Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparing the pharmacokinetics of daidzein and genistein with the use of 13C-labeled tracers in premenopausal women.

BACKGROUND Despite significant interest in the risks and benefits of phytoestrogens to human health, few data exist on their pharmacokinetics in humans. OBJECTIVE We investigated the pharmacokinetics of the (13)C isotopic forms of daidzein and genistein in healthy humans, specifically addressing intraindividual variability, effect of increasing intake, and influence of prolonged exposure to a soy food diet. DESIGN Premenopausal women (n = 16) were administered 0.4 mg [(13)C]daidzein or [(13)C]genistein/kg body wt orally on 3 occasions, including once after eating soy foods for 7 d. On a further occasion the dose was doubled. Plasma and urinary [(13)C]isoflavone concentrations were measured by mass spectrometry. RESULTS Serum concentrations of [(13)C]genistein and [(13)C]daidzein peaked after 5.5 and 7.4 h, respectively. The systemic bioavailability and maximum serum concentration of [(13)C]genistein were significantly greater than those of [(13)C]daidzein. The bioavailability of both isoflavones did not increase linearly when the dietary intake was doubled. The mean volume of distribution normalized to bioavailability (V(d)/F), clearance rate, and half-life of [(13)C]daidzein were 336.25 L, 30.09 L/h, and 7.75 h, respectively; the corresponding values for [(13)C]genistein were 258.76 L, 21.85 L/h, and 7.77 h. The average recovery of [(13)C]daidzein and [(13)C]genistein in urine was 30.1% and 9.0% of the dose ingested, respectively. CONCLUSIONS The serum pharmacokinetics of [(13)C]daidzein and [(13)C]genistein were reproducible among healthy women, and genistein was more bioavailable than was daidzein. Pharmacokinetics were unaffected by chronic exposure to soy foods. Urinary isoflavone concentrations correlated poorly with maximal serum concentrations, indicating the limitations of urine measurements as a predictor of systemic bioavailability. The bioavailability of both isoflavones was nonlinear at higher intakes, suggesting that uptake is rate-limiting and saturable.
Structural Basis for Eukaryotic Transcription-Coupled DNA Repair Initiation

Eukaryotic transcription-coupled repair (TCR), or transcription-coupled nucleotide excision repair (TC-NER), is an important and well-conserved sub-pathway of nucleotide excision repair (NER) that preferentially removes DNA lesions from the template strand blocking RNA polymerase II (Pol II) translocation1,2. Cockayne syndrome group B protein in humans (CSB, or ERCC6), or its yeast orthologs (Rad26 in Saccharomyces cerevisiae and Rhp26 in Schizosaccharomyces pombe), is among the first proteins to be recruited to the lesion-arrested Pol II during initiation of eukaryotic TCR1,3–10. Mutations in CSB are associated with Cockayne syndrome, an autosomalrecessive neurologic disorder characterized by progeriod features, growth failure, and photosensitivity1. The molecular mechanism of eukaryotic TCR initiation remains elusive, with several long-standing questions unanswered: How do cells distinguish DNA lesion-arrested Pol II from other forms of arrested Pol II? How does CSB interact with the arrested Pol II complex? What is the role of CSB in TCR initiation? The lack of structures of CSB or the Pol II-CSB complex have hindered our ability to answer those questions. Here we report the first structure of Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature. com/authors/editorial_policies/license.html#terms Correspondence and requests for materials should be addressed to D.W. dongwang@ucsd.edu or A.E. L. aleschziner@ucsd.edu. †These authors contributed equally to this work. Author Contributions J.X. prepared the proteins with help from W.W. and J.C. and performed the biochemical analyses. A.H. and P.D. B. provided the Py-Im chemical agent. I. L. collected the EM data with help from A.W. I. L. performed data processing and refinement with help from M.A.C. I.L. and F.D. generated the atomic models with homology models generated by J.X. , W.W. and D.W. D.W. and A.E. L wrote the manuscript with help from all lab members. D.W. and A.E. L directed and supervised the research. The authors declare no competing financial interests. HHS Public Access Author manuscript Nature. Author manuscript; available in PMC 2018 May 22. Published in final edited form as: Nature. 2017 November 30; 551(7682): 653–657. doi:10.1038/nature24658. A uhor M anscript
Microstructure, joint strength and failure mechanisms of SnPb and Pb-free solders in BGA packages

