lhCLIP reveals the in vivo RNA-RNA interactions recognized by hnRNPK.

RNA-RNA interactions play a crucial role in regulating gene expression and various biological processes, but identifying these interactions on a transcriptomic scale remains a challenge. To address this, we have developed a new biochemical technique called pCp-biotin labelled RNA hybrid and ultraviolet crosslinking and immunoprecipitation (lhCLIP) that enables the transcriptome-wide identification of intra- and intermolecular RNA-RNA interactions mediated by a specific RNA-binding protein (RBP). Using lhCLIP, we have uncovered a diverse landscape of intermolecular RNA interactions recognized by hnRNPK in human cells, involving all major classes of noncoding RNAs (ncRNAs) and mRNA. Notably, hnRNPK selectively binds with snRNA U4, U11, and U12, and shapes the secondary structure of these snRNAs, which may impact RNA splicing. Our study demonstrates the potential of lhCLIP as a user-friendly and widely applicable method for discovering RNA-RNA interactions mediated by a particular protein of interest and provides a valuable tool for further investigating the role of RBPs in gene expression and biological processes.

Assessment of Human Exposure to Traditional and Novel Organophosphate Esters via Multiple Personal Matrices.

Herein, 16 traditional and 13 novel organophosphate esters (OPEs) in skin wipes, personal PM2.5, sputum, and nails (fingernails and toenails) and 7 OPE metabolites in urine synchronously obtained from 64 college students were analyzed. Similar compositional profiles of the OPEs were found in skin wipes and nails and in personal PM2.5 and induced sputum. Significant correlations were observed between the concentrations of high-lipophilicity low-volatility OPEs in skin wipes and nails and between the concentrations of high-volatility low-lipophilicity OPEs in personal PM2.5 and sputum. These results imply that OPEs in fingernails and toenails may mainly come from external sources rather than internal exposure, and human nails and sputum can be used as indicators of human exposure to OPEs. A comparison between the daily exposure doses of the OPEs in personal PM2.5 and sputum shows that more volatile compounds may have higher inhalation bioavailability, which should be considered to improve the accuracy of inhalation exposure assessments. According to comprehensive external and internal exposure assessment, dermal absorption may be a more dominant pathway than inhalation, and skin wipes may be the best representative environmental matrix of human exposure to OPEs.

Fasting serum fructose is associated with metabolic dysfunction-associated fatty liver disease: A prospective study.

AIM: The association between sugar-sweetened beverages and metabolic disorders has been well studied. However, it has not been determined whether fasting serum fructose is associated with metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: Participants were enrolled from 2011 to 2012 in Shanghai. Fasting serum fructose concentration was measured with a validated liquid chromatography-tandem mass spectrometry method. RESULTS: A total of 954 participants without diabetes were included. They were followed for an average of 3.5 years. A total of 320 (33.5%) participants had MAFLD at baseline. With the increase in fasting serum fructose level by quartile, the MAFLD prevalence was increased by 27.0%, 25.0%, 37.4%, and 44.5%, respectively (p < 0.001). Each SD increase in fasting serum fructose level was associated with a 60% increased risk of MAFLD (odds ratio 1.60; 95% confidence interval [CI], 1.36-1.88; p < 0.001). Fasting serum fructose levels were more closely associated with four components of MAFLD (hepatic steatosis, prediabetes, insulin resistance, and low high-density lipoprotein). We built a diagnostic model named the fructose fat index (FFI). The area under the receiver operating characteristic curve of the FFI was 0.879 (95% CI, 0.850-0.908) in the derivation cohort and 0.827 (95% CI, 0.776-0.878) in the validation cohort. Subsequent prospective studies found that the incidence risk of MAFLD was 2.26 times higher in the high-fructose group than in the low-fructose group among female participants (95% CI, 1.46-3.49; p < 0.001). CONCLUSION: Fasting serum fructose concentration, which mostly reflects endogenous fructose, was associated with a higher risk of MAFLD. The FFI derived from fasting serum fructose could be used to predict MAFLD.

A systematic characterization of soil/dust ingestion for typical subpopulations in China.

