The evaluation of catechins reducing heterocyclic aromatic amine formation: Structure-activity relationship and mechanism speculation.

The favorable inhibitory effect of tea polyphenols on heterocyclic aromatic amines (HAAs) has been confirmed in many past studies. The objective of this study was to investigate the structure-activity relationship of catechins that act as inhibitors of HAA formation in chemical models. Two kinds of quantitative structure-activity relationship models for catechin-inhibiting-HAA were established. We chose two kinds of HAAs including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and five catechins including epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC), epicatechin (EC), and catechin (C). The inhibitory effect of five catechins were in the following order: EGCG > ECG > EGC > C > EC. Thereinto, EGCG and ECG showed dramatically better inhibition on the formation of PhIP and MeIQx, especially EGCG. Further, the mechanisms of catechin-inhibiting-HAA were speculated by correlation analysis. The free radical-scavenging ability was predicted to be the most relevant to the inhibitory effect of ECG, EGC, EC and C on HAAs. Differently, the phenylacetaldehyde-trapping ability might be the more important mechanism of EGCG inhibiting PhIP in chemical model system. This study may bring a broader idea for controlling the formation of HAAs according to the structure of catechins.

A systematic study on the chemical model of polycyclic aromatic hydrocarbons formation from nutrients (glucose, amino acids, fatty acids) in food.

Polycyclic aromatic hydrocarbons (PAHs), prominent carcinogens formed during food processing, pose health risks through long-term consumption. This study focuses on 16 priority PAHs in the European Union, investigating their formation during pyrolysis. Glucose, amino acids and fatty acids are important food nutrients. To further explore whether these nutrients in food form PAHs during heating, a single chemical model method was used to heat these nutrients respectively, and GC-MS/MS was used to identify and quantify the obtained components. Glucose is the most basic nutrient in food, so the influence of water, pH, temperature and other factors on the formation of PAHs was studied in the glucose model. At the same time, the models of amino acids and fatty acids were used to assist in improving the entire nutrient research system. According to our results, some previously reported mechanisms of PAHs formation by fatty acids heating were confirmed. In addition, glucose and amino acids could also produce many PAHs after heating, and some conclusions were improved by comparing the intermediates of PAHs from three types of nutrients.

Exploring the roles of excess amino acids, creatine, creatinine, and glucose in the formation of heterocyclic aromatic amines by UPLC-MS/MS.

The prevention and control of heterocyclic aromatic amines (HAA) formation to mitigate of potential risks to humans, can be achieved by targeting their precursors. In this study, the detailed roles of individual and excess component (20 common α-amino acids, creatine, creatinine, and glucose) on HAA formation in roasted beef patties were examined using UPLC-MS/MS. The results confirmed the reported classical precursors of HAAs. Some components regulated the competitive production of Norharman and Harman. Glycine (Gly) and glucose favored Norharman formation, while cysteine (Cys) and phenylalanine (Phe) for Harman. Serine (Ser) and threonine (Thr) were identified as potential precursors for IQx-type HAAs. Interestingly, methionine (Met), Gly, Thr, Cys, alanine (Ala), and Ser were revealed as more targeted underlying precursors for 1,6-DMIP and 1,5,6-TMIP, and the formation mechanism was inferred. Furthermore, Pro, Leu, His, Ile, Lys and Asp were considered as great inhibitors for HAAs.