The microstructure, joint strength and failure mechanisms of SnPbAg, SnAg and SnAgCu solders on Cu/Ni/Au BGA pad metallization were investigated after multiple reflows or high temperature aging. In the SnPbAg system, a two-layer structure, i.e., Ni/sub 3/Sn/sub 4/ and (Au, Ni)Sn/sub 4/, was formed at the solder-substrate metallization interface after aging at 125, 150, and 175/spl deg/C. However, such structure was not present in the two Pb-free solder systems. Only a layer of Ni/sub 3/Sn/sub 4/ intermetallic compound in the SnAg system and a layer of Cu-Sn-Ni-Au intermetallic compound in the SnAgCu system were found at respective interfaces, even after the two solder systems had been heat treated for 1000 h at the afore-mentioned temperatures. The formation of the (Au, Ni)Sn/sub 4/ ternary compound in the SnPbAg system was due to re-settlement of Au at the interface which led to brittle failure in this system during ball shear testing. In contrast, SnAg and SnAgCu systems failed exclusively inside the solder ball during shear testing after aging at 150/spl deg/C for up to 1000 h. The two Pb-free solder systems showed good resistance to thermal aging with the solder ball shear strength being maintained at 1.60 to 1.70 kgf. The SnPbAg system degraded in mechanical performance with aging time and had strength as low as 1.20 kgf after aging at 150/spl deg/C for 1000 h. The growth rates of intermetallic compound layers at 125, 150, and 175/spl deg/C aging temperatures and the activation energy for the formation of different intermetallic compound layers were also determined in this investigation.
A Prospective Longitudinal Study on Implant Prosthetic Rehabilitation in Controlled HIV-Positive Patients with 1-Year Follow-Up: The Role of CD4+ Level, Smoking Habits, and Oral Hygiene.

BACKGROUND A recent study showed that implant-prosthetic rehabilitation in well-controlled HIV patients gave slightly worse results than in an healthy population, and failures were all linked to infection. PURPOSE The aim of this study was to examine the associations between the success of implant-prosthetic treatment and systemic CD4+ level, smoking habits, and oral hygiene. MATERIALS AND METHODS This mono-centric study included HIV patients with a stable disease and good oral hygiene requiring implant rehabilitation. Each patient received at least one dental implant. Prosthesis were delivered after 90 days in the upper jaw and 60 days in the lower jaw. Primary outcome measures were prosthetic failures, implant failures, peri-implant marginal bone level changes, and biological complications (peri-implantitis, pus, pain, paresthesia). The possible association with CD4 count, smoking habits, and oral hygiene was analyzed. RESULTS Sixty-eight patients received 194 implants, and 66 patients (190 implants) were followed for 1 year. No significant associations were found between CD4+ count, oral hygiene-associated variables, and any of the outcome measures. If compared with nonsmoking/light smoking patients, patients who smoked >10 cigarettes/day suffered a statistically significant greater number of implant failures (p ≤ .005), presented a comparatively higher number of peri-implantitis (p < .001), as well as a higher frequency of pus (p ≤ .007), and reported pain (p ≤ .009). CONCLUSION Within the limitation of the present study, placement of dental implants in HIV-positive patients with stable disease seems a reasonable treatment option, regardless of CD4+ cell count, provided that they are in a normal range. Oral hygiene variables were not influent in this group of patient following recall appointments, while HIV-positive heavy smokers (>10 cigarettes/day) demonstrated an increased risk of early implant failure, peri-implantitis, episodes of pus, and self-reported pain.
The efficacy of a local ascorbic acid-rich food in improving iron absorption from Mexican diets: a field study using stable isotopes.

BACKGROUND One potentially sustainable approach to improving iron status at the community level is to encourage the consumption of local ascorbic acid-rich foods, in conjunction with meals high in nonheme iron. OBJECTIVE The study, conducted in rural Mexico, measured stable isotopes of iron to evaluate the effect on iron absorption of the addition of 25 mg ascorbic acid as agua de limón (limeade) to 2 typical meals per day for 2 wk. DESIGN Fifteen nonpregnant, nonlactating, iron-deficient (ferritin < 12 microg/L) women (x +/- SD age: 28.3 +/- 7.7 y) fasted overnight and were brought to a community clinic. After an initial blood sample, subjects consumed 0.25 mg (57)Fe with both breakfast and lunch for 14 d. On day 29, another blood sample was taken, and a reference dose of 2.7 mg (58)Fe with 25 mg ascorbic acid was given. For the following 15 d, participants consumed 0.25 mg (57)Fe added to both breakfast and lunch with 25 mg ascorbic acid added to each meal as limeade. A final blood sample was taken on day 59. RESULTS Iron absorption was calculated from recovery of isotopes in blood obtained 14 d after administration of each isotope. When 25 mg ascorbic acid as limeade was added to test meals twice a day for 2 wk, iron absorption increased significantly (P < 0.001) in every subject: the mean absorption rose from 6.6 +/- 3.0% to 22.9 +/- 12.6%. CONCLUSIONS The consumption of 25 mg ascorbic acid as limeade twice daily with meals substantially improved iron absorption and may improve the iron status of nonpregnant, nonlactating, iron-deficient women.
A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans.

