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Supplementary materials, methods and figures

De novo nucleotide biosynthesis is essential for maintaining cellular nucleotide pools, the suppression of which leads to genome instability. The metabolic enzyme transketolase (TKT) in the nonoxidative branch of the pentose phosphate pathway (PPP) regulates ribose 5-phosphate (R5P) levels and de novo nucleotide biosynthesis. TKT is required for maintaining cell proliferation in human liver cancer cell lines, yet the role of TKT in liver injury and cancer initiation remains to be elucidated. In this study, we generated a liver-specific TKT knockout mouse strain by crossing TKTflox/flox mice with albumin-Cre mice. Loss of TKT in hepatocytes protected the liver from diethylnitrosamine (DEN)-induced DNA damage without altering DEN metabolism. DEN treatment of TKT-null liver increased levels of R5P and promoted de novo nucleotide synthesis. More importantly, supplementation of dNTPs in primary hepatocytes alleviated DEN-induced DNA damage, cell death, inflammatory response, and cell proliferation. Furthermore, DEN and high-fat diet (HFD)–induced liver carcinogenesis was reduced in TKTflox/floxAlb-Cre mice compared with control littermates. Mechanistically, loss of TKT in the liver increased apoptosis, reduced cell proliferation, decreased TNFα, IL6, and STAT3 levels, and alleviated DEN/HFD-induced hepatic steatosis and fibrosis. Together, our data identify a key role for TKT in promoting genome instability during liver injury and tumor initiation.Significance:These findings identify transketolase as a novel metabolic target to maintain genome stability and reduce liver carcinogenesis.

Inflammatory bowel disease (IBD) has a close association with transketolase (TKT) that links glycolysis and the pentose phosphate pathway (PPP). However, how TKT functions in the intestinal epithelium remains to be elucidated. To address this question, we specifically delete TKT in intestinal epithelial cells (IECs). IEC TKT-deficient mice are growth retarded and suffer from spontaneous colitis. TKT ablation brings about striking alterations of the intestine, including extensive mucosal erosion, aberrant tight junctions, impaired barrier function, and increased inflammatory cell infiltration. Mechanistically, TKT deficiency significantly accumulates PPP metabolites and decreases glycolytic metabolites, thereby reducing ATP production, which results in excessive apoptosis and defective intestinal barrier. Therefore, our data demonstrate that TKT serves as an essential guardian of intestinal integrity and barrier function as well as a potential therapeutic target for intestinal disorders.

Deregulated metabolism is one of the characteristics of hepatocellular carcinoma. Sex hormone receptor signalling has been involved in the marked gender dimorphism of hepatocellular carcinoma pathogenesis. Oestrogen receptor (ER) has been reported to reduce the incidence of liver cancer. However, it remains unclear how oestrogen and ER regulate metabolic alterations in liver tumour cells. Our previous work revealed that ERα interacted with carbohydrate responsive element binding protein (ChREBP), which is a transcription factor promoting aerobic glycolysis and proliferation of hepatoma cells. Here, the data showed that ERα overexpression with E2 treatment reduced aerobic glycolysis and cell proliferation of hepatoma cells. In addition to modestly down‐regulating ChREBP transcription, ERα promoted ChREBP degradation. ERα co‐immunoprecipitated with both ChREBP‐α and ChREBP‐β, the two known subtypes of ChREBP. Although E2 promoted ERα to translocate to the nucleus, it did not change subcellular localization of ChREBP. In addition to interacting with ChREBP‐β and promoting its degradation, ERα decreased ChREBP‐α–induced ChREBP‐β transcription. Taken together, we confirmed an original role of ERα in suppressing aerobic glycolysis in liver cancer cells and elucidated the mechanism by which ERα and ChREBP‐α together regulated ChREBP‐β expression.

