Dietary folate drives methionine metabolism to promote cancer development by stabilizing MAT IIA.

Folic acid, served as dietary supplement, is closely linked to one-carbon metabolism and methionine metabolism. Previous clinical evidence indicated that folic acid supplementation displays dual effect on cancer development, promoting or suppressing tumor formation and progression. However, the underlying mechanism remains to be uncovered. Here, we report that high-folate diet significantly promotes cancer development in mice with hepatocellular carcinoma (HCC) induced by DEN/high-fat diet (HFD), simultaneously with increased expression of methionine adenosyltransferase 2A (gene name, MAT2A; protein name, MATIIα), the key enzyme in methionine metabolism, and acceleration of methionine cycle in cancer tissues. In contrast, folate-free diet reduces MATIIα expression and impedes HFD-induced HCC development. Notably, methionine metabolism is dynamically reprogrammed with valosin-containing protein p97/p47 complex-interacting protein (VCIP135) which functions as a deubiquitylating enzyme to bind and stabilize MATIIα in response to folic acid signal. Consistently, upregulation of MATIIα expression is positively correlated with increased VCIP135 protein level in human HCC tissues compared to adjacent tissues. Furthermore, liver-specific knockout of Mat2a remarkably abolishes the advocating effect of folic acid on HFD-induced HCC, demonstrating that the effect of high or free folate-diet on HFD-induced HCC relies on Mat2a. Moreover, folate and multiple intermediate metabolites in one-carbon metabolism are significantly decreased in vivo and in vitro upon Mat2a deletion. Together, folate promotes the integration of methionine and one-carbon metabolism, contributing to HCC development via hijacking MATIIα metabolic pathway. This study provides insight into folate-promoted cancer development, strongly recommending the tailor-made folate supplement guideline for both sub-healthy populations and patients with cancer expressing high level of MATIIα expression.

BCAA-BCKA axis regulates WAT browning through acetylation of PRDM16.

The link between branched-chain amino acids (BCAAs) and obesity has been known for decades but the functional role of BCAA metabolism in white adipose tissue (WAT) of obese individuals remains vague. Here, we show that mice with adipose tissue knockout of Bcat2, which converts BCAAs to branched-chain keto acids (BCKAs), are resistant to high-fat diet-induced obesity due to increased inguinal WAT browning and thermogenesis. Mechanistically, acetyl-CoA derived from BCKA suppresses WAT browning by acetylation of PR domain-containing protein 16 (PRDM16) at K915, disrupting the interaction between PRDM16 and peroxisome proliferator-activated receptor-γ (PPARγ) to maintain WAT characteristics. Depletion of BCKA-derived acetyl-CoA robustly prompts WAT browning and energy expenditure. In contrast, BCKA supplementation re-establishes high-fat diet-induced obesity in Bcat2 knockout mice. Moreover, telmisartan, an anti-hypertension drug, significantly represses Bcat2 activity via direct binding, resulting in enhanced WAT browning and reduced adiposity. Strikingly, BCKA supplementation reverses the lean phenotype conferred by telmisartan. Thus, we uncover the critical role of the BCAA-BCKA axis in WAT browning.

Follow-up study of neurodevelopment in 2-year-old infants who had suffered from neonatal hypoglycemia.

BACKGROUND: Neonatal hypoglycemia is tightly related to adverse neurodevelopmental and brain injury outcomes. METHODS: A total of 195 infants who were born from diabetic mothers with a low blood glucose level (< 2.6 mM) within 0.5 h after birth were enrolled in this prospective cohort study. Of these, 157 infants who had neonatal hypoglycemia (group A) were followed up, and this group was further divided into A1 [blood glucose concentration (BGC) < 2.6 mM at < 2 h after birth], A2 (BGC < 2.6 mM at 2-24 h after birth), and A3 (BGC < 2.6 mM at > 24 h after birth). A total of 144 infants whose mothers had no high risk for gestational diabetes mellitus were followed up as the control group during the same period. The neurodevelopment of the infants was evaluated by the Gesell scoring method. RESULTS: The adaptability in the A2 and A3 subgroups was significantly lower than that in the control group (73.9 ± 6.6 vs. 87.9 ± 11.2; 71.5 ± 8.9 vs. 87.9 ± 11.2, respectively). There were significantly more mothers who used insulin during the perinatal period in A3 than in A1 and A2 (31% vs. 2%; 31% vs. 7.9%, respectively). The mothers of babies in subgroups A2 and A3 gained more weight than those of the control group (15.3 ± 1.9 kg vs. 11.1 ± 2.2 kg; 14.8 ± 2.6 kg vs. 11.1 ± 2.2 kg, respectively). CONCLUSIONS: Long and repeated neonatal hypoglycemia caused poor adaptability. The babies of mothers who used insulin or had a high weight gain during pregnancy were associated with severe or persistent neonatal hypoglycemia.

