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Observations of microplastic particles (MPs) in the environment and their detection in the stomachs and intestines of aquatic organisms have been observed routinely over the last 50 years. In this review, the ingestion of plastic debris of varying sizes is collated, including data for >800 species representing approximately 87,000 individual organisms, for which plastic debris and MPs are observed in about 17,500 or 20%. The average of reported MP/individual across all studies is estimated at 4, with studies typically reporting averages ranging between 0 and 10 MP/individual. A general observation is that while strong evidence exists for the biological ingestion of MPs, they do not bioaccumulate and do not appear to be subject to biomagnification as a result of trophic transfer through food webs, with >99% of observations from field-based studies reporting MPs to be located within the gastrointestinal tract. Overall, there is substantial heterogeneity in how samples are collected, processed, analyzed, and reported, causing significant challenges in attempting to assess temporal and spatial trends or in helping to inform mechanistic understanding. Nevertheless, several studies suggest that the characteristics of MPs ingested by organisms is generally representative of plastic debris in the vicinity of where individuals are collected. Monitoring spatial and temporal trends of ingested MPs could thus potentially be useful in assessing mitigation efforts aimed at reducing the emission of plastic and MPs to the environment. The development and application of standardized analytical methods are urgently needed to better understand spatial and temporal trends. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND Organoids provide a powerful system to study epithelia in vitro. Recently, this approach was applied successfully to the biliary tree, a series of ductular tissues responsible for the drainage of bile and pancreatic secretions. More precisely, organoids have been derived from ductal tissue located outside (Extrahepatic Bile Ducts or EHBDs) or inside the liver (Intrahepatic bile ducts or IHBDs). These organoids share many characteristics including the expression of cholangiocyte markers such as KRT19. However, the relationship between these organoids and their tissues of origin, and to each other, is largely unknown. U18666A molecular weight METHODS/RESULTS Organoids were derived from human gallbladder, common bile duct, pancreatic duct and intrahepatic bile ducts using culture conditions promoting WNT signaling. The resulting IHBD and EHBD organoids expressed stem/progenitor markers LGR5/PROM1 and ductal markers KRT19/KRT7. However, RNA-sequencing revealed that organoids conserve only a limited number of regional-specific markers corresponding to their location of origin. Of particular interest, downregulation of biliary markers and upregulation of cell cycle genes was observed in organoids. IHBD and EHBD organoids diverged in their response to WNT signaling and only IHBD were able to express a low-level of hepatocyte markers under differentiation conditions. CONCLUSIONS Taken together, our results demonstrate that differences exist not only between extrahepatic biliary organoids and their tissue of origin but also between IHBD and EHBD organoids. This information may help to understand the tissue specificity of cholangiopathies and also to identify new targets for therapeutic development. This article is protected by copyright. All rights reserved.The current study pertains to a POCIS laboratory calibration to estimate the sampling rates (Rs) for 44 pharmaceuticals featuring a wide range of polarity (-0.6 less then logKow less then 5.4). The calibration was performed at 16.0° ± 1.5°C for 4 water flow velocities (0, 2-3, 6-7 and 20 cm/s) in both a tank (for calibration at 0 cm/s) and a laboratory-scale artificial river filled with 200 and 500 L of tap water spiked with 0.3 µg/L of each compound, respectively. Twelve new Rs and 26 Rs already available in the literature were determined, whereas the sampling rates for 6 pharmaceuticals could not be determined due to nonlinearity or poor accumulation in POCIS. An increase in the Rs value with flow velocity was observed, which is consistent with a decrease in the effective thickness of the water boundary layer at the POCIS membrane surface. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Little is known about the role of low-carbohydrate diets (LCDs) in the development of hepatocellular carcinoma (HCC). We prospectively evaluated the associations between plant-based and animal-based LCDs and risk of HCC in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Dietary intake was assessed every 4 years using validated food frequency questionnaires. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). HRs are shown for a 1-standard deviation (SD) increment with variable modelled as continuous. During 3,664,769 person years of follow-up, there were 156 incident HCC cases. Although there were no associations between overall or animal-based LCD score and risk of HCC, plant-based LCD score was inversely associated with HCC risk (HR 0.83; 95% CI 0.70-0.98; Ptrend =0.03). Carbohydrate intake, especially from refined grains (HR 1.18; 95% CI 1.00-1.39; Ptrend =0.04) was positively, while plant fat (HR 0.78; 95% CI 0.65-0.95; Ptrend =0.01) was inversely associated with HCC risk. Substituting 5% of energy from plant fat and protein for carbohydrate (HR 0.74; 95% CI 0.58-0.93; Ptrend =0.01) or refined grains (HR 0.70; 95% CI 0.55-0.90; Ptrend =0.006) was associated with lower HCC risk. In conclusion, a plant-based LCD and dietary restriction of carbohydrate from refined grains were associated with a lower risk of HCC. Substituting plant fat and protein for carbohydrate, particularly refined grains, may decrease HCC incidence. Our findings support a potential benefit in emphasizing plant sources of fat and protein in the diet for HCC primary prevention. Additional studies that carefully consider hepatitis B and C virus infections and chronic liver diseases are needed to confirm our findings. This article is protected by copyright. All rights reserved.

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