Objective: The objective of this study was to determine net energy (NE) of expeller-press (EP-RSM) and solvent-extracted rapeseed meal (SE-RSM) and to establish equations for predicting the NE in rapeseed meal (RSM) fed to growing pigs.Methods: Thirty-six barrows (initial body weight [BW], 41.1±2.2 kg) were allotted into 6 diets comprising a corn-soybean meal basal diet and 5 diets containing 19.50% RSM added at the expense of corn and soybean meal. The experiment had 6 periods and 6 replicate pigs per diet. During each period, the pigs were individually housed in metabolism crates for 16 days which included 7 days for adaption to diets. On day 8, pigs were transferred to respiration chambers and fed their respective diet at 2,000 kJ metabolizable energy (ME)/kg BW0.6/d. Feces and urine were collected, and daily heat production was measured from day 9 to 13. On days 14 and 15, the pigs were fed at 890 kJ ME/kg BW0.6/d and fasted on day 16 for evaluation of fasting heat production (FHP).Results: The FHP of pigs averaged 790 kJ/kg BW0.6/d and was not affected by the diet composition. The NE values were 10.80 and 8.45 MJ/kg DM for EP-RSM and SE-RSM, respectively. The NE value was positively correlated with gross energy (GE), digestible energy (DE), ME, and ether extract (EE). The best fit equation for NE of RSM was NE (MJ/kg DM) = 1.14×DE (MJ/kg DM)+0.46×crude protein (% of DM)–25.24 (n = 8, R2 = 0.96, p2 = 0.77, p = 0.018) may be utilized to quickly determine the NE in RSM when DE or ME values are unavailable.Conclusion: The NE values of EP-RSM and SE-RSM were 10.80 and 8.45 MJ/kg DM. The NE value of RSM can be well predicted based on energy content (GE, DE, and ME) and proximate analysis.

Obesity has recently become a prevalent health threat worldwide. Although emerging evidence has suggested a strong link between the pentose phosphate pathway (PPP) and obesity, the role of transketolase (TKT), an enzyme in the nonoxidative branch of the PPP that connects PPP and glycolysis, remains obscure in adipose tissues. In this study, we specifically deleted TKT in mouse adipocytes and found no obvious phenotype upon normal diet feeding. However, adipocyte TKT abrogation attenuated high-fat diet–induced obesity, reduced hepatic steatosis, improved glucose tolerance, alleviated insulin resistance, and increased energy expenditure. Mechanistically, TKT deficiency accumulated nonoxidative PPP metabolites and decreased glycolysis and pyruvate input into the mitochondria, leading to increased lipolytic enzyme gene expression and enhanced lipolysis, fatty acid oxidation, and mitochondrial respiration. Therefore, our data not only identify a novel role of TKT in regulating lipolysis and obesity but also suggest that limiting glucose-derived carbon into the mitochondria induces lipid catabolism and energy expenditure.

This study was conducted to determine the digestible energy (DE) and metabolizable energy (ME) values and apparent total tract digestibility (ATTD) of nutrients in four fibrous ingredients [corn distillers’ dried grains with solubles (DDGS), soybean hull, wheat bran, and corn bran] fed to barrows at three different growth stages. Thirty growing barrows, 30 finishing barrows, and 30 fattening barrows (initial body weights of 29.04, 58.57, and 105.65 kg, respectively) were individually housed in metabolism crates and allotted to one of four test diets or a basal corn–soybean meal diet in a 3 × 5 factorial design. Fecal and urine samples were collected for 5 d after a 12 d adaption period. The DE and ME values and ATTD of gross energy (GE), organic matter (OM), crude protein, and acid detergent fiber (ADF) in wheat bran, as well as the ATTD of GE, OM, neutral detergent fiber (NDF), and ADF in corn DDGS, and ATTD of NDF and ADF in soybean hull, were greater (P

This study was conducted to determine the effect of different growing stages on digestible energy (DE) and metabolizable energy (ME) in soybean meal (SBM), cottonseed meal (CSM), rapeseed meal (RSM), corn gluten meal (CGM), and corn distillers dried grains with solubles (DDGS) fed to crossbred barrows. Thirty-six growing barrows (GS 1: 29.1 ± 2.85 kg BW), 36 growing barrows (GS 2: 59.2 ± 4.91 kg BW), and 36 finishing barrows (GS 2: 105.4 ± 6.91 kg BW) were allotted to 6 diets in a completely randomized design with 6 replicated pigs per diet per growth stage or BW. Faecal and urine samples were collected for 5 days after a 12-day adaption period. The results showed that the concentration of DE in corn for pigs at GS 3 was greater (P