Effect of early administration of probiotics on gut microflora and feeding in pre-term infants: a randomized controlled trial.

BACKGROUND: This study aimed to evaluate the effect of early probiotic administration on gut microflora and influence on feeding in pre-term infants. METHODS: A double-blind, randomized, controlled clinical study was conducted to assess the effect of probiotics [live, combined lactobacillus and bifidobacterium (LCB)] supplementation in pre-term infants. Sixty hospitalized pre-term babies were randomly assigned to two groups: a probiotics-supplemented group and the control group. The primary endpoint was measurement of lactobacillus and bifidobacterium in the gut. The secondary outcome was the rate of feeding intolerance. RESULTS: In the first weekend, the quantity of gut lactobacillus and bifidobacterium was significantly higher in the probiotics-supplemented group than in the control group [7.84 ± 0.35 versus 6.39 ± 0.53 (log copy number/g wet fecal weight), p = 0.013; 8.52 ± 0.23 versus 7.01 ± 0.48, p = 0.024, respectively]. In the second weekend, the amount of gut lactobacillus and bifidobacterium in the probiotics-supplemented group remained significantly higher (8.62 ± 0.28 versus 7.34 ± 0.59, p = 0.036 and 9.45 ± 0.64 versus 7.85 ± 0.43, p = 0.007, respectively). Fewer patients in the probiotics-supplemented group developed a feeding intolerance (13.3% versus 46.7%, p = 0.013). CONCLUSIONS: Probiotic supplementation in the hospitalized pre-term infants in the first 2 weeks of life resulted in higher amounts of lactobacillus and bifidobacterium in the gut and a concomitant lower rate of feeding intolerance.

A High-Density Genetic Linkage Map for Cucumber (Cucumis sativus L.): Based on Specific Length Amplified Fragment (SLAF) Sequencing and QTL Analysis of Fruit Traits in Cucumber.

High-density genetic linkage map plays an important role in genome assembly and quantitative trait loci (QTL) fine mapping. Since the coming of next-generation sequencing, makes the structure of high-density linkage maps much more convenient and practical, which simplifies SNP discovery and high-throughput genotyping. In this research, a high-density linkage map of cucumber was structured using specific length amplified fragment sequencing, using 153 F2 populations of S1000 × S1002. The high-density genetic map composed 3,057 SLAFs, including 4,475 SNP markers on seven chromosomes, and spanned 1061.19 cM. The average genetic distance is 0.35 cM. Based on this high-density genome map, QTL analysis was performed on two cucumber fruit traits, fruit length and fruit diameter. There are 15 QTLs for the two fruit traits were detected.

Second trimester maternal serum triple screening marker levels in normal twin and singleton pregnancies.

The aim of the present study was to evaluate the serum levels of α-fetoprotein (AFP), free-ß-human chorionic gonadotropin (free-ß-hCG) and unconjugated estriol (uE3) in second trimester maternal serum and comparative analysis of serum markers levels in normal twin and singleton pregnancies, and to evaluate the feasible methods for the screening performances of triple markers in twin pregnancy. The levels of maternal serum markers were measured by magnetic microparticle chemiluminescence immunoassay in the second trimester. TCSoft was used for calculating the risk of Down's syndrome (DS). The marker levels were compared between the twin and singleton pregnancies, along with gestational age, and the weight or age of the pregnant women. The concentrations of the maternal serum markers were higher on average in twin compared to in singleton pregnancies in the second trimester of the gestation. The levels of AFP were 2-fold higher in twin compared to those in singleton pregnancies in weeks 16, 17 and total gestational weeks. For free-ß-hCG, the levels were higher in 15 and 18 gestational weeks. However, significant differences were found in all the gestational weeks for uE3. There was no correlation between the levels of markers and weight or age in the twin pregnancies. The serum marker levels of AFP, free-ß-hCG and uE3 in normal twins were not all 2-fold higher compared to singleton pregnancies. The current singleton gestational age-specific model for DS screening requires further correction so that it is feasible for screening in twin pregnancies.

