Choline, an essential dietary nutrient for humans, is required for the synthesis of the neurotransmitter, acetylcholine, the methyl group donor, betaine, and phospholipids; and therefore, choline is ...involved in a broad range of critical physiological functions across all stages of the life cycle. The current dietary recommendations for choline have been established as Adequate Intakes (AIs) for total choline; however, dietary choline is present in multiple different forms that are both water-soluble (e.g., free choline, phosphocholine, and glycerophosphocholine) and lipid-soluble (e.g., phosphatidylcholine and sphingomyelin). Interestingly, the different dietary choline forms consumed during infancy differ from those in adulthood. This can be explained by the primary food source, where the majority of choline present in human milk is in the water-soluble form, versus lipid-soluble forms for foods consumed later on. This review summarizes the current knowledge on dietary recommendations and assessment methods, and dietary choline intake from food sources across the life cycle.
Small noncoding microRNAs act as post-transcriptional regulators of gene expression involved in diverse biologic functions. Pregnane X receptor (PXR, NR1I2), a member of the superfamily of nuclear ...receptors, is a transcription factor governing the transport and biotransformation of various drugs and other chemicals. In the present study, we identified a specific microRNA (miR) involved in regulating the expression and functionality of human PXR (hPXR). According to bioinformatics analysis employing three commonly used algorithms (TargetScan, miRanda, and DIANA-microT-CDS), miR-18a-5p was predicted to be the top candidate microRNA regulator of hPXR. Consequently, this microRNA was selected for detailed experimental investigation. As shown in cell-based dual-luciferase reporter gene assays, functional interaction occurred between miR-18a-5p and the microRNA recognition element of miR-18a-5p in the 3'-untranslated region of hPXR mRNA. Transfection of LS180 human colorectal adenocarcinoma cells with an miR-18a-5p mimic decreased hPXR mRNA and protein expression, whereas transfection of LS180 cells with an miR-18a-5p inhibitor increased hPXR mRNA and protein expression. The decrease in hPXR expression by the miR-18a-5p mimic was associated with a reduction in the extent of hPXR target gene (
) induction by rifampin and rilpivirine. Treatment of untransfected LS180 cells with either of these hPXR agonists decreased endogenous expression of miR-18a-5p, and this preceded the onset of
induction. In conclusion, miR-18a-5p is a negative regulator of hPXR expression and the hPXR agonists rifampin and rilpivirine are chemical suppressors of miR-18a-5p expression.
Plasma concentrations of choline and its metabolites might serve as biomarkers for the health outcomes of several pathological states such as cardiovascular disease and cancer. However, information ...about the reliability of biomarkers of choline status is limited. We investigated biological variations in repeated measures of choline and metabolites in healthy adults to assess them as biomarkers.
Blood samples were collected after an overnight fast at three-time points 12 days apart from 40 adults (mean age, 33 y; male, n = 21). A subset (n = 19; male, n = 8) provided one additional sample after a breakfast meal. Plasma free choline, betaine and dimethylglycine were measured using liquid chromatography-tandem mass spectrometry, and plasma phosphatidylcholine, sphingomyelin and lysophosphatidylcholine were measured using high-performance liquid chromatography.
The biological variations observed for choline and metabolites were ≤ 13% for adult fasting samples. This corresponded to intra-class correlations (ICC) that ranged from 0.593 to 0.770 for fasting values for choline and metabolites. A similar ICC range was also obtained between fasting and post-prandial states. Although most post-prandial concentrations of choline and metabolites were significantly higher (P < .05) than fasting, all fell within a calculated reference interval. The participants were correctly classified in tertiles for fasting and post-prandial states for choline (68%) and metabolites (range = 32% phosphatidylcholine and 79% for sphingomyelin).
These findings indicate that biological variations of choline and metabolites are low in healthy adults and values from a single blood sample can be used as a biomarker. However, choosing phosphatidylcholine as a biomarker is less reliable.
•Biomarkers of choline status were assessed in fasting and post-prandial subjects.•Biomarkers had low biological variations and high reliability in fasting subjects.•Most biomarkers correctly identified ranking in fasting and post-prandial states.•A single blood sample can be used to quantitate choline and most of its metabolites.•Using a single sample to assess phosphatidylcholine was less reliable.