BACKGROUND High fructose consumption is suspected to be causally linked to the epidemics of obesity and metabolic disorders. In rodents, fructose leads to insulin resistance and ectopic lipid deposition. In humans, the effects of fructose on insulin sensitivity remain debated, whereas its effect on ectopic lipids has never been investigated. OBJECTIVE We assessed the effect of moderate fructose supplementation on insulin sensitivity (IS) and ectopic lipids in healthy male volunteers (n = 7). DESIGN IS, intrahepatocellular lipids (IHCL), and intramyocellular lipids (IMCL) were measured before and after 1 and 4 wk of a high-fructose diet containing 1.5 g fructose . kg body wt(-1) . d(-1). Adipose tissue IS was evaluated from nonesterified fatty acid suppression, hepatic IS from suppression of hepatic glucose output (6,6-2H2-glucose), and muscle IS from the whole-body glucose disposal rate during a 2-step hyperinsulinemic euglycemic clamp. IHCL and IMCL were measured by 1H magnetic resonance spectroscopy. RESULTS Fructose caused significant (P < 0.05) increases in fasting plasma concentrations of triacylglycerol (36%), VLDL-triacylglycerol (72%), lactate (49%), glucose (5.5%), and leptin (48%) without any significant changes in body weight, IHCL, IMCL, or IS. IHCL were negatively correlated with triacylglycerol after 4 wk of the high-fructose diet (r = -0.78, P < 0.05). CONCLUSION Moderate fructose supplementation over 4 wk increases plasma triacylglycerol and glucose concentrations without causing ectopic lipid deposition or insulin resistance in healthy humans.
Binding Functions of Microbe Cement

Microbe cement as a new technique of consolidating loose particles has drawn much attention because of the ever increasing awareness of environmental protection. The technique relies on the microbial‐induced calcite precipitation at particle–particle contacts and around individual particles. In order to further explain the binding essence of microbe cement, this paper firstly compares the effect of cementing loose particles by microbial calcite cement with that by chemical precipitated calcite. Moreover, the morphology of calcite produced by above‐mentioned two methods and the microstructure between calcite and loose sand particles are analyzed by transmission electron microscope (TEM), infra‐red spectra (IR), X‐ray photoelectron spectroscopy (XPS), and nuclear magnetic resonance (NMR), respectively. The TEM results indicate that the microbial calcite consists of many fine grains with irregular shape, however, the chemical calcite has significant growth steps. The IR, XPS, and NMR results all show that the microbial‐induced precipitation of calcite in loose sand particles interacts with other particles to generate hydrogen bond, which play a role in binding function between loose sand particles and calcite produced by microbe cement.
Impairment of small intestinal protein assimilation in patients with end-stage renal disease: extending the malnutrition-inflammation-atherosclerosis concept.

BACKGROUND Protein malnutrition is a common finding in renal disease. Recently, we showed that impaired protein assimilation (digestion and absorption) may contribute to protein malnutrition in nondiabetic patients with chronic renal failure. OBJECTIVE The aim of the present study was to evaluate whether these findings can be extended to the dialysis population. Moreover, relations with indexes of the malnutrition-inflammation-atherosclerosis (MIA) syndrome were investigated. DESIGN Protein assimilation was evaluated in 24 healthy control subjects and in 40 patients with end-stage renal disease (ESRD; 14 treated with peritoneal dialysis and 26 with hemodialysis) by means of a [13C]protein breath test, quantification of the generation rate of p-cresol, or both methods. Both approaches provide reliable information on the efficiency of protein assimilation. Breath test results were expressed as the maximum percentage recovery per hour of the administered dose of 13C (%max) and as the cumulative percentage recovery at the end of the test (%cum end). Several indexes of nutritional status, inflammation, and atherosclerosis were assessed. RESULTS Compared with the control subjects, ESRD patients had significantly lower breath-test derived indexes of protein assimilation [%max=3.75 +/- 0.30 compared with 4.90 +/- 0.25, P=0.006; %cum end=12.41 (5.74-23.22) compared with 16.87 (9.42-22.99), P=0.020] and a higher 24-h p-cresol generation rate corrected for dietary protein intake [3.89 (0.48-11.60) compared with 2.81 (0.21-11.20) mg p-cresol/g urea nitrogen; P=0.028]. The presence of impaired protein assimilation was associated with indexes of the MIA syndrome. CONCLUSION Our study provides evidence that protein assimilation is impaired in ESRD patients. Moreover, this disorder is associated with the severity of the MIA syndrome.
Hepatic ketogenesis and peripheral ketone body utilization in the ruminant.