Bioinformatics-based Identification of Ferroptosis-Related Genes and their Diagnostic Value in Gestational Diabetes Mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is considered a risk factor for heart metabolic disorder in future mothers and offspring. Ferroptosis is a new type of programmed cell death, which may participate in the occurrence and development of GDM. OBJECTIVE: This study aims to identify ferroptosis-related genes in GDM by bioinformatics methods and to explore their clinical diagnostic value. METHODS: The dataset GSE103552 was analyzed using the Gene Expression Omnibus (GEO) database to screen for differentially expressed genes (DEGs) in GDM. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and proteinprotein interaction (PPI) network were performed. Gene sets for ferroptosis were retrieved in MSigDB and GSVA gene set analysis was performed on the database. Finally, logistic regression was performed to differentiate between GDM patients and controls to screen for diagnostic markers. RESULTS: A total of 179 DEGs were identified in the expression profile of GDM. GO and KEGG enrichment analysis revealed significant enrichment in the TGF-ß, p53 signaling pathway, platelet activation, glutathione metabolism, sensory perception of taste, and leukocyte and vascular endothelial cell migration regulation. DEGs (n = 107) associated with the ferroptosis gene set were screened by GSVA analysis. The screened DEGs for disease and DEGs for ferroptosis scores were intersected and 35 intersected genes were identified. PPI identified two key genes associated with GDM as CCNB2 and CDK1. Wilcox-test showed low expression of CCNB2 and CDK1 in GDM. The area under the ROC curve (AUC) of the CCNB2 and CDK1 prognostic model was 0.822. CONCLUSION: The genes associated with ferroptosis in GDM were CCNB2 and CDK1, which can be used as valid indicators for the diagnosis of GDM.

Investigating the Potential Mechanisms of Ferroptosis and Autophagy in the Pathogenesis of Gestational Diabetes.

Ferroptosis and autophagy are two different cellular processes that have recently been highlighted for their potential roles in the pathogenesis and progression of gestational diabetes (GD). This research sought to uncover the crucial genes tied to ferroptosis and autophagy in GD, further investigating their mechanisms. Differentially expressed genes (DEGs) linked to ferroptosis and autophagy in GD were identified using publicly available data. Pathway enrichment, protein interactions, correlation with immune cell infiltration, and diagnostic value of DEGs were analyzed. HTR-8/SVneo cells were subjected to varying glucose levels to evaluate cell viability and the expression of markers related to ferroptosis and proteins associated with autophagy. Crucial DEGs were validated in vitro. A total of 12 DEGs associated with ferroptosis and autophagy in GD were identified, enriched in the PI3K-AKT signaling pathway. These genes exhibited significant correlations with monocyte infiltration, resting CD4 memory T cells, and follicular helper T cells. They exhibited high diagnostic value for GD (AUC: 0.77-0.97). High glucose treatment inhibited cell viability, induced ferroptosis, and activated autophagy in HTR-8/SVneo cells. Validation confirmed altered expression of SNCA, MTDH, HMGB1, TLR4, SOX2, SESN2, and HMOX1 after glucose treatments. In conclusion, ferroptosis and autophagy may play a role in GD development through key genes (e.g., TLR4, SOX2, SNCA, HMOX1, HMGB1). These genes could serve as promising biomarkers for GD diagnosis.

Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Ischemic Stroke Within 4.5 Hours of Stroke Onset: A Phase 3 Randomized Clinical Trial.

Importance: Recombinant human prourokinase (rhPro-UK) is a thrombolytic agent that has shown promising findings in a phase 2 clinical trial in patients with acute ischemic stroke (AIS). Objective: To evaluate the efficacy and safety of rhPro-UK thrombolysis within 4.5 hours of symptom onset in patients with AIS. Design, Setting, and Participants: This randomized, alteplase-controlled, open-label, phase 3 clinical trial was conducted from May 2018 to May 2020 at 35 medical centers in China. A total of 684 patients were screened and 674 patients were enrolled. Included patients were aged 18 to 80 years with a diagnosis of AIS and received treatment within 4.5 hours of stroke onset. Data were analyzed from June to October 2020. Interventions: Eligible patients were randomly assigned (1:1) to receive intravenous rhPro-UK or alteplase. Main Outcomes and Measures: The primary objective was to assess whether rhPro-UK was noninferior to alteplase. The noninferiority margin was a between-group difference of less than 10%. The primary outcome was a modified Rankin Scale score of 0 to 1 at 90 days. Results: Among 663 patients in the modified intention-to-treat population (mean [SD] age, 61.00 [10.20] years; 161 females [24.3%]), there were 330 patients in the rhPro-UK group and 333 patients in the alteplase group. The median (IQR) baseline National Institutes of Health Stroke Scale score was 6.00 (5.00-9.00). There were 23 deaths, and 619 patients (93.4%) completed the 3-month follow-up. The primary outcome occurred in 215 patients (65.2%) in the rhPro-UK group and 214 patients (64.3%) in the alteplase group (risk difference, 0.89; 95.4% CI, -6.52 to 8.29). Symptomatic intracerebral hemorrhage occurred in 5 patients (1.5%) in the rhPro-UK group and 6 patients (1.8%) in the alteplase group (P > .99). Systemic bleeding within 90 days occurred more frequently in the alteplase group (141 patients [42.2%]) than the rhPro-UK group (85 patients [25.8%]) (P < .001). By 90 days, 5 thrombolysis-related deaths each had occurred in the rhPro-UK group (1.5%) and alteplase group (1.5%) (P > .99). Conclusions and Relevance: This study found that intravenous rhPro-UK within 4.5 hours of AIS onset was noninferior to alteplase. The rhPro-UK group showed a similar rate of symptomatic ICH but fewer cases of systemic bleeding than the alteplase group. Trial Registration: ClinicalTrials.gov Identifier: NCT03541668.