The national Air Pollution Prevention and Control Action Plan required significant decreases in PM_（2.5） levels over China.To explore more effective emission abatement strategies in industrial ...cities,a case study was conducted in Baotou to evaluate the current national control measures.The total emissions of SO_2,NO_X,PM_（2.5） and NMVOC（non-methane volatile organic compounds） in Baotou were 211.2 Gg,156.1 Gg,28.8 Gg,and 48.5 Gg,respectively in 2013,and they would experience a reduction of 30.4%,26.6%,15.1%,and 8.7%,respectively in 2017 and 39.0%,32.0%,24.4%,and 12.9%,respectively in2020.The SO_2,NO_Xand PM_（2.5） emissions from the industrial sector would experience a greater decrease,with reductions of 37%,32.7 and 24.3%,respectively.From 2013 to 2020,the concentrations of SO_2,NO_2,and PM_（2.5） are expected to decline by approximately 30%,10% and 14.5%,respectively.The reduction rate of SNA（sulfate,nitrate and ammonium）concentrations was significantly higher than that of PM_（2.5） in 2017,implying that the current key strategy toward controlling air pollutants from the industrial sector is more powerful for SNA.Although air pollution control measures implemented in the industrial sector could greatly reduce total emissions,constraining the emissions from lower sources such as residential coal combustion would be more effective in decreasing the concentration of PM_（2.5） from 2017 to 2020.These results suggest that even for a typical industrial city,the reduction of PM_（2.5） concentrations not only requires decreases in emissions from the industrial sector,but also from the low emission sources.The seasonal variation in sulfate concentration also showed that emission from coal-burning is the key factor to control during the heating season.
Choline has critical roles during periods of rapid growth and development, such as infancy. In human milk, choline is mostly present in water-soluble forms (free choline, phosphocholine, and ...glycerophosphocholine). It is thought that milk choline concentration is influenced by maternal choline intake, and the richest food sources for choline are of animal origin. Scarce information exists on milk choline from countries differing in animal-source food availability. In this secondary analysis of samples from previous trials, the concentrations of the water-soluble forms of choline were quantified by liquid chromatography-tandem mass spectrometry in mature milk samples collected from lactating women in Canada (
= 301) and in Cambodia (
= 67). None of the water-soluble forms of choline concentrations in milk differed between Canada and Cambodia. For all milk samples (
= 368), free choline, phosphocholine, glycerophosphocholine, and the sum of water-soluble forms of choline concentrations in milk were (mean (95%CI)) 151 (141, 160, 540 (519, 562), 411 (396, 427), and 1102 (1072, 1133) µmol/L, respectively. Theoretically, only 19% of infants would meet the current Adequate Intake (AI) for choline. Our findings suggest that the concentrations in milk of water-soluble forms of choline are similar in Canada and Cambodia, and that the concentration used to set the infant AI might be inaccurate.
•A direct two-way coupling of hydrologic and 1D-2D hydrodynamic models is proposed.•The refined river links are used to couple hydrologic and 1D hydrodynamic models.•The proposed model allows runoff ...discharge into 2D inundation areas and 1D rivers.•The model demonstrates superior physical representation of the flood process.
A direct two-way coupling of hydrologic and 1D-2D hydrodynamic models (DCM2D) for watershed flood simulation was proposed. This coupling included three models (i.e., fully distributed hydrologic, 1D hydrodynamic, and 2D hydrodynamic models) and three coupling strategies: the bidirectionally coupled hydrologic-2D hydrodynamic module, two-way coupled hydrologic-1D hydrodynamic module (HH1D), and two-way coupled 1D-2D hydrodynamic module (HH2D). The refined river links (RLs) were used to couple the hydrologic and 1D hydrodynamic models, and the exchange discharge between these models was determined using either the weir flow equations or hydrologic model, depending on the flow transitions. Four cases were used to evaluate the proposed DCM2D. The results indicated that the discharge obtained from the proposed HH1D exhibited a high level of consistency with analytical solutions, with NSE of 0.986. This finding supported the validity of the proposed coupling schemes for hydrologic and 1D hydrodynamic models, particularly in scenarios where there were no distinct flow transitions. The DCM2D accurately represented the physical flood process by allowing rainfall runoff discharge into both 2D low-lying inundation regions and 1D rivers. This contrasted with the indirect coupling models (ICM2D), which required runoff to enter the 1D rivers before flowing into the 2D inundation regions. It exhibited reasonable flow directions and achieved satisfactory simulation accuracy, with higher NSE compared to the ICM2D. The proposed DCM2D model can effectively adapt to the real-life flood evolution process and offer practical and reliable solutions for simulating floods in watersheds.