An accurate assessment of human exposure to pollutants through the ingestion of dust and/or soil particles depends on a thorough understanding their rate of human ingestion. To this end, we investigated the load and size distribution patterns of dust/soil particles on the hands of three typical subpopulations, including preschoolers, college students, and security guards (outdoor workers). The geometric mean diameter of dust/soil particles on hands was observed to be 38.7 ± 11.2, 40.0 ± 12.1, and 36.8 ± 10.4 µm for preschoolers, college students, and security guards, respectively. The particle size distribution differed between subpopulations: Preschoolers were more exposed to fine particles, whereas security guards were exposed to more coarse particles. The geometric means of dust/soil particle loading on the hands were 0.126, 0.0163, and 0.0377 mg/cm2 for preschoolers, college students, and security guards, respectively. Males had statistically higher dust/soil particle loadings on hands than females, notably for preschoolers and college students; preschoolers with frequent hand contact with the bare ground had higher dust/soil particle loadings compared to those of peers in contact with commercial and residential grounds. The mean total dust/soil particle ingestion rate was estimated to be 245, 19.7, and 33.1 mg/day for preschoolers, college students, and security guards, respectively. Our estimates for college students and security guards are close to the consensus central-tendency values recommended by the U.S. EPA's Exposure Factor Handbook for American adults, whereas the estimates for children are much higher than the upper percentile values recommended for American children.

Phloretin ameliorates diabetes-induced endothelial injury through AMPK-dependent anti-EndMT pathway.

Diabetic cardiovascular complications contribute more than half of diabetes mortality. Endothelial damage and subsequent pathological changes play a key role in this process. Phloretin, a plant-derived dihydrochalcone compound, was reported to have the activities in regulating metabolism homeostasis and anti-inflammation. However, its effects and the mechanism on early stage endothelial injury caused by diabetes are not clear yet. In our present study, human umbilical vein endothelial cells (HUVECs) were stimulated by high glucose or advanced glycation end products (AGEs) to induce endothelial damage, and streptozotocin (STZ) -induced diabetes mouse model was used for in vivo study. Our results showed that phloretin effectively reduced endothelial damage marker monocyte chemotactic protein-1 (MCP1) as well as pro-calcification factors bone morphogenetic protein-2 (BMP2) and receptor activator of NF-κB ligand (RANKL) expression, reversed the increased vimentin and decreased CD31 dose-dependently in vitro and in vivo. Phloretin had no effect on blood glucose level. However, it ameliorated endothelial injury and vascular fibrosis in diabetic mice. Further experiments revealed that phloretin could enhance AMP activated protein kinase (AMPK) activation and upregulate peroxidase proliferator activated receptor-gamma coactivator-lα (PGC1α) level, and inhibit the activation of TGFß-Smad2-Snail signalling pathway which was abrogated by AMPK inhibitor, providing a rational mechanism that AMPK activation was required for the effects of phloretin on endothelial injury and endothelial-mesenchymal transformation (EndMT). Our data reveal a new role of phloretin in protection of diabetic endothelial damage via AMPK-dependent anti-EndMT activation, and also provide a potential therapeutic way for diabetic endothelial damage and its subsequent cardiovascular complications.

"Two-birds-one-stone" colon-targeted nanomedicine treats ulcerative colitis via remodeling immune microenvironment and anti-fibrosis.

Dysregulated mucosal immune responses and colonic fibrosis impose two formidable challenges for ulcerative colitis treatment. It indicates that monotherapy could not sufficiently deal with this complicated disease and combination therapy may provide a potential solution. A chitosan-modified poly(lactic-co-glycolic acid) nanoparticle (CS-PLGA NP) system was developed for co-delivering patchouli alcohol and simvastatin to the inflamed colonic epithelium to alleviate the symptoms of ulcerative colitis via remodeling immune microenvironment and anti-fibrosis, a so-called "two-birds-one-stone" nanotherapeutic strategy. The bioadhesive nanomedicine enhanced the intestinal epithelial cell uptake efficiency and improved the drug stability in the gastrointestinal tract. The nanomedicine effectively regulated the Akt/MAPK/NF-κB pathway and reshaped the immune microenvironment through repolarizing M2Φ, promoting regulatory T cells and G-MDSC, suppressing neutrophil and inflammatory monocyte infiltration, as well as inhibiting dendritic cell maturation. Additionally, the nanomedicine alleviated colonic fibrosis. Our work elucidates that the colon-targeted codelivery for combination therapy is promising for ulcerative colitis treatment and to address the unmet medical need.

