Metabolomics analysis reveals metabolite diversity of the rare cliff plant Oresitrophe rupifraga unge.

Oresitrophe is monotypic, with the only species, Oresitrophe rupifraga Bunge, which is exclusive to China, having special growth and developmental traits due to its habitat. Furthermore, it has bright flowers and medicinal benefits. This study investigated the metabolites present in various tissues of Oresitrophe rupifraga Bunge. Using a widely targeted metabolomics approach, 1965 different metabolites were identified in Oresitrophe rupifraga Bunge. Based on principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), the aboveground and underground metabolites of Oresitrophe rupifraga differed significantly. The comparison between bulblets and leaves revealed the differential expression of 461 metabolites, whereas the comparison between rhizomes and leaves showed the differential expression of 423 metabolites, and the comparison between bulblets and rhizomes showed the differential expression of 249 metabolites. The bulblets exhibited 49 metabolites that were higher and 412 metabolites that were lower than those of the leaves, whereas the rhizomes showed 123 upregulated and 300 downregulated metabolites. Bulblets showed an increase in 18 metabolites and a decrease in 231 metabolites compared to the rhizomes. Leaves contain more phenolic acids than the rhizomes and bulblets, whereas the rhizomes and bulblets contain more terpenoids than the leaves. KEGG pathway analysis showed an association between metabolites and metabolic pathways, as well as their effect on the progression and maturation of Oresitrophe rupifraga Bunge. The research findings can provide some insight into the growth and developmental traits of Oresitrophe rupifraga Bunge, thus providing a theoretical foundation for cultivating and utilising this plant.

A meta-analysis of the value of MRI-based VBQ scores for evaluating osteoporosis.

Objective: Osteoporosis is the most common skeletal disease in humans. Early onset of osteoporosis is usually asymptomatic, so early diagnosis is critical. The purpose of this study was to analyze the value of MRI-based VBQ scores for evaluating osteoporosis. Methods: We searched PubMed, Embase, the Cochrane Library databases, Web of Science, and some Chinese electronic databases for published articles and the ClinicalTrials.gov site for completed but unpublished studies on evaluating the value of MRI-based VBQ scores for evaluating osteoporosis. We calculated the summarized sensitivity, specificity, the ROC curve (AUC) values and their 95% confidence intervals (CIs) using MetaDiSc 1.4 software and STATA. Results: Our study included 8 studies involving 999 patients of which 660 patients were diagnosed with osteopenia/osteoporosis, and 339 patients were identified as having normal BMD. The pooled sensitivity was 0.809 (95% CI, 0.777-0.838, I2 = 78.8%), the pooled specificity was 0.640 (95% CI, 0.587-0.691, I2 = 85.9%), and the pooled AUC was 0.8375. Conclusion: MRI-based VBQ scores provided high sensitivity and moderate specificity in detecting osteoporosis. Opportunistic use of VBQ scores could be considered, e.g. before lumbar spine surgery. Prospero registration number: CRD42022377024.

Preparation, characterization and in vitro antitumor activity evaluation of hyaluronic acid-alendronate-methotrexate nanoparticles.

As an anti-metabolic drug, methotrexate (MTX) plays an important role in the treatment of various malignant tumors. However, several side effects such as low selectivity and high toxic of MTX limited its further applications. With aims to increase its accumulation in the tumor sites and reduce the toxicity of normal tissue nonspecific uptake, a self-assembled hyaluronic acid-alendronate-methotrexate nanoparticle (HA-ALN-MTX NPs) with a dual-tumor-targeted drug loaded system was designed and synthesized with an average particle size of 265.6 ± 13.3 nm. The advantage of this nanosystem is that the anticancer drug MTX can be used as a tumor-targeted ligand for folate acid receptors (FA), and hyaluronic acid (HA) can be used as another tumor targeted ligand for CD44 receptors. In vitro experiments confirmed that HA-ALN-MTX NPs has lower toxic effect on normal tissue cells HUVECs and has relatively high proliferation inhibition effect on tumor cells A549. Moreover, the inhibition effect could be adjusted by altering the dose of given drugs. All these results revealed that the prepared HA-ALN-MTX NPs could be selectively taken up by tumor cells by FA and CD44 receptor-mediated endocytosis. Therefore, self-assembled HA-ALN-MTX NPs targeted by these FA/CD44 receptors for anticancer drugs could act as effective antitumor drugs.

Risk of Fractures Associated with Dipeptidyl Peptidase-4 Inhibitor Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: More and more studies suggest that type 2 diabetes mellitus (T2DM) can lead to an increased fracture risk. Some previous clinical studies and experimental data have shown that some antidiabetic drugs can increase or decrease the incidence of fractures. METHODS: We searched Medline, Embase, Cochrane Library, and the ClinicalTrials.gov website ( https://www.clinicaltrials.gov ) for published or unpublished randomized controlled trials (RCTs) from inception through 2 December 2018 to compare the effects of dipeptidyl peptidase-4 (DDP-4) inhibitors with active control drugs or placebo in T2DM patients. All RCTs had a duration of at least 12 weeks, and the ultimate measure was whether a fracture occurs or not. We calculated odds ratios and their 95% confidence intervals by the fixed effect Mantel-Haenszel model. Publication bias was investigated firstly through visual observation of funnel plot asymmetry and then through Begg's test or Egger's test. The Cochrane bias risk tools were used to assess the quality of included studies. RESULTS: Eighty-seven eligible RCTs were included in this study. Of 93,772 participants, 49,270 patients received therapy and 44,502 were control patients. Five kinds of DDP-4 inhibitors were included: sitagliptin, saxagliptin, alogliptin, linagliptin and vildagliptin. There were 676 fractures in the DDP-4 inhibitor treatment group and 646 in the control group. The median average glycosylated hemoglobin level was 8.2%. DDP-4 inhibitor treatment did not seem to influence the fracture risk, no matter whether compared with placebo or active comparators in T2DM patients (Mantel-Haenszel odds ratio (MH-OR) = 1.01, 95% CI 0.90-1.12, P = 0.92). After three subgroup analyses which were defined by drug type, control regimen and duration, the results were still stable. CONCLUSION: This systematic review and meta-analysis shows that DDP-4 inhibitors do not affect the fracture risk when compared with antidiabetic drugs or placebo in T2DM patients.

MicroRNAs in the Progress of Diabetic Nephropathy: A Systematic Review and Meta-Analysis.

BACKGROUND: We conducted a systematic review and meta-analysis of existing literature to evaluate the different outcomes of microRNAs (miRNAs) in diabetic nephropathy (DN), including urinary albumin excretion rates, urinary albumin creatinine rates, glomerular filtration rate, HbAc1