Hepatic and alimentary ketogenesis occur at similar rates in fed, nonpregnant, nonlactating goats, sheep and dairy cows. Alimentary ketogenesis begins to diminish within 24 h after fasting but compensatory increases in hepatic ketogenesis maintain total splanchnic release and, therefore, no change in circulating concentrations of ketone bodies is observed. By the third day of fast the gut is utilizing acetoacetate and beta-hydroxybutyrate and alimentary ketogenesis has ceased. Hepatic ketogenesis of both ketone bodies accelerates rapidly due to portal-drained visceral and hindquarter lipolysis and subsequent hepatic fatty acid uptake and total circulating concentrations are doubled. During pregnancy and lactation in sheep and cows alimentary ketogenesis is maintained as long as digestible organic matter intake is constant. Hepatic and total splanchnic release of beta-hydroxybutyrate increases in late gestation and early lactation. Again, this is due to increased portal-drained visceral and hindquarter free fatty acid release and hepatic free fatty acid uptake. Hindquarter uptake of both ketones during late gestation is similar to the ratio observed in nonpregnant fed sheep but the percentage of utilization decreases, perhaps reflecting partitioning to uteroplacental tissues. Hindquarter uptake of both ketone bodies in sheep increases in early lactation due to increased circulating concentrations because extraction ratios are similar to those of fed animals. Ketosis during pregnancy in sheep and lactation in cows may be prevented by beta-hydroxybutyrate stimulation of pancreatic insulin production. However, an insulin-independent intrahepatic mechanism apparently occurs in sheep. (ABSTRACT TRUNCATED AT 250 WORDS)
Parallel activation of de novo lipogenesis and stearoyl-CoA desaturase activity after 3 d of high-carbohydrate feeding.

BACKGROUND High-carbohydrate (HC) diets increase de novo lipogenesis (DNL), but effects on stearoyl-CoA desaturase (SCD) are not so well studied. OBJECTIVE The objective was to investigate DNL and SCD in liver and adipose tissue by using fatty acid ratios after short-term dietary intervention. DESIGN Eight subjects consumed isoenergetic 3-d HC (10% fat; 75% carbohydrates) or higher fat (HF; 40% fat; 45% carbohydrates) diets (sugar to starch ratio: 60:40 for both) in a crossover study. Blood was taken from an artery and a vein draining subcutaneous adipose tissue. DNL and SCD activity were investigated by using the ratios of 16:0 to 18:2n-6 and of 16:1n-7 to 16:0, respectively. A test meal, including [U-(13)C]palmitate was given to trace dietary fatty acid incorporation into VLDL-triacylglycerol (TG). The conversion of intravenously infused [(2)H(2)]palmitic acid to [(2)H(2)]palmitoleic acid in VLDL-TG was quantified as a specific marker of hepatic SCD activity. RESULTS The VLDL-TG 16:0/18:2n-6 ratio, which reflects hepatic DNL, was greater after the HC diet than after the HF diet (P = 0.02). With the HC diet, increased plasma TG concentrations correlated with 16:0/18:2n-6 ratios (r = 0.76, P = 0.028). Plasma VLDL-TG and adipose venous nonesterified fatty acid (NEFA) 16:1n-7/16:0 ratios were higher after the HC diet (fasting: P = 0.01 and P = 0.05, respectively; postprandial: P = 0.03 and P = 0.05, respectively). Changes in fasting VLDL-TG 16:0/18:2n-6 and 16:1n-7/16:0 ratios were associated (P = 0.06). The contribution of total fatty acids from splanchnic sources (including DNL) was higher after the HC diet (P = 0.02). Expression of lipogenic genes in subcutaneous adipose tissue was not significantly affected by diet. CONCLUSION Parallel activation of DNL and SCD was found after a short period of HC feeding.
Cytochrome P-450-derived eicosanoids participate in the renal functional effects of ET-1 in the anesthetized rat.