Discovery of novel hydroxyamidine based indoleamine 2,3-dioxygenase 1 (IDO1) and thioredoxin reductase 1 (TrxR1) dual inhibitors.

In order to take advantage of both immunotherapeutic and metabolic antitumor agents, novel dual indoleamine 2,3- dioxygenase 1 (IDO1) and thioredoxin reductase 1 (TrxR1) inhibitors were designed. Thioredoxin reductase 1 (TrxR1) is a main ROS modulator within CRC cells. Indoleamine 2,3-dioxygenase (IDO1) is crucial controller for tryptophan (Trp) metabolism that is also important for CRC immunotherapy. Herein, ten compounds 12a-j containing hydroxyamidine scaffold were designed, synthesized and evaluated for inhibitory activities against IDO1/TrxR1 enzyme and CRC cells. Among these compounds, the most active compound 12d (ZC0109) showed excellent and balanced activity against both IDO1 (IC50 = 0.05 µM) and TrxR1 (IC50 = 3.00 ± 0.25 µM) were selected for further evaluation. Compound ZC0109 exhibited good dual inhibition against IDO1 and TrxR1 both in vitro and in vivo. Further mechanistic studies reveal that, through IDO1 and TrxR1 inhibition by ZC0109 treatment, accumulated ROS effectively induced apoptosis and G1/S cell cycle arrest in cancer cells. In vivo evaluation demonstrated excellent anti-tumor effect of ZC0109 with the notable ability of promoting ROS-induced apoptosis, reducing kynurenine level in plasma and restoring anti-tumor immune response. Thus, ZC0109 represents a potential CRC therapy agent for further development.

Risk Factors Associated With Lower Bone Mineral Density in Primary Aldosteronism Patients.

Purpose: The association between primary aldosteronism (PA) and lower bone mineral density (BMD) has raised a concern, but the contributing factors remain unclear. We aim to explore the risk factors for lower BMD in PA patients. Methods: We analyzed and compared the data of 60 PA patients with 60 matched essential hypertension (EH) patients. BMD, bone metabolites, and several oxidative stress and inflammation indicators-including C-reactive protein (CRP), superoxide dismutase (SOD), total bilirubin (TBIL), mean platelet volume (MPV), etc.-were assessed and compared in PA and EH patients. Bivariate correlation analysis and multivariate linear regression analysis were performed to explore the factors associated with BMD in PA patients. Results: The BMD measured by quantitative computed tomography in PA patients was lower than that in EH patients (141.9 ± 34.0 vs. 158.9 ± 55.9 g/cm3, p = 0.047), especially in patients less than 50 years old. BMD was independently negatively associated with age (standardized ß = -0.581, p < 0.001), serum phosphorus (standardized ß = -0.203, p = 0.008), urinary calcium excretion (standardized ß = -0.185, p = 0.031), and MPV (standardized ß = -0.172, p = 0.043) and positively associated with SOD (standardized ß = 0.205, p = 0.011) and TBIL (standardized ß = 0.212, p = 0.015). Conclusions: The PA patients showed a lower BMD than the EH patients, which was associated with age, serum phosphorus, urinary calcium excretion, MPV, SOD, and TBIL. These variables might be potential markers for the assessment of bone loss and efficacy of treatments in PA patients.