Transcriptome profiling of trichome-less reveals genes associated with multicellular trichome development in Cucumis sativus.

Trichomes on plants, similar to fine hairs on animal and human bodies, play important roles in plant survival and development. They also represent a useful model for the study of cell differentiation. Although the regulatory gene network of unicellular trichome development in Arabidopsis thaliana has been well studied, the genes that regulate multicellular trichome development remain unclear. We confirmed that Cucumis sativus (cucumber) trichomes are multicellular and unbranched, but identified a spontaneous mutant, trichome-less (tril), which presented a completely glabrous phenotype. We compared the transcriptome profilings of the tril mutant and wild type using the Illumina HiSeq 2000 sequencing technology. A total of 991 genes exhibited differential expression: 518 were up-regulated and 473 were down-regulated. We further identified 62 differentially expressed genes that encoded crucial transcription factors and were subdivided into seven categories: homeodomain, MADS, MYB, and WRKY domains, ethylene-responsive, zinc finger, and other transcription factor genes. We further analyzed the tissue-expression profiles of two candidate genes, GLABRA2-like and ATHB51-like, using qRT-PCR and found that these two genes were specifically expressed in the epidermis and trichomes, respectively. These results and the tril mutant provide useful tools to study the molecular networks associated with multicellular trichome development.

[Properties of maize stalk biochar produced under different pyrolysis temperatures and its sorption capability to naphthalene].

Biochar was made from maize stalk under three different temperatures of 300, 500 and 700 degreeC. The elemental composition of biochar was measured by elemental analyzer. Scanning electron microscope (SEM) was used to measure the surface morphology. Sorption of naphthalene to biochar was researched by batch sorption experiments. Results showed that, with the increase of temperature, C content increased from 66. 79% to 76. 30% , H and O contents decreased from 4.92% and 19. 25% to 3. 18% and 9.53%, respectively; H/C, O/C, (O + N)/C, aromaticity and hydrophobicity increased, and polarity decreased. SEM results showed that maize stalk biochar was platy particles, and its roughness of surface increased with increasing temperature. The sorption of naphthalene on biochar followed the Lagergren pseudo-second order dynamic sorption model. Initial sorption rate and equilibrium sorption capacity increased as preparation temperatures increased at the same initial concentration of naphthalene. The isotherm sorption behavior can be described by the Freundlich model, which indicated that, as pyrolysis temperature increased, the sorption capacity of biochar increased, and nonlinearity increased first and then decreased. Biochar derived from maize stalk had distinct features when compared with other feedstocks, and its elemental composition, surface features and sorption behaviors were significantly influenced by pyrolysis temperature.

Effectiveness of combining plasma exchange with continuous hemodiafiltration on acute Fatty liver of pregnancy complicated by multiple organ dysfunction.

Acute fatty liver of pregnancy (AFLP) is a rare disease of progressive hepatic insufficiency and secondary systemic complications that induce significant maternal risk. The application of combining plasma exchange (PE) and continuous hemodiafiltration (CHDF) is a novel concept for patients with AFLP. Since 2002, we have utilized the combination of PE with CHDF as adjunctive medical therapy for 11 AFLP patients with multiple organ dysfunction. Before PE and CHDF initiation, four patients had signs and symptoms of encephalopathy, four required ventilatory support, and all 11 were developing liver failure, significant renal compromise, and coagulopathy. PE combined with CHDF for patients was initiated a mean of 2 days postpartum (range, days 0-3). Daily or every other day PE combined with CHDF was undertaken on two to eight occasions for each of the 11 patients. Ten patients responded with composite clinical and laboratory improvement and were discharged to the ward, then cured and discharged from hospital; one patient died of septic shock. Average duration of hospitalization was 17 days (range, days 9-38) from time of admission to discharge; the average duration of intensive care unit was 10 days (range, days 4-23). No significant PE- and CHDF-related complications occurred. These results indicate that combing PE and CHDF in a series-parallel circuit is an effective and safe treatment for patients with severe AFLP. This finding may have important implications for the development of an effective treatment for patients with AFLP suffering multiple organ dysfunction.

[The effects of joint administration of 6% hydroxyethyl starch 130/0.4 and high-volume hemofiltration on patients with acute lung injury and acute kidney injury].