Mechanistic examination of methimazole-induced hepatotoxicity in patients with Grave's disease: a metabolomic approach.

Methimazole (MMI), the first-line anti-thyroid agent used in clinical practice is known to induce hepatotoxicity in patients with Grave's disease (GD), although its exact mechanism remains largely unclear. This cohort study aimed to examine the mechanism of MMI-induced hepatotoxicity using metabolomic approach. A total of 40 GD patients with MMI-induced hepatotoxicity (responders) and 80 GD patients without MMI-induced hepatotoxicity (non-responders) were included in this study and their plasma metabolomics was profiled with targeted gas chromatography-tandem mass spectrometry (GC-MS/MS). The plasma levels of 42 metabolites, including glucuronic acid, some amino acids, fatty acids, ethanolamine and octopamine were found to be significantly different between responders and non-responders. In agreement with our previous genotyping data, the genetic polymorphism of uridine 5'-diphospho-glucuronosyltransferase (UGT)1A1*6, which affects the glucuronidation activity and circulating glucuronic acid level was identified as one of the determinants of MMI-induced hepatotoxicity. Plasma level of ethanolamine has a significant correlation with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. The pathway analyses further revealed that monoamine oxidase (MAO) inhibition, reactive oxygen species (ROS) production, mitochondria dysfunction, and DNA disruption might contribute to MMI-induced hepatotoxicity. Interestingly, the metabolomic data further suggested the responders had a higher risk of developing osteoporosis and fatty liver disease in comparison to the non-responders. This mechanistic study sheds light on the pathogenesis of MMI-induced hepatotoxicity and prompts personalized prescription of MMI based on UGT1A1*6 genotype in the management of GD.

Blue- and green-emitting hydrophobic carbon dots: preparation, optical transition, and carbon dot-loading.

In the past decade, hydrophobic fluorescent carbon dots (OCDs) have received little attention, and its potential application and light transition mechanism is seldom explored. Here we report a novel one-step approach for synthesizing blue- and green-emitting hydrophobic fluorescent carbon dots (OCDb and OCDg) by calcinating with the uses of citric acid and hexadecylamine as initial reactants. The optimal conditions for preparing OCDb and OCDg were obtained by using the Taguchi L25 (35) orthogonal array. The highest quantum yield and product yield of OCDs reached 80.2% and 57.1%, respectively, larger than those from most of all the known reports. The fluorescent stability of OCDb and OCDg was excellent under UV irradiation (30 W) for days. The luminescent color of OCDs showed a great dependence on reaction conditions. It is easier to get OCDg via a reaction kept at a high temperature for a long time. The optical transition mechanism was studied for the two kinds of color OCDs, and therefore proposed in combination with their optical properties and surface groups. The reason for light transition is probably related to an appropriate critical ratio and surface density of the C=O and N-H bond in the surface structure of the product. For the OCDg, the concentration matching ratio of N-H and C=O bonds in the surface structure of the green-emitting product is approximately between d/2 and 3d/2, where d is a fixed constant. Lower than or higher than this critical ratio range, the product emits blue light. Based on their high fluorescence quantum efficiency and the advantages mentioned above, these OCDs were then respectively used for preparing hydrophobic fluorescent carbon dot-loading liposomes and acrylate films, both exhibiting a perfect performance with no fluorescence quenching.

Metabolic characteristics of Tanshinone I in human liver microsomes and S9 subcellular fractions.