Platelet-derived growth factor (PDGF)-, epidermal growth factor (EGF)- and insulin-like growth factor I (IGF-I)-stimulated cell proliferation in 3T3 cells was accompanied by increased abundance of ...labile intracellular pool of zinc (LIPZ). However, the origin and regulation of this cell proliferation-associated increase in the abundance of LIPZ are unknown. Cellular zinc homeostasis involves zinc transporters and metallothionein. The objectives of this study were to determine whether cell proliferation-associated increase in the abundance of LIPZ was a result of an increased zinc uptake and to assess the involvement of zinc transporters and metallothionein in this cell proliferation-associated increase in the abundance of LIPZ in 3T3 fibroblasts. Zinc transporters assessed included both zinc importer (Zip1) and zinc exporters (ZnT1, ZnT2 and ZnT4). Growth factors increased the abundance of LIPZ while total cellular zinc concentration remained unaffected, demonstrating that LIPZ was responsive to the increased needs for zinc during growth factor-stimulated cell proliferation. Growth factors also increased net zinc retention as indicated by higher
65zinc radioactivity and elevated mRNA levels of Zip1, ZnT1 and ZnT4. Although zinc is essential to cell proliferation, excessive cellular zinc accumulation causes cytotoxicity. Collectively, these observations suggest that increase in the abundance of LIPZ during growth factor-stimulated cell proliferation was due to increased net retention of extracellular zinc, which was apparently achieved through a coordinated up-regulation of the expression of transporters involved in both zinc influx and efflux to ensure adequate supply of zinc to sustain cell proliferation, yet to prevent potential zinc cytotoxicity in 3T3 cells.
Abstract only
We have previously shown that zinc depletion induces apoptosis in MDA‐MB‐231 cells. Ca
2+
is a known mediator of apoptosis. The objective of this study was to establish the role of ...intracellular Ca
2+
in zinc depletion‐induced apoptosis in MDA‐MB‐231 cells. After cultured in DMEM+10% FBS for 3 days, the cells were treated with N,N,N′,N′‐tetrakis2‐pyridylmethylethylenediamine (TPEN; 20μM) alone for 0–72h or in the presence of 1,2‐bis(2‐ aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid acetoxymethyl ester (BAPTA; 0–40μM) for 6 or 72h. Intracellular Ca
2+
was assessed by Fura2 assay. Apoptosis was assessed by caspase‐3 activity and propidium iodide flow cytometric assay. To affirm that TPEN‐induced apoptosis was zinc specific, zinc (0–40μM; 72h) was replenished in the presence of TPEN. TPEN induced a treatment duration‐dependent elevation of intracellular Ca
2+
level, caspase‐3 activity, and proportion of apoptotic cells. Zinc replenishment suppressed TPEN‐induced apoptosis. TPEN and BAPTA co‐treatments suppressed TPEN‐induced apoptosis in a dose‐dependent manner. These results suggested that intracellular Ca
2+
served as a mediator in zinc depletion‐induced apoptosis in MDA‐MB‐231 cells.
Supported by NSERC.
Abstract only
We have previously shown that zinc depletion induces a Ca
2+
‐ dependent apoptosis in MDA‐MB‐231 cells. This zinc depletioninduced apoptosis is associated with an increased Bax:Bcl‐2 ...ratio and an elevated caspase‐9 and −3 activities while caspase‐8 activity remains unchanged. We hypothesized that Ca
2+
‐dependent depolarization of the mitochondrial membrane is involved in zinc depletion‐induced apoptosis. To test this hypothesis, MDA‐MB‐ 231 cells were cultured in DMEM+10% FBS for 3 days followed by treating the cells with N,N,N′,N′‐tetrakis2‐ pyridylmethylethylenediamine (TPEN; 20μM) alone for 0–24h or in the presence of 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid acetoxymethyl ester (BAPTA; 0–20μM) for 24h. Mitochondrial membrane potential was assessed by a DiOC
6
flow cytometric assay. TPEN caused depolarization of the mitochondrial membrane in a treatment duration‐dependent manner (2–24h; R
2
=0.99). BAPTA reduced TPEN‐induced depolarization of the mitochondrial membrane by 62–79%. Collectively, these results indicated that zinc depletion‐induced apoptosis was mediated through a Ca
2+
‐dependent depolarization of the mitochondrial membrane in MDA‐MB‐231 cells.
Supported by NSERC.
In order to mitigate the flood disaster, an integrated structural flood control system, mainly incorporating levees, reservoirs, and flood diversion and detention zones, has been established in the ...JingJiang Reach of the Yangtze River by the efforts of Chinese government after several decades. The flood control effect of the integrated structural flood control system on mitigating the most catastrophic flood in history record which did occur in 1870 was assessed. According to the results, the used storage for flood control of the Three Gorges Reservoir is 18.4 billion m3 and the used storage for flood control of the other upstream reservoirs is 9.3 billion m3. The used flood storage of the Jingjiang Flood Diversion Zone is 5.4 billion m3 and the highest water level at Shashi Station is 45.00m. It shows that the flood control safety in the Jingjiang Reach is ensured to reach the achievement that controlling the highest water level at Shashi Station no more than 45.00m in the flood of 1870 to avoid the likely catastrophic flood disaster in the Jianghan plain and Dongting Lake plain along the Jingjiang Reach.
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