Obesity has recently become a prevalent health threat worldwide. Although emerging evidence has suggested a strong link between the pentose phosphate pathway (PPP) and obesity, the role of transketolase (TKT), an enzyme in the non-oxidative branch of the PPP which connects PPP and glycolysis, remains obscure in adipose tissues. In this study, we specifically delete TKT in mouse adipocytes and find no obvious phenotype upon normal diet feeding. However, adipocyte TKT abrogation attenuates high fat diet (HFD)-induced obesity, reduces hepatic steatosis, improves glucose tolerance, alleviates insulin resistance and increases energy expenditure. Mechanistically, TKT deficiency accumulates non-oxidative PPP metabolites, decreases glycolysis and pyruvate input into the mitochondria, leading to increased lipolytic enzyme gene expression and enhanced lipolysis, fatty acid oxidation and mitochondrial respiration. Therefore, our data not only identify a novel role of TKT in regulating lipolysis and obesity, but also suggest limiting glucose-derived carbon into the mitochondria induces lipid catabolism and energy expenditure.

This study was conducted to determine the optimal adaptation duration of growing pigs to high fiber diets for net energy (NE) determination and the effect of soluble and insoluble fiber on nutrient digestibility and energy metabolism using indirect calorimetry. Eighteen growing barrows (initial BW: 36.1 ± 3.1 kg) were allotted in a completely randomized design to 3 dietary treatments. The 3 experimental diets included a corn-soybean meal basal diet and 2 test diets formulated to contain either 220 g/kg sugar beet pulp or 200 g/kg soybean hulls at the expense of corn, soybean meal and amino acid (AA) in the basal diet. The experiment was conducted in 3 consecutive 28-d periods consisting of a 7-d preliminary period followed by a 21-d heat production (HP) measurement period, and the HP measurement period was artificially divided into 4 adaptation duration (collection periods) of 5 d (from d 8 to d 12, d 13 to d 17, d 18 to d 22, d 23 to d 27) in order to calculate DE, ME and NE values and digestibility coefficients of nutrients within each collection period and pig. Pigs required to be adapted to the three diets for these many days before they could finish the daily feed allowance. Indeed, pigs needed 7, 12 and 10 days finishing eating the basal, sugar beet pulp and soybean hulls diet, respectively. The coefficient of apparent total tract digestibility (CATTD) of dry matter (DM), total dietary fiber (TDF), neutral detergent fiber assayed with a heat stable amylase and expressed inclusive of residual ash (aNDF), ether extract (EE) and organic matter (OM) were not significantly changed with adaptation duration for respective diets. Nitrogen retention was increased (P

The present study was conducted to investigate the effects of feeding level and dietary supplementation with crystalline amino acids (AA) on the determination of energy contents in corn for growing pigs. A total of 36 barrows with an average initial body weight of 41.4 ± 2.0 kg were allocated across six treatments in a 2 × 3 factorial arrangement that included 2 feeding levels (2400 kJ ME/kg BW0.6 per day or ad libitum) and 3 dietary AA supplementation patterns (corn diet with no AA; corn + 3AA diet with addition of lysine, threonine and tryptophan; corn + 5AA diet with greater levels of crystalline lysine, threonine and tryptophan supplementation than those in corn + 3AA diet plus crystalline methionine and isoleucine supplementation). The experiment was conducted in 6 consecutive periods. During each period, 6 pigs were allotted to 1 of 6 treatments, and each treatment corresponded to 1 of 6 respiration chambers. In each period, pigs were individually housed in metabolism crates and fed their respective diets at two feeding levels for 13 d, including 7 d adaptation to the feed, metabolism crate and environmental conditions. On d 8, the pigs were transferred to respiration chambers. Total feces and urine samples were collected and heat production was measured from d 8 to 12. On the last day of each period, the pigs were fasted for 24 h and fasting heat production was subsequently measured. The apparent total tract digestibility (ATTD) of dry matter (DM), organic matter (OM) and gross energy (GE) in diets and corn were not affected by feeding level; however, increasing feeding level tended (P = 0.09) to decrease the ATTD of crude protein (CP). Nitrogen retention increased (P