The strategy for estrogen receptor mediated-risk assessment in environmental water: A combination of species sensitivity distributions and in silico approaches.

Risk assessment for molecular toxicity endpoints of environmental matrices may be a pressing issue. Here, we combined chemical analysis with species sensitivity distributions (SSD) and in silico docking for multi-species estrogen receptor mediated-risk assessment in water from Dongjiang River, China. The water contains high levels of phenolic endocrine-disrupting chemicals (PEDCs) and phthalic acid esters (PAEs). The concentration of ∑4PEDCs and ∑6PAEs ranged from 2202 to 3404 ng/L and 834-4368 ng/L, with an average of 3241 and 2215 ng/L, respectively. The SSD approach showed that 4-NP, BPA, E2 of PEDCs, and DBP, DOP, and DEHP could severely threaten the aquatic ecosystems, while most other target compounds posed low-to-medium risks. Moreover, binding affinities from molecular docking among PEDCs, PAEs, and estrogen receptors (ERα, Erß, and GPER) were applied as toxic equivalency factors. Estrogen receptor-mediated risk suggested that PEDCs were the main contributors, containing 53.37-69.79% of total risk. They potentially pose more severe estrogen-receptor toxicity to zebrafish, turtles, and frogs. ERß was the major contributor, followed by ERα and GPER. This study is the first attempt to assess the estrogen receptor-mediated risk of river water in multiple aquatic organisms. The in silico simulation approach could complement toxic effect evaluations in molecular endpoints.

Interleukin-17 promotes proliferation, migration, and invasion of trophoblasts via regulating PPAR-γ/RXR-α/Wnt signaling.

To investigate the effect of Interleukin 17 (IL-17) on the invasive capacity of trophoblast cells and the underlying mechanism, we collected placental tissues samples from pregnant women with preeclampsia (PE) and healthy pregnant women. The expression levels of IL-17 mRNA and protein in tissue samples were determined using qRT-PCR and Western blot, respectively. Cell viability and cell proliferation was determined using CCK-8 assay, and colony formation assay, respectively. Cell migration and invasion capacity were determined using transwell cell migration assay. Our results showed that the mRNA expression of IL-17 was significantly increased in PE patients and may be used as a sensitive biomarker for PE (P < 0.01). IL-17 overexpression promoted cell viability, migration, and invasion of human extravillous trophoblast cell line, HTR8/SVneo; however, IL-17 knockdown inhibited these effects. Additionally, IL-17 activated PPAR-γ/RXR-α signaling pathway, which promoted proliferation, migration, and invasion of trophoblast cells. Moreover, PPAR-γ/RXR-α heterodimers activated Wnt signaling. In conclusion, our study provides evidence that IL-17 is overexpressed in PE and promotes proliferation, migration and invasion of trophoblast cells via activating PPAR-γ/RXR-α/Wnt signaling.

Ecological and AhR-mediated risk assessment of polycyclic aromatic hydrocarbons and polybrominated diphenyl ethers on multiple aquatic species in river water: A combined chemical analysis and in silico approach.

Assessing the adverse health risks at molecular endpoints to various aquatic organisms could be an urgent issue. In this manuscript, the ecological and AhR-mediated risk of sixteen polycyclic aromatic hydrocarbons (PAHs) and six polybrominated diphenyl ethers (PBDEs) in surface water of Dongjiang River, Southern China was evaluated using chemical analysis and in silico approaches. Average concentrations of ∑16PAHs and ∑6PBDEs were 586.3 ng/L and 2.672 ng/L in the dry season (DS), and 366.8 ng/L and 2.554 ng/L in the wet season (WS). Concentrations of PAHs during the DS were significantly higher than that in the WS, while no obvious seasonal distribution was observed for PBDEs. Only Ant and BaP in all congers of PAHs posed low to medium ecological risks, and PBDEs posed a low ecological risk. Moreover, AhR-mediated risk from PAHs was two orders of magnitude higher that from PBDEs, and the AhR-mediated toxicity on frog and eel were higher than those on other aquatic organisms in Dongjiang River. Phe and BDE209 were the significant contributor to the AhR-mediated risk induced by PAHs and PBDEs, respectively. This study is the first attempt to assess AhR-mediated risk of river water in multiple aquatic organisms.