Tanshinone I (TSI) is a lipophilic diterpene in Salvia miltiorrhiza with versatile pharmacological activities. However, metabolic pathway of TSI in human is unknown. In this study, we determined major metabolites of TSI using a preparation of human liver microsomes (HLMs) by HPLC-UV and Q-Trap mass spectrometer. A total of 6 metabolites were detected, which indicated the presence of hydroxylation, reduction as well as glucuronidation. Selective chemical inhibition and purified cytochrome P450 (CYP450) isoform screening experiments revealed that CYP2A6 was primarily responsible for TSI Phase I metabolism. Part of generated hydroxylated TSI was glucuronidated via several glucuronosyltransferase (UGT) isoforms including UGT1A1, UGT1A3, UGT1A7, UGT1A9, as well as extrahepatic expressed isoforms UGT1A8 and UGT1A10. TSI could be reduced to a relatively unstable hydroquinone intermediate by NAD(P)H: quinone oxidoreductase 1 (NQO1), and then immediately conjugated with glucuronic acid by a panel of UGTs, especially UGT1A9, UGT1A1 and UGT1A8. Additionally, NQO1 could also reduce hydroxylated TSI to a hydroquinone intermediate, which was immediately glucuronidated by UGT1A1. The study demonstrated that hydroxylation, reduction as well as glucuronidation were the major pathways for TSI biotransformation, and six metabolites generated by CYPs, NQO1 and UGTs were found in HLMs and S9 subcellular fractions.

Different effects of ursodeoxycholic acid on intrahepatic cholestasis in acute and recovery stages induced by alpha-naphthylisothiocyanate in mice.

The aim of this study was to determine the effect of ursodeoxycholic acid (UDCA) on the alpha-naphthylisothiocyanate (ANIT)-induced acute and recovery stage of cholestasis model mice. In the acute stage of model mice, pretreatment with UDCA (25, 50, and 100 mg·kg-1, ig) for 12 days prior to ANIT administration (50 mg·kg-1, ig) resulted in the dramatic increase in serum biochemistry, with aggrevation of bile infarcts and hepatocyte necrosis. The elevation of beta-muricholic acid (ß-MCA), cholic acid (CA), and taurocholic acid (TCA) in serum and liver, and reduction of these bile acids (BAs) in bile was observed. In contrast, in the recovery stage of model mice, treatment with UDCA (25, 50, and 100 mg·kg-1, ig) for 7 days after ANIT administration (50 mg·kg-1, ig) resulted in the significant decrease in levels of serum alanine aminotransferase (ALT) and total bile acid (TBA). Liver injury was attenuated, and the levels of TBA, CA, TCA, and ß-MCA in the liver were significantly decreased. Additionally, UDCA can upregulate expression of BSEP, but it cannot upregulate expression of AE2. UDCA, which induced BSEP to increase bile acid-dependent bile flow, aggravated cholestasis and liver injury when the bile duct was obstructed in the acute stage of injury in model mice. In contrast, UDCA alleviated cholestasis and liver injury induced by ANIT when the obstruction was improved in the recovery stage.

Sensitive and simultaneous surface plasmon resonance detection of free and p53-bound MDM2 proteins from human sarcomas.

Murine double minute 2 (MDM2) is an oncoprotein mediating the degradation of the tumor suppressor p53 protein. The physiological levels of MDM2 protein are closely related to malignant transformation and tumor growth. In this work, the simultaneous and label-free determination of free and p53-bound MDM2 proteins from sarcoma tissue extracts was conducted using a dual-channel surface plasmon resonance (SPR) instrument. Free MDM2 protein was measured in one fluidic channel covered with the consensus double-stranded (ds)-DNA/p53 conjugate, while MDM2 bound to p53 was captured by the consensus ds-DNA immobilized onto the other channel. To achieve higher sensitivity and to confirm specificity, an MDM2-specific monoclonal antibody (2A10) was used to recognize both the free and p53-bound MDM2 proteins. The resultant method afforded a detection limit of 0.55 pM of MDM2. The amenability of the method to the analysis of free and p53-bound MDM2 proteins was demonstrated for normal and sarcoma tissue extracts from three patients. Our data reveal that both free and total MDM2 (free and bound forms combined) proteins from sarcoma tissue extracts are of much higher concentrations than those from normal tissue extracts and the p53-bound MDM2 protein only constitutes a small fraction of the total MDM2 concentration. In comparison with enzyme-linked immunosorbent assay (ELISA), the proposed method possesses higher sensitivity, is more cost-effective, and is capable of determining free and p53-bound MDM2 proteins in clinical samples.