The objective of this experiment was to determine the effects of increased fiber content in diets on heat production (HP) and NE:ME ratio and to determine the NE content and NE:ME ratio of full-fat rice bran (FFRB), defatted rice bran (DFRB), corn gluten feed (CGF), and corn germ meal (CGM) fed to growing barrows using indirect calorimetry (IC). Thirty growing barrows (28.5 ± 2.4 kg BW) were allotted in a completely randomized design to 5 dietary treatments that included a corn–soybean meal basal diet and 4 experimental diets with a constant ratio of corn and soybean meal (difference method) containing 30% FFRB, DFRB, CGF, and CGF. Pigs were housed in individual metabolism crates for 20 d including 14-d adaptation to the diet and 6 d to determine the HP and total collection of feces and urine in respiration chambers. Pigs were fed their respective diets at 550 kcal ME·kg BW(0.60−1)·d(−1) on the basis of BW measured on days 0, 7, and 14. The apparent total tract digestibility (ATTD) of DM, GE, and OM were greater (P < 0.01) in pigs fed the basal diet. The ATTD of DM, GE, and OM in pigs fed the DFRB diet were lesser (P < 0.01) when compared with those fed the basal and FFRB diets. The ATTD of ether extract (EE) in pigs fed the FFRB diet was greater (P < 0.01) compared with those fed basal, DFRB, CGF, and CGM diets. The HP adjusted for the same ME intake was greater (P < 0.01) in pigs fed the DFRB, CGF, and CGM diets compared with those fed basal and FFRB diets. The NE:ME ratio in pigs fed the FFRB diet was greater (P < 0.01) when compared with those fed the DFRB, CGF, and CGM diets. The NE content of FFRB, DFRB, CGF, and CGM determined using the IC method were 2,952, 1,100, 1,747, and 2,079 kcal/kg DM, respectively. The NE content of FFRB, CGF, and CGM determined using the IC method were 3.5%, 3.8%, and 1.8% greater, respectively, than the predicted values, whereas NE content of DFRB determined using the IC method was 2.1% lower than the predicted values. In conclusion, pigs fed the fiber-rich ingredients had greater HP and lower nutrient digestibility. However, pigs fed FFRB diets containing greater fat content had a lower heat increment and, therefore, higher utilization efficiency. The NE:ME ratio ranged from 71.6% to 82.4%. The NE of FFRB, DFRB, CGF, and CGM determined using the IC method were 2,952, 1,100, 1,747, and 2,079 kcal/kg DM, respectively.

The objective of this experiment was to determine the NE content of different dietary lipids fed to growing pigs using indirect calorimetry. Thirty-six growing (initial BW: 41.1 ± 3.1 kg) barrows were allotted to 6 diets based on completely randomized design with 6 replicate pigs per diet. Diets included a corn-soybean meal basal diet and 5 test diets each containing 10% palm oil, poultry fat, fish oil, corn oil, or flaxseed oil at the expense of corn and soybean meal. During each period, pigs were individually housed in metabolism crates for 14 d, which included 7 d for adaptation to feed, metabolism crates, and environmental conditions. On day 8, pigs were transferred to the open-circuit respiration chambers and fed 1 of the 6 diets at 2.3 MJ ME/kg BW0.6/day. Total feces and urine were collected and daily heat production (HP) was also calculated from day 9 to day 13. On the last day of each period (day 14), pigs were fasted and the fasting heat production (FHP) was measured. The results show that the FHP of pigs averaged 809 kJ/kg BW0.6·day-1 and was not affected by diet characteristics. The DE values were 35.98, 36.84, 37.11, 38.95, and 38.38 MJ/kg DM, the ME values were 35.79, 36.56, 36.92, 37.73, and 38.11 MJ/kg DM, and the NE values were 32.42, 33.21, 33.77, 34.00, and 34.12 MJ/kg DM, for the palm oil, poultry fat, fish oil, corn oil, and flaxseed oil, respectively. Based on our result, we concluded that the DE content of dietary lipid varied from 91% to 98% of its GE content, the ME content of dietary lipid was approximately 99% of its DE content, and the NE content of dietary lipid was approximately 90% of its ME content in growing pigs.