Complete mitochondrial genomes of two catfishes (Siluriformes, Bagridae) and their phylogenetic implications.

The mitochondrial genome (mitogenome) has been widely used as a molecular marker to investigate phylogenetic analysis and evolutionary history in fish. However, the study of mitogenomes is still scarce in the family Bagridae. In this study, the mitogenomes of Tachysurusbrachyrhabdion and T.gracilis were sequenced, annotated, and analyzed. The mitogenomes were found to be 16,532 bp and 16,533 bp, respectively, and each contained 37 typical mitochondrial genes, which are 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and a control region. All PCGs begin with the codon ATG, except for the cytochrome c oxidase subunit 1 (COI) gene, while seven PCGs end with an incomplete termination codon. All tRNA genes can fold into their typical cloverleaf secondary structures, except for tRNASer(AGY), which lacks the dihydrouracil arm. The Ka/Ks ratios for all PCGs are far lower than one. Phylogenetic analyses based on Bayesian inference (BI) and maximum likelihood (ML) showed that the two clades in Bagridae excluded Ritarita. The monophyly of Tachysurus supports previous research and the traditional classification that Leiocassis, Pseudobagrus, Pelteobagrus, and Tachysurus belong to one genus (Tachysurus). These findings provide a phylogenetic basis for future phylogenetic and taxonomic studies of Bagridae.

Discovery of hydroxytyrosol as thioredoxin reductase 1 inhibitor to induce apoptosis and G1/S cell cycle arrest in human colorectal cancer cells via ROS generation.

Colorectal cancer (CRC) is one of the most common cancer types and a leading cause of cancer-associated mortality in China. Increased thioredoxin reductase 1 (TrxR1) levels have been previously identified as possible target for CRC. The present study revealed that the natural product hydroxytyrosol (HT), which exhibits a polyphenol scaffold, is a potent inhibitor of TrxR1. Inhibition of TrxR1 was indicated to result in accumulation of reactive oxygen species, inhibit proliferation and induce apoptosis and G1/S cell cycle arrest of CRC cells. Using a C-terminal mutant TrxR1 enzyme activity assay, TrxR1 RNA interference assay and HT binding model assay, the present study demonstrated the core character of the selenocysteine residue in the interaction between HT and TrxR1. HT can serve as polyphenol scaffold to develop novel TrxR1 inhibitors for CRC treatment in the future.

Assessment of epigenotoxic profiles of Dongjiang River: A comprehensive of chemical analysis, in vitro bioassay and in silico approach.

This research explored the occurrence, epigenetic toxic profiling and main toxic pollutants of POPs in surface water of Dongjiang River, southern China. The concentrations of selected POPs including polycyclic aromatic hydrocarbons (PAHs), endocrine disrupting chemicals (EDCs), phthalate esters (PAEs) and polybrominated diphenyl ethers (PBDEs) of surface water from 18 sites were investigated. ∑16PAHs and ∑4EDCs were at a moderate level, while ∑6PAEs and ∑6PBDEs had low pollution levels. PAHs, EDCs and PAEs showed higher concentrations in dry season than those in wet season, and the loading of selected POPs in tributaries was higher than those in mainstream due to intensive manufactures and lower runoff volume. Moreover, activities of DNA methyltransferase (DNMT)1, histone deacetylase (HDAC2, HDAC8) were confirmed to be sensitive indicators for epigenetic toxicity. The DNMT1-mediated epigenetic equivalency toxicity of organic extracts in Dongjiang River were more serious than those of HDAC2 and HDAC8. Correlation analysis shown binding affinity between POPs and DNMT1, HDAC2 and HDAC8 could be regarded as toxic equivalency factors. Risk assessment suggested that 4-nonylphenol and bisphenol A were the largest contributors to epigenetic risk. This study is the first attempt to quantify epigenetic toxicity and epigenetic risk evaluation of river water.