Charactering the metabolism of cryptotanshinone by human P450 enzymes and uridine diphosphate glucuronosyltransferases in vitro.

Cryptotanshinone (CT) is the main active component in the root of Salvia miltiorrhiza Bunge (SMB) that displays antibacterial, anti-inflammatory and anticancer activities. In this study, we characterized phase I and phase II metabolism of CT in human liver microsomes in vitro and identified the metabolic enzymes (CYPs and UGTs) involved. The metabolites of CT generated by CYPs were detected using LC-MS/MS and the CYP subtypes involved in the metabolic reactions were identified using chemical inhibitors of CYP enzymes and recombinant human CYP enzymes (CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). Glucuronidation of CT was also examined, and the UGT subtypes involved in the metabolic reactions were identified using recombinant human UGT enzymes (1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B15 and 2B17). After adding NADPH to the human liver microsomes incubation system, CT was transformed into 6 main dehydrogenation and hydroxylation metabolites. CYP2A6, CYP3A4 and CYP2C19 were the major contributors to the transformation of its hydroxylation metabolites. CYP2C19, CYP1A2 and CYP3A4 were the major contributors to the transformation of its hydrogenation metabolites in human liver microsomes. This study showed that the metabolites at m/z of 473 were mediated by UGT1A9 and that the metabolites at m/z of 489 were mediated by UGT2B7 and UGT2B4. CT was extensively metabolized by UGTs following metabolism by CYPs in the liver.

[Seroepidemiological survey of Toxoplasma gondii in dogs in Urumqi].

From 2011 to 2012 in Urumqi, blood samples of 308 household dogs and of 110 stray dogs were collected from three pet hospitals and a stray dog shelter, respectively. Serum anti-Toxoplasma gondii IgG was detected by ELISA. The results showed that the overall seropositive rate was 31.8% (133/418). The rate in household dogs and stray dogs was 29.9% (92/308) and 37.3% (41/110), respectively (P>0.05). Among 308 household dogs, the positive rate in males and females was 27.0% (41/152) and 32.7% (51/156), respectively (P>0.05). The seropositive rate in dogs <1 years old, 1-2 years old, and more than 2 years old was 27.1% (32/118), 30.2% (29/96), and 33.3% (31/94), respectively (P>0.05). The results revealed a high seroprevalence of T. gondii infection in dogs in Urumqi.

A Current Understanding of FXR in NAFLD: The multifaceted regulatory role of FXR and novel lead discovery for drug development.

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has reached 30 %, with an annual increase. The incidence of NAFLD-induced cirrhosis is rapidly rising and has become the leading indicator for liver transplantation in the US. However, there are currently no US Food and Drug Administration-approved drugs for NAFLD. Increasing evidence underscores the close association between NAFLD and bile acid metabolism disorder, highlighting the feasibility of targeting the bile acid signaling pathway for NAFLD treatment. The farnesoid X receptor (FXR) is an endogenous receptor for bile acids that exhibits favorable effects in ameliorating the metabolic imbalance of bile acids, lipid disorders, and disruption of intestinal homeostasis, all of which are key characteristics of NAFLD, making FXR a promising therapeutic target for NAFLD. The present review provides a comprehensive overview of the diverse mechanisms through which FXR improves NAFLD, with particular emphasis on its involvement in regulating bile acid homeostasis and the recent advancements in drug development targeting FXR for NAFLD treatment.

Global patterns of human exposure to flame retardants indoors.