Background & Aims The metabolic features and function of intratumoral regulatory T cells (Tregs) are ambiguous in colorectal cancer. Tumor-infiltrating Tregs are reprogrammed to exhibit high glucose-depleting properties and adapt to the glucose-restricted microenvironment. The glucose-responsive transcription factor MondoA is highly expressed in Tregs. However, the role of MondoA in colorectal cancer-infiltrating Tregs in response to glucose limitation remains to be elucidated. Methods We performed studies using mice, in which MondoA was conditionally deleted in Tregs, and human colorectal cancer tissues. Seahorse and other metabolic assays were used to assess Treg metabolism. To study the role of Tregs in antitumor immunity, we used a subcutaneous MC38 colorectal cancer model and induced colitis-associated colorectal cancer in mice by azoxymethane and dextran sodium sulfate. Results Our analysis of single-cell RNA sequencing data of patients with colorectal cancer revealed that intratumoral Tregs featured low activity of the MondoA–thioredoxin-interacting protein (TXNIP) axis and increased glucose uptake. Although MondoA-deficient Tregs were less immune suppressive and selectively promoted T-helper (Th) cell type 1 (Th1) responses in a subcutaneous MC38 tumor model, Treg-specific MondoA knockout mice were more susceptible to azoxymethane-DSS–induced colorectal cancer. Mechanistically, suppression of the MondoA-TXNIP axis promoted glucose uptake and glycolysis, induced hyperglycolytic Th17-like Tregs, which facilitated Th17 inflammation, promoted interleukin 17A-induced of CD8+ T-cell exhaustion, and drove colorectal carcinogenesis. Blockade of interleukin 17A reduced tumor progression and minimized the susceptibility of MondoA-deficient mice to colorectal carcinogenesis. Conclusions The MondoA-TXNIP axis is a critical metabolic regulator of Treg identity and function in the colorectal cancer microenvironment and a promising target for cancer therapy.

This study was conducted to determine the digestible (DE) and metabolisable energy (ME) content and the coefficient of apparent total tract digestibility (CATTD) of gross energy (GE) in 4 cereal grains (corn, wheat, barley and sorghum) fed to barrows and to quantify the effect of body weight (BW) on the digestibility of the 4 cereal grains. Twenty-four weanling barrows (13.3 ± 0.8 BW, stage 1), 24 growing barrows (31.6 ± 1.5 BW, stage 2), 24 finishing barrows (56.7 ± 1.8 BW, stage 3) and 24 fattening barrows (111 ± 3.8 BW, stage 4) were individually housed in metabolic crates and allotted to 1 of 4 diets with 6 pigs fed each diet at each BW in a completely randomized design. The 4 diets consisted of 973.4 g/kg of a cereal grain and 26.6 g/kg of vitamins and minerals. Faeces and urine samples were collected for 5 d following a 10 d adaptation period. The DE and ME content and the CATTD of GE in corn and wheat were greater (P

The glucose-responsive transcription factor carbohydrate response element–binding protein (ChREBP) critically promotes aerobic glycolysis and cell proliferation in colorectal cancer cells. It has been reported that ubiquitination may be important in the regulation of ChREBP protein levels and activities. However, the ChREBP-specific E3 ligase and molecular mechanism of ChREBP ubiquitination remains unclear. Using database exploration and expression analysis, we found here that levels of the E3 ligase SMURF2 (Smad-ubiquitination regulatory factor 2) negatively correlate with those of ChREBP in cancer tissues and cell lines. We observed that SMURF2 interacts with ChREBP and promotes ChREBP ubiquitination and degradation via the proteasome pathway. Interestingly, ectopic SMURF2 expression not only decreased ChREBP levels but also reduced aerobic glycolysis, increased oxygen consumption, and decreased cell proliferation in colorectal cancer cells. Moreover, SMURF2 knockdown increased aerobic glycolysis, decreased oxygen consumption, and enhanced cell proliferation in these cells, mostly because of increased ChREBP accumulation. Furthermore, we identified Ser/Thr kinase AKT as an upstream suppressor of SMURF2 that protects ChREBP from ubiquitin-mediated degradation. Taken together, our results indicate that SMURF2 reduces aerobic glycolysis and cell proliferation by promoting ChREBP ubiquitination and degradation via the proteasome pathway in colorectal cancer cells. We conclude that the SMURF2–ChREBP interaction might represent a potential target for managing colorectal cancer.

