast cancer cells. Cell-SELEX process was performed to isolate aptamers from a combinatorial single-stranded nucleic acid library that selectively targeting surface proteins of MCF-7 cells in contrast with MCF-10A human mammary epithelial cells. The process was repeated until the pool was enriched for sequences that specifically recognizing MCF-7 cells in monitoring by flow cytometry. Subsequently, the enriched pool was cloned into bacteria, and positive clones were sequenced to obtain individual sequences. Representative sequences were chemically synthesized and evaluated their binding affinities to MCF-7 cells. As a result, an aptamer S1 was finally identified to have high binding affinity with equilibrium dissociation constant (Kd) value of 29.9 ±â€¯6.0 nM. FAM-labeled aptamer S1 induced fluorescence shift in MCF-7 cells but not in MCF-10A human mammary epithelial cells, or MDA-MB-453 and MDA-MB-231 human breast cancer cells. Furthermore, result of cell imaging observed from laser confocal fluorescence microscope showed that MCF-7 cells exhibited stronger fluorescence signal resulted from Cy5-labeled aptamer S1 than MCF-10A cells. The above findings suggested that S1 may be a specificity and selectivity aptamer for MCF-7 cells and useful for the breast cancer detection and diagnosis.

3DSNP: a database for linking human noncoding SNPs to their three-dimensional interacting genes.

The vast noncoding portion of the human genome harbors a rich array of functional elements and disease-causing regulatory variants. Recent high-throughput chromosome conformation capture studies have outlined the principles of these elements interacting and regulating the expression of distal target genes through three-dimensional (3D) chromatin looping. Here we present 3DSNP, an integrated database for annotating human noncoding variants by exploring their roles in the distal interactions between genes and regulatory elements. 3DSNP integrates 3D chromatin interactions, local chromatin signatures in different cell types and linkage disequilibrium (LD) information from the 1000 Genomes Project. 3DSNP provides informative visualization tools to display the integrated local and 3D chromatin signatures and the genetic associations among variants. Data from different functional categories are integrated in a scoring system that quantitatively measures the functionality of SNPs to help select important variants from a large pool. 3DSNP is a valuable resource for the annotation of human noncoding genome sequence and investigating the impact of noncoding variants on clinical phenotypes. The 3DSNP database is available at http://biotech.bmi.ac.cn/3dsnp/.

O-linked GlcNAcylation elevated by HPV E6 mediates viral oncogenesis.

High-risk human papillomaviruses (HPVs) are causative agents of anogenital cancers and a fraction of head and neck cancers. The mechanisms involved in the progression of HPV neoplasias to cancers remain largely unknown. Here, we report that O-linked GlcNAcylation (O-GlcNAc) and O-GlcNAc transferase (OGT) were markedly increased in HPV-caused cervical neoplasms relative to normal cervix, whereas O-GlcNAcase (OGA) levels were not altered. Transduction of HPV16 oncogene E6 or E6/E7 into mouse embryonic fibroblasts (MEFs) up-regulated OGT mRNA and protein, elevated the level of O-GlcNAc, and promoted cell proliferation while reducing cellular senescence. Conversely, in HPV-18-transformed HeLa cervical carcinoma cells, inhibition of O-GlcNAc with a low concentration of a chemical inhibitor impaired the transformed phenotypes in vitro. We showed that E6 elevated c-MYC via increased protein stability attributable to O-GlcNAcylation on Thr58. Reduction of HPV-mediated cell viability by a high concentration of O-GlcNAc inhibitor was partially rescued by elevated c-MYC. Finally, knockdown of OGT or O-GlcNAc inhibition in HeLa cells or in TC-1 cells, a mouse cell line transformed by HPV16 E6/E7 and activated K-RAS, reduced c-MYC and suppressed tumorigenesis and metastasis. Thus, we have uncovered a mechanism for HPV oncoprotein-mediated transformation. These findings may eventually aid in the development of effective therapeutics for HPV-associated malignancies by targeting aberrant O-GlcNAc.

Histone Modifications Regulate the Developmental Expression of Human Hepatic UDP-Glucuronosyltransferase 1A1.

Human UDP-glucuronosyltransferase 1A1 (UGT1A1) is a unique enzyme involved in bilirubin conjugation. We previously characterized the hepatic expression of transcription factors affecting UGT1A1 expression during development. Accordingly, in this study, we characterized the ontogenetic expression of hepatic UGT1A1 from the perspective of epigenetic regulation. We observed significant histone-3-lysine-4 dimethylation (H3K4me2) enrichment in the adult liver and histone-3-lysine-27 trimethylation (H3K27me3) enrichment in the fetal liver, indicating that dynamic alterations of histone methylation were associated with ontogenetic UGT1A1 expression. We further showed that the transcription factor hepatocyte nuclear factor 1α (HNF1A) affects histone modifications around the UGT1A1 locus. In particular, we demonstrated that by recruiting HNF1A the cofactors mixed-lineage leukemia 1, the transcriptional coactivator p300, and nuclear receptor coactivator 6 aggregate at the UGT1A1 promoter, thereby regulating histone modifications and subsequent UGT1A1 expression. In this study, we proposed new ideas for the developmental regulation of metabolic enzymes via histone modifications, and our findings will potentially contribute to the development of age-specific therapies.

Hepatic expression of transcription factors affecting developmental regulation of UGT1A1 in the Han Chinese population.

PURPOSE: Complete or partial inactivity of UGT1A1, the unique enzyme responsible for bilirubin glucuronidation, is commonly associated with hyperbilirubinemia. We investigated the dynamic expression of UGT1A1, and that of the transcription factors (TFs) involved in its developmental regulation, during human hepatic growth in Han Chinese individuals. METHODS: Eighty-eight prenatal, pediatric, and adult liver samples were obtained from Han Chinese individuals. Quantitative real-time polymerase chain reaction was used to evaluate mRNA expression of UGT1A1 and TFs including PXR, CAR, HNF1A, HNF4A, PPARA, etc. UGT1A1 protein levels and metabolic activity were determined by western blotting and high-performance liquid chromatography. Direct sequencing was employed to genotype UGT1A1*6 (211G˃A) and UGT1A1*28 (TA6˃TA7) polymorphisms. RESULTS: UGT1A1 expression was minimal in prenatal samples, but significantly elevated during pediatric and adult stages. mRNA and protein levels and metabolic activity were prominently increased (120-, 20-, and 10-fold, respectively) in pediatric and adult livers compared to prenatal samples. Furthermore, expression did not differ appreciably between pediatric and adult periods. Dynamic expression of TFs, including PXR, CAR, HNF1A, HNF4A, and PPARA, was consistent with UGT1A1 levels at each developmental stage. A pronounced correlation between expression of these TFs and that of UGT1A1 (P < 0.001) was observed. Moreover, UGT1A1*6 and UGT1A1*28 polymorphisms reduced levels of UGT1A1 by up to 40-60 %. CONCLUSIONS: Hepatic expression of transcription factors is associated with developmental regulation of UGT1A1 in the Han Chinese population. Moreover, UGT1A1 polymorphisms are associated with reduced expression of UGT1A1 mRNA and protein, as well as enzyme activity.