To fill the knowledge gaps regarding the global patterns of human exposure to flame retardants (FRs) (i.e., brominated flame retardants (BFRs) and organophosphorus flame retardants (OPFRs)), data on the levels and distributions of FRs in external and internal exposure mediums, including indoor dust, indoor air, skin wipe, serum and urine, were summarized and analysed. Comparatively, FR levels were relatively higher in developed regions in all mediums, and significant positive correlations between FR contamination and economic development level were observed in indoor dust and air. Over time, the concentration of BFRs showed a slightly decreasing trend in all mediums worldwide, whereas OPFRs represented an upward tendency in some regions (e.g., the USA and China). The occurrence levels of FRs and their metabolites in all external and internal media were generally correlated, implying a mutual indicative role among them. Dermal absorption generally contributed >60% of the total exposure of most FR monomers, and dust ingestion was dominant for several low volatile compounds, while inhalation was found to be negligible. The high-risk FR monomers (BDE-47, BDE-99 and TCIPP) identified by external exposure assessment showed similarity to the major FRs or metabolites observed in internal exposure mediums, suggesting the feasibility of using these methods to characterize human exposure and the contribution of indoor exposure to the human burden of FRs. This review highlights the significant importance of exposure assessment based on multiple mediums for future studies.

Short-hairpin RNA-mediated suppression of cortactin may inhibit the migration and invasion abilities of endometrial cancer cells by reducing lamellipodia.

Objectives: The prognosis of endometrial cancer (EC) is significantly affected by tumor infiltration and metastasis. Cortactin (CTTN) regulates infiltration and metastasis in other tumors. Studies on the role and mechanism of CTTN in EC are limited and further studies are needed. Materials and Methods: Quantitative PCR and immunohistochemistry were used to detect Ras-associated C3 botulinum toxin substrate 1 (Rac1) and CTTN in EC and normal tissues. The relationship between the expression of these two genes and their prognostic factors was analyzed. A CTTN-RNAi lentiviral system was constructed and transfected into EC cells. Migration and invasion were evaluated by scratch assay, transwell migration, and invasion assays. Pseudopodia formation was observed by immunofluorescence staining. Western blotting was performed to detect the expression of Rac1. Results: The expression levels of Rac1 and CTTN in EC tissues were significantly higher than those in normal tissues. In the EC group, Rac1 and CTTN levels were correlated. The protein expression levels of Rac1 and CTTN were related to myometrial invasion and stage. After CTTN knockdown, the migration rate, invasiveness, and migratory ability of EC cells decreased significantly. Lamellipodia was observed to disappear with the appearance of blebs. Rac1 protein expression was decreased after CTTN knockdown. Conclusion: CTTN may promote the invasion and migration of EC by lamellipodia. This effect may be related to the regulation of Rac1 by CTTN.

The contribution of IL-17A-dependent low LCN2 levels to Helicobacter pylori infection: Insights from clinical and experimental studies.

BACKGROUND: Helicobacter pylori (H. pylori) infection is a common bacterial infection that is widespread globally. It is crucial to comprehend the molecular mechanisms that underlie the infection caused by H. pylori in order to devise successful therapeutic approaches. The objective of this study was to examine the involvement of Lipocalin-2 (LCN2) in the development of H. pylori infection. METHODS: LCN2 expression levels in human gastric mucosa and H. pylori-infected mouse models were analyzed using quantitative PCR and immunohistochemistry methods. The effects of LCN2 on the attachment of H. pylori to gastric mucosa cells were assessed using bacterial culture and fluorescence intensity tests. To investigate the correlation between LCN2, CCL20, and IL-17A, we performed gene expression analysis and measured serum levels. RESULTS: The findings indicated an increase in LCN2 levels in the gastric mucosa of both patients and mice infected with H. pylori. Blocking the natural LCN2 resulted in an increased attachment of H. pylori to cells in the gastric mucosa. In addition, we noticed that reduced levels of LCN2 promoted the attachment of H. pylori to cells in the gastric mucosa. Furthermore, H. pylori-infected patients exhibited increased expression of both LCN2 and CCL20, and there was a positive correlation between serum levels of CCL20 and LCN2. LCN2 expression was found to depend on the presence of IL-17A, and inhibiting IL-17A led to a higher H. pylori colonization. CONCLUSION: The persistence of H. pylori infection is facilitated by the presence of low levels of LCN2, which is dependent on IL-17A. This finding offers valuable perspectives for the development of novel therapeutic approaches for H. pylori infection.