Objective: Feed energy required for pigs is first prioritized to meet maintenance costs. Additional energy intake in excess of the energy requirement for maintenance is retained as protein and fat in the body, leading to weight gain. The objective of this study was to estimate the metabolizable energy requirements for maintenance (MEm) by regressing body weight (BW) gain against metabolizable energy intake (MEI) in growing pigs.[br/] Methods: Thirty-six growing pigs (26.3 +/- 1.7 kg) were allotted to 1 of 6 treatments with 6 replicates per treatment in a randomized complete block design. Treatments were 6 feeding levels which were calculated as 50%, 60%, 70%, 80%, 90%, or 100% of the estimated ad libitum MEI (2,400 kJ/kg BW0.60 d). All pigs were individually housed in metabolism crates for 30 d and weighed every 5 d. Moreover, each pig from each treatment was placed in the open-circuit respiration chambers to measure heat production (HP) and energy retained as protein (REp) and fat (REf) every 5 d. Serum biochemical parameters of pigs were analyzed at the end of the experiment.[br/] Results: The average daily gain (ADG) and HP as well as the REp and REf linearly increased with increasing feed intake (p< 0.010). beta-hydroxybutyrate concentration of serum tended to increase with increasing feed intake (p = 0.080). The regression equations of MEI on ADG were MEI, kJ/kg BW0.60 d = 1.88xADG, g/d+782 (R-2 = 0.86) and MEm was estimated at 782 kJ/kg BW0.60 d. Protein retention of growing pigs would be positive while REf would be negative at this feeding level via regression equations of REp and REf on MEI.[br/] Conclusion: The MEm was estimated at 782 kJ/kg BW0.60 d in current experiment. Furthermore, growing pigs will deposit protein and oxidize fat if provided feed at the estimated maintenance level.

Metabolic alterations underlying clear cell renal cell carcinoma (ccRCC) progression include aerobic glycolysis, increased pentose phosphate pathway activity and reduced oxidative phosphorylation. Phosphofructokinase (PFK), a key enzyme of the glycolytic pathway, has L, M, and P isoforms with different tissue distributions. The mRNA level of the platelet isoform of phosphofructokinase (PFKP) is reported to be up-regulated in ccRCC patients. However, it remains unclear whether PFKP plays an important role in promoting aerobic glycolysis and macromolecular biosynthesis to support cell proliferation in ccRCC. Here we found that the up-regulated PFKP became the predominant isoform of PFK in human ccRCC. Suppression of PFKP not only impaired cell proliferation by inducing cell cycle arrest and apoptosis, but also led to decreased glycolysis, pentose phosphate pathway and nucleotide biosynthesis, accompanied by activated tricarboxylic acid cycle in ccRCC cells. Moreover, we found that p53 activation contributed to cell proliferation and metabolic defects induced by PFKP knockdown in ccRCC cells. Furthermore, suppression of PFKP led to reduced ccRCC tumor growth in vivo. Our data indicate that PFKP not only is required for metabolic reprogramming and maintaining cell proliferation, but also may provide us with a valid target for anti-renal cancer pharmaceutical agents.

This experiment was conducted to determine the effect of variety and planting year on the nutritive values of corn fed to growing pigs. Four corn varieties examined in this experiment were planted in the same village located in Longhua County, Heibei Province, China, in 2012, 2013, and 2014, respectively. During each year, corn was hand-harvested in early October and sun dried to about 14% moisture content. Three batches of twenty-four barrows (33.27±4.30, 31.88±2.93, 34.21±3.81 kg body wight [BW] in 2012, 2013, and 2014, respectively) were used and allotted to a complete block design with 4 diets and 6 replicate pigs per diet. Pigs were individually placed in metabolic crates. The four experimental diets were formulated by mixing each variety of corn and vitamins and minerals, respectively. A five-day collection period followed a seven-day diet acclimation period. The results indicated that variety of corn significantly influenced the available energy content (digestible energy [DE] on dry matter basis, p