We evaluated the contribution of cytochrome P-450 (CYP450)-dependent arachidonic acid (AA) metabolites and prostanoids to the renal hemodynamic and tubular effects of endothelin-1 (ET-1) in anesthetized rats. Either ET-1 (0.3, 1.0, and 3 pmol ⋅ kg-1 ⋅ min-1) or vehicle was infused intravenously during two to three 30-min clearance experimental periods. Only high-dose ET-1 increased mean arterial pressure: control, 75 ± 3 mmHg vs. experimental, 84 ± 4 mmHg. A dose-dependent diuretic-natriuretic response to ET-1 occurred despite progressive declines in glomerular filtration rate (GFR) and renal blood flow. In the face of a 36% reduction in GFR in response to the highest dose of ET-1, urinary sodium excretion (UNaV) increased threefold from 0.57 ± 0.11 to 1.6 ± 0.10 μmol ⋅ 100 g-1 ⋅ min-1. Indomethacin (5 mg/kg) decreased basal GFR from 1.2 ± 0.3 ml ⋅ 100 g-1 ⋅ min-1to 0.8 ± 0.1 ml ⋅ 100 g-1 ⋅ min-1and potentiated the GFR lowering action of ET-1 associated with reductions in UNaV and urine volume. Cobalt chloride (CoCl2) and dibromododec-11-enoic acid (DBDD), which diminish CYP450-dependent AA metabolism through different mechanisms, were used to identify CYP450 products mediating the renal functional actions of ET-1. DBDD (12.5 μg/min) reduced urinary excretion of 20-hydroxyeicosatetraenoic acid from 3.4 ± 0.9 (control) to 1.1 ± 0.6 ng/h and abolished the negative effects of ET-1 on GFR while decreasing the diuretic-natriuretic action of ET-1. Similar effects were produced by CoCl2. Clotrimazole, an inhibitor of epoxygenase activity, was without effect on ET-1-induced renal functional changes. Thus the capacity of ET-1 to enhance prostaglandin production was primarily expressed in terms of positive effects on renal hemodynamics. In contrast, CYP450 products promoted sodium excretion despite negative effects on renal hemodynamics.
Retrieval of time series LAI by coupling an empirical crop growth model with a radiative transfer model

Continuous LAI values are very important in crop growth monitoring, however, all of the remotely sensed LAI products are limited by the temporal and spatial resolution. High spatial resolution is good for crop monitoring but with very poor temporal sampling. The popular MODIS 8 day LAI product is still not sufficient for crop monitoring. An empirical crop growth model was developed based on two years' ground truth. It was then coupled with SAILH model to retrieve the continuous LAI day by day. A rolling inversion strategy was proposed further to minimize the random noise in the observations. The models coupled inversion was tested by simulation inversion. Results show significant improvements of the new inversion method.
Coffee consumption and reduced risk of developing type 2 diabetes: a systematic review with meta-analysis

Context Type 2 diabetes (T2D) is a major health problem worldwide that is associated with increased morbidity and mortality. There is increased interest in the value of different nutrition-based strategies for preventing the development of T2D. Objective This review aims to cover current knowledge regarding the effects of coffee consumption on development of T2D or modulation of adverse complications. A meta-analysis on coffee consumption and the risk of T2D was conducted. Moreover, bioactive components in coffee, polymorphisms, and potential underlying mechanism(s) in relation to T2D and adverse complications are discussed. Data sources PubMed was searched up to December 1, 2017, and prospective cohort and nested case-control studies of the association between coffee consumption and T2D risk were selected. Data extraction Two investigators independently extracted data from included studies. Results A total of 30 prospective studies with 1 185 210 participants and 53 018 incident T2D cases were included in the meta-analysis. The pooled relative risk (RR) was 0.71 (95% confidence interval [CI], 0.67-0.76) for the highest category of coffee consumption (median consumption, 5 cups/d) vs the lowest category (median consumption, 0 cups/d). The risk of T2D decreased by 6% (RR = 0.94; 95%CI, 0.93-0.95) for each cup-per-day increase in coffee consumption. Results were similar for caffeinated coffee consumption (per additional cup of coffee per day: RR = 0.93; 95%CI, 0.90-0.96) and decaffeinated coffee consumption (corresponding RR = 0.94; 95%CI, 0.90-0.98). Conclusions Available evidence indicates that coffee consumption is inversely associated with risk of T2D. Possible mechanisms behind this association include thermogenic, antioxidative, and anti-inflammatory effects; modulation of adenosine receptor signaling; and microbiome content and diversity.