OBJECTIVE: To evaluate the effects of administration of 6% hydroxyethyl starch (6% HES 130/0.4, voluven) in combination with high volume hemofiltration (HVHF) in patients with ALI and AKI. METHODS: One hundred and eight patients with acute lung injury (ALI) and acute kidney injury (AKI) were enrolled from Department of Intensive Care Unit (ICU) of the provincial Hospital Affiliated to Shandong University between August 2006 and May 2011. The patients were randomly divided into two groups A (n = 68) and B (n = 40) to receive voluven (i.v., for volume resuscitation) and voluven+HVHF for 72 hours. The arterial blood lactate concentration (Lac), high sensitivity C-reactive protein (hs-CRP) serum concentration, pulmonary function index alveolar-arterial oxygen pressure difference [P(A-a)DO2] and oxygenation index (OI), as well as kidney function index serum cystatin C (Cyst C) and serum creatinine clearance rate (CCr) were measured at the time of admission and 72 hours after the treatment for statistical analysis. RESULTS: In comparison with group A, group B had significantly (all P < 0.01) lower mean value in the level of arterial Lac (mmol/L: 1.7 ± 0.7 vs. 2.7 ± 1.5), serum hs-CRP (mg/L: 35.8 ± 18.8 vs. 99.5 ± 20.4), P(A-a)DO2 (mm Hg, 1 mm Hg=0.133 kPa: 115.5 ± 23.1 vs. 155.4 ± 27.4), Cyst C (mg/L: 2.06 ± 1.12 vs. 3.95 ± 2.06) and significantly higher (both P < 0.01) mean value of OI (mm Hg: 295.2 ± 38.8 vs. 239.5 ± 32.7) and CCr (ml/min: 108.71 ± 31.33 vs. 90.21 ± 30.35) 72 hours after treatment. The mortality rate of group B was significantly lower than group A [10.00%(4/40) vs. 29.41%(20/68), P < 0.05] 7 days after the admission. CONCLUSION: 6% HES 130/0.4 in combination with HVHF could improve the lung and kidney function of the patients with ALI and AKI, prevent the development of multiple organ dysfunction syndrome (MODS), therefore improve the survival rate of these patients.

[Determination of trace lead and iron in nickel chloride and manganese sulfate by flame atomic absorption spectrometry after coprecipitation with yttrium phosphate].

Using yttrium phosphate as the coprecipitation collector for the separation and preconcentration of trace lead and iron in nickel chloride and manganese sulfate, flame atomic absorption spectrometric (FAAS) determination was described in the present paper. Coprecipitation parameters including the pH of the solution, and the amounts of YCl3 and H3 PO4 were discussed. It was found that lead and iron in nickel chloride could be coprecipitated quantitatively in the range of pH 3.0-4.0, and so could be lead in manganese sulfate. The detection limits (3sigma) of lead and iron in 20 mL solution were 1.63 x 10(-2) mg x L(-1) and 4.58 x 10(-2) mg x L(-1) respectively. In NiCl2 solution the standard addition recoveries for lead and iron were 100.91% and 99.73% respectively, and in MnSO4 solution the standard addition recoveries were 99.45% and 98.98% respectively. The method has eliminated the interference of matrix, and the result is satisfied.

[Determination of trace copper and cadmium in water by flame atomic absorption spectrometry coupled with flow injection on-line preconcentration using air segmentation].

The flow injection on-line preconcentration with a knotted reactor (KR) system for the determination of copper and cadmium in water by flame atomic absorption spectrometry (FAAS) was described in the present paper. The precipitation preconcentration of trace copper and cadmium was achieved by on-line merging of the sample and ammonia solutions. The resultant precipitates were on-line collected by a knotted reactor (KR) without filtration, and then the authors used a process of air segmentation. A solution of 1 mol x L(-1) HNO3 was employed to dissolve the collected precipitates and to deliver the analyte into the FAAS system for on-line detection. With a sample loading flow rate of 4.4 mL x min(-1) and a preconcentration time of 90 s, the enhancement factor was 34 (for Cu) and 36 (for Cd) as compared with the conventional FAAS method. The detection limits (3sigma) are found to be 1.9 and 0.3 microg x L(-1) for copper and cadmium respectively. The precision (RSD, n = 11) was found to be 2.3% at the level of 30.0 microg x L(-1) of Cu (II), and 2.6% at the level of 20.0 microg x L(-1) of Cd (II). The proposed method has been successfully applied to the determination of Cu (II) and Cd (II) in water samples.