Dichlorodiphenyltrichloroethane metabolites inhibit DNMT1 activity which confers methylation-specific modulation of the sex determination pathway.

Dichlorodiphenyltrichloroethane (DDT) poses a significant health risk to humans which is associated with genomic DNA hypomethylation. However, the mechanism and biological consequences remain poorly understood. In vitro assays confirmed that the DDT metabolites 2,2-bis(p-chlorophenyl)-acetic acid (DDA) and 1-chloro-2,2-bis-(p-chlorophenyl)ethylene (DDMU), but not other DDT metabolites, significantly inhibited DNA methyltransferase 1 (DNMT1) activity, leading to genomic hypomethylation in cell culture assays. DNMT1 as a target for DNA hypomethylation induced by DDT metabolites was also confirmed using cell cultures in which DNMT1 was silenced or highly expressed. DDA and DDMU can modify methylation markers in the promoter regions of sexual development-related genes, and change the expression of Sox9 and Oct4 in embryonic stem cells. Molecular docking indicated that DDA and DDMU bound to DNMT1 with high binding affinity. Molecular dynamic simulation revealed that DDA and DDMU acted as allosteric modulators that reshaped the conformation of the catalytic domain of DNMT1. These findings provide a new insight into DDT-induced abnormalities in sexual development and demonstrate that selective binding to DNMT1 by DDA and DDMU can interfere with human DNMT1 activity and regulate the expression of the Sox9 and Oct4 genes.

In situ assessment of genetic and epigenetic alterations in frog Rana plancyi and Rana limnocharis inhabiting aquatic ecosystems associated with Pb/Zn/Cu mining.

Exploration for metallic minerals leads to severe trace metal contamination, thus the ecological risk to aquatic organisms near mining regions has attracted widespread attention. In this study, two species of frog Rana plancyi and Rana limnocharis were collected as amphibian models to explore the genetic and epigenetic effects of trace metals in Dexing mining region. The results indicated that the surface water was heavily contaminated with trace metals and the two species of frog have high bioconcentration of trace metals in the liver. Trace metals disrupted the redox balance and increased reactive oxygen species levels. DNA strand breaks and increased 8-hydroxy-2'-deoxyguanosine levels were observed in the genomic DNA of frogs. Global DNA hypomethylation was found in the liver, which indicated adverse epigenetic effects on frogs. Overall, the study demonstrated that there was significant genotoxicity and epigenotoxicity of aquatic organisms living around the mining region. DNA damage and global DNA methylation are promising biomarkers for assessment of the ecological risk of trace metal pollution in aquatic amphibian frogs.

Rapid photolysis of H2S and the mechanism using high-frequency discharge electrodeless lamp.

In the present study, the H2S photolysis using the self-made high-frequency discharge electrodeless lamp (light distribution was 90% at 254 nm and 10% at 185 nm) was studied and simulated by MATLAB software. Firstly, the effects of the initial H2S concentration, irradiation time, oxygen content and relative humidity on H2S photolysis efficiency were experimentally investigated. The results indicated that the photolysis efficiency decreased from 100% to 90.13% with the increase in the initial concentration from 3 to 30 mg/m3, and the main product was H2SO4. With the relative humidity increased from 0% to 99%, H2S photolysis efficiency was obviously improved under different atmospheres (O2 > air > Ar), indicating the significant effect of relative humidity and oxygen concentration. The simulation results were consistent with the experimental results, indicating the feasibility of the simulation model. Moreover, based on the photoreactions, model simulation and equilibrium analysis of sulphur species, the photodegradation pathway of H2S was further inferred. H2S was oxidized to H2SO4 by O3 and other strong oxidizing radicals excited by 185 nm UV light.

Metal contamination, bioaccumulation, ROS generation, and epigenotoxicity influences on zebrafish exposed to river water polluted by mining activities.