Occurrences of typical PPCPs during wastewater treatment and the composting of sewage sludge with micron-sized and nano-sized Fe3O4.

New pollutants, pharmaceuticals and personal care products (PPCPs), accumulate in sewage sludge (SS) in wastewater treatment plants (WWTPs), posing risks to the environment and to human health. In the present study, the fates of typical PPCPs, carbamazepine (CBZ), triclosan (TCS), ibuprofen (IBU) and galaxolide (HHCB), were examined during WW treatment. Additionally, SS collected from a WWTP was used for aerobic composting to investigate the influences of micron-sized Fe3O4 (M-Fe) and nano-sized Fe3O4 (N-Fe) on the degradation of these PPCPs and the succession of microbial communities during the composting process. The results showed that the mean concentrations of CBZ, TCS, IBU and HHCB in the influent of the WWTP were 926.5, 174.4, 8869, and 967.3 ng/g, respectively, and in the effluent were 107.6, 47.0, 283.4, and 88.4 ng/g, respectively. The removal rate averaged ∼80%, while the enrichment rates of the PPCPs in SS ranged from 37.2% to 60.5%. M-Fe and N-Fe reduced NH3 emissions by 32.9% and 54.1% and N2O emissions by 26.2% and 50.8%, respectively. Moreover, the addition of M-Fe and N-Fe effectively increased PPCP degradation rates 1.12-1.66-fold. During the whole process, the additions of M-Fe and N-Fe significantly shifted microbial community structure, and the abundances of Proteobacteria, Chloroflexi, and Actinobacteria were increased during the thermophilic stage, marking them as key PPCP-degrading phyla. Taken together, our results indicated that the addition of M-Fe and N-Fe is an effective method for improving the quality of end compost and accelerating the degradation of PPCPs.

The change of non-alcoholic fatty liver disease is associated with risk of incident diabetes.

Background & aims: The effect of change in non-alcoholic fatty liver disease (NAFLD) status on incident diabetes has not been well studied. We aimed to investigate the association of NAFLD development and remission with the risk of incident diabetes during a median of 3.5-year follow-up. Methods: A total of 2690 participants without diabetes were recruited in 2011-2012 and assessed for incident diabetes in 2014. Abdominal ultrasonography was used to determine the change of NAFLD. 75 g oral glucose tolerance test (OGTT) was performed to determine diabetes. NAFLD severity was assessed using Gholam's model. The odds ratios (ORs) for incident diabetes were estimated by logistic regression models. Results: NAFLD was developed in 580 (33.2%) participants and NAFLD remission occurred in 150 (15.9%) participants during a median of 3.5-year follow-up. A total of 484 participants developed diabetes during follow-up, including 170 (14.6%) in consistent non-NAFLD group, 111 (19.1%) in NAFLD developed group, 19 (12.7%) in NAFLD remission group, and 184 (23.2%) in sustained NAFLD group. The development of NAFLD increased the risk of incident diabetes by 43% (OR, 1.43; 95%CI, 1.10-1.86) after adjustment for multiple confounders. Compared with sustained NAFLD group, remission of NAFLD reduced the risk of incident diabetes by 52% (OR, 0.48; 95%CI, 0.29-0.80). The effect of NAFLD alteration on incident diabetes was not changed after adjustment for body mass index or waist circumference, change of body mass index or waist circumference. In NAFLD remission group, participants with non-alcoholic steatohepatitis (NASH) at baseline were more likely to develop diabetes (OR, 3.03; 95%CI, 1.01-9.12). Conclusions: NAFLD development increases the risk of incident diabetes, whereas NAFLD remission reduces the risk of incident diabetes. Moreover, presence of NASH at baseline could attenuate the protective effect of NAFLD remission on incident diabetes. Our study suggests that early intervention of NAFLD and maintenance of non-NAFLD are important for prevention of diabetes.