Iron and cobalt modified vanadium titanium steel slag (VTSS) adsorbents Fe(x)–Co(y)/VTSS (with different Fe/Co molar ratios of x/y) prepared by an impregnation method were employed to remove elemental mercury (Hg0) from simulated flue gas in a wide-temperature window (150–300 °C). The samples were characterized by XRD, BET, HRTEM, EDS and H2-TPR. The effects of iron to cobalt molar ratios of x/y, capture temperature, and flue gas components (such as O2, SO2 and H2O) on the Hg0 adsorption efficiency were evaluated. The Hg0 adsorption mechanisms were proposed by XPS, TG and the pseudo-second-order kinetic model. The results showed that the increase of cobalt amount and the cooperation of Fe and Co promoted Hg0 capture. The Fe(3)–Co(3)/VTSS adsorbent exhibited the highest Hg0 removal efficiencies of 77.4% within 600 min in 6 vol% O2 at 300 °C. The presence of O2 promoted Hg0 adsorption. The influence of SO2 on the Hg0 removal efficiency was weak, while the addition of 8 vol% H2O and 500 ppm SO2 was found to have a serious inhibition effect. The XPS and TG results showed that the HgO was the major species in the captured mercury, which illustrated that Hg0 removal over Fe(x)–Co(y)/VTSS was a catalytic oxidation process. The pseudo-second-order model was demonstrated to simulate the removal of Hg0 by Fe(x)–Co(y)/VTSS and the adsorption process is controlled by chemisorption.

De novo nucleotide biosynthesis is essential for maintaining cellular nucleotide pools, the suppression of which leads to genome instability. The metabolic enzyme transketolase (TKT) in the nonoxidative branch of the pentose phosphate pathway (PPP) regulates ribose 5-phosphate (R5P) levels and de novo nucleotide biosynthesis. TKT is required for maintaining cell proliferation in human liver cancer cell lines, yet the role of TKT in liver injury and cancer initiation remains to be elucidated. In this study, we generated a liver-specific TKT knockout mouse strain by crossing TKTflox/flox mice with albumin-Cre mice. Loss of TKT in hepatocytes protected the liver from diethylnitrosamine (DEN)-induced DNA damage without altering DEN metabolism. DEN treatment of TKT-null liver increased levels of R5P and promoted de novo nucleotide synthesis. More importantly, supplementation of dNTPs in primary hepatocytes alleviated DEN-induced DNA damage, cell death, inflammatory response, and cell proliferation. Furthermore, DEN and high-fat diet (HFD)–induced liver carcinogenesis was reduced in TKTflox/floxAlb-Cre mice compared with control littermates. Mechanistically, loss of TKT in the liver increased apoptosis, reduced cell proliferation, decreased TNFα, IL6, and STAT3 levels, and alleviated DEN/HFD-induced hepatic steatosis and fibrosis. Together, our data identify a key role for TKT in promoting genome instability during liver injury and tumor initiation. Significance: These findings identify transketolase as a novel metabolic target to maintain genome stability and reduce liver carcinogenesis.

This abstract was not presented at the conference. Citation Format: Chen X, Tong Y, Chen W, Li Y, Shen K. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-04-02.

Vanadium titanium steel slag (VTSS) containing transition metal can promote the adsorption of Hg0. The method of KBr and KI impregnation was applied to modify VTSS and the properties of the adsorbents were tested. The Hg0 removal tests were carried out with a fixed bed under different conditions. The results showed that the Hg0 adsorption capacity increase with the increasing temperature. The efficiency was highest with KI(3)/VTSS at 20。C and adsorption capacity was 163.4 ug/g after 3 h. The highest Hg0 removal efficiency were 90.6% for KI(3)/VTSS, 73.5% for KBr(10)/VTSS/ VTSS at 120。C, respectively.

The objectives of this experiment were: (i) to determine the net energy (NE) of soybean oil (SBO) fed to growing pigs using indirect calorimetry (IC); and (ii) to evaluate the effects of inclusion rate of SBO on heat production, oxidative status and nutrient digestibility in growing pigs. Eighteen growing barrows were allotted to three diets based on completely randomized design with six replicate pigs (period) per diet. Diets included a corn-soybean meal basal diet and two test diets containing 5% or 10% SBO at the expense of corn and soybean meal. During each period, pigs were individually housed in metabolism crates for 14 days, including 7 days to adapt to feed, metabolism crate and environmental conditions. On day 8, pigs were transferred to the open-circuit respiration chambers for measurement of daily O2 consumption and CO2 and CH4 production. During this time, pigs were fed one of the three diets at 2.4 MJ metabolizable energy/kg body weight (BW)0.6 /day. Total feces and urine were collected and daily total heat production (THP) was measured from days 9 to 13 and fasted on day 14 to evaluate their fasting heat production (FHP). The results show that trends of decreased apparent total tract digestibility of neutral detergent fiber (linear, P = 0.09) and acid detergent fiber (linear, P = 0.07) were observed as the content of dietary lipids increased. The average THP for the three diets were 1326, 1208 and 1193 kJ/kg BW0.6 /day, respectively. The FHP of pigs averaged 843 kJ/kg BW0.6 /day and was not affected by diet characteristics. A reduction of the respiratory quotients in the fed state as the inclusion level of SBO increased was observed. In conclusion, the NE values of SBO we determined by indirect calorimetry were 33.45 and 34.05 MJ/kg dry matter under two inclusion levels. THP could be largely reduced when SBO is added in the feed, but the THP of SBO included at 5% in a corn-soybean meal diet is not different from the THP of SBO included at 10%.