Epigenetic mechanisms are important for gene expression regulation, which is closely related to human health, and epigenetic effects of polluted water bodies have gained increasing research attention. Le'an River suffers from severe trace metal pollution owing to mining activities. In this study, zebrafish was used as a biological model to study pollution of Le'an River after seven consecutive days of exposure. The results showed that midstream and downstream sections of the river were seriously polluted by trace metals. The liver and gill of zebrafish were enriched with trace metals, and cadmium had the highest bioaccumulation factor. Trace metals caused oxidative stress in zebrafish cells, with increases in reactive oxygen species levels. Significant increase of global DNA methylation in liver of middle and downstream section were observed, with values from 125.67% to 165.45% compared with control. Changes in DNA methylation in the promoter region cause significant increase or decrease of the expression of repair genes and apoptosis genes in liver and gill. In summary, Le'an River water exhibited significant epigenetic effects, and it is necessary to consider epigenetic effects in the evaluation of pollution and health risks of river water.

Pregnancy-induced Cushing's syndrome with an adrenocortical adenoma overexpressing LH/hCG receptors: a case report.

BACKGROUND: Pregnancy-induced Cushing's syndrome (CS) with an adrenocortical adenoma overexpressing luteinizing hormone (LH)/human choriogonadotropin (hCG) receptors (LHCGR) has been rarely reported in the literatures. This peculiar condition challenges the canonical diagnosis and management of CS. CASE PRESENTATION: A 27-year-old woman (G2P0A1) presented at 20 weeks gestational age (GA) with overt Cushingoid clinical features. Adrenocorticotropic hormone (ACTH)-independent CS was diagnosed based on undetectable ACTH and unsuppressed cortisol levels by dexamethasone. Magnetic resonance imaging (MRI) scanning without contrast revealed a left adrenal nodule while pituitary MRI scanning was normal. A conservative treatment strategy of controlling Cushingoid comorbidities was conducted. At 36 weeks GA, a caesarean operation was performed and a live female infant was delivered. At 8 weeks after parturition, our patient achieved normalization of blood pressure, blood glucose, serum potassium, and urinary cortisol level spontaneously. During non-pregnancy period, stimulation testing with exogenous hCG significantly evoked a cortisol increase. The woman underwent resection of the adrenal tumor at 6 months after parturition. Immunohistochemistry (IHC) showed the tumor tissue that stained positive for luteinizing hormone (LH)/human choriogonadotropin (hCG) receptor (LHCGR), whereas negative for both melanocortin 2 receptor (MC2R) and G protein-coupled receptor-1 (GPER-1). CONCLUSIONS: Stimulation test with exogenous hCG after parturition is necessary for the diagnosis of pregnancy-induced CS. LHCGR plays an essential role in the pathogenesis of this rare condition.

Operation performance and microbial community of sulfur-based autotrophic denitrification sludge with different sulfur sources.

Operation performance and bacterial community structure of sulfur-based autotrophic denitrification (SAD) based on different sulfur sources served as electron donor was first parallelly compared among three sequencing batch reactors. Sulfur and sodium thiosulfate systems achieved similar operation performance and were superior to that of sodium sulfide. When the influent NO3--N concentration ranged from 50 to 150 mg/L, the effluent NO3--N concentrations of the sulfur and sodium thiosulfate systems were 0-5.99 mg/L and 0-4.52 mg/L, respectively, without NO2--N accumulation. However, when the effluent concentration of NO3--N in the sodium sulfide system was 0-10.38 mg/L, that of NO2--N in the effluent was 0-39.85 mg/L. In addition, participation of sulfur sources presented obvious pressure on the bacterial community structure based on the high-throughput sequencing. Microbial diversity results indicated that sludge with elemental sulfur as electron donor had the richest microbial diversity, followed by sodium thiosulfate and sodium sulfide. Moreover, sludge with elemental sulfur and sodium thiosulfate as electron donor demonstrated more similar community structure compared with the sludge that denitrified with sodium sulfide according to the microbial similarity analysis. The 9.34%, 24.3% and 29.6% of sequences could be assigned to potential SAD organisms from sludge denitrifying with elemental sulfur, sodium thiosulfate and sodium sulfide, respectively. Furthermore, all sludge denitrifying with different sulfur sources showed an enrichment of separate core functional microorganisms. This study could provide an insight into improving the understanding of SAD in engineering applications.