Background Two experiments were conducted to estimate the net energy (NE) of corn, soybean meal, expeller-pressed rapeseed meal (EP-RSM) and solvent-extracted rapeseed meal (SE-RSM) using indirect calorimetry and to validate the NE of these four ingredients using pig growth performance. Methods In Exp.1, 24 barrows (initial BW = 36.4 ± 1.6 kg) were allotted to 1 of 4 diets which included a corn basal diet, a corn-soybean meal basal diet and two rapeseed meal diets containing 20% EP-RSM (9.5% ether extract) or SE-RSM (1.1% ether extract) substituted for corn and soybean meal. The design allowed the calculation of NE values of corn, soybean meal and rapeseed meals according to the difference method. In Exp.2, 175 growing pigs (initial BW = 36.0 ± 5.2 kg) were fed 1 of 5 diets for 28 d, with five pigs per pen and seven replications (pens) per treatment in order to validate the measured energy values. Diets were a corn-soybean meal diet and four diets including 10% or 20% EP-RSM and 10% or 20% SE-RSM. Results The NE of corn, soybean meal, EP-RSM and SE-RSM were 12.46, 11.34, 11.71 and 8.83 MJ/kg DM, respectively. The NE to ME ratio of corn (78%) was similar to tabular values, however, the NE to ME ratios of soybean meal (70%) and rapeseed meal (76%) were greater than tabular values. The greater NE value in EP-RSM than in SE-RSM is consistent with its higher EE content. Increasing EP-RSM or SE-RSM did not affect the growth performance of pigs and the caloric efficiency of NE was comparable for all diets. Conclusions The NE of EP-RSM was similar to soybean meal, and both were greater than SE-RSM. The DE, ME and NE values measured in Exp.1 are confirmed by results of Exp. 2 with comparable caloric efficiencies of DE, ME or NE for all diets.

Transcription factor carbohydrate responsive element binding protein (ChREBP) promotes glycolysis and lipogenesis in metabolic tissues and cancer cells. ChREBP-α and ChREBP-β, two isoforms of ChREBP transcribed from different promoters, are both transcriptionally induced by glucose. However, the mechanism by which glucose increases ChREBP mRNA levels remains unclear. Here we report that hepatocyte nuclear factor 4 alpha (HNF-4α) is a key transcription factor for glucose-induced ChREBP-α and ChREBP-β expression. Ectopic HNF-4α expression increased ChREBP transcription while knockdown of HNF-4α greatly reduced ChREBP mRNA levels in liver cancer cells and mouse primary hepatocytes. HNF-4α not only directly bound to an E-box-containing region in intron 12 of the ChREBP gene, but also promoted ChREBP-β transcription by directly binding to two DR1 sites and one E-box-containing site of the ChREBP-β promoter. Moreover, HNF-4α interacted with ChREBP-α and synergistically promoted ChREBP-β transcription. Functionally, HNF-4α suppression reduced glucose-dependent ChREBP induction. Increased nuclear abundance of HNF-4α and its binding to cis-elements of ChREBP gene in response to glucose contributed to glucose-responsive ChREBP transcription. Taken together, our results not only revealed the novel mechanism by which HNF-4α promoted ChREBP transcription in response to glucose, but also demonstrated that ChREBP-α and HNF-4α synergistically increased ChREBP-β transcription.

The aim of the study was to elucidate the mechanism by which advanced glycation end products (AGEs) promote cell proliferation in liver cancer cells.We treated liver cancer HepG2 cells with 200 mg/L AGEs or bovine serum albumin (BSA) and assayed for cell viability, cell cycle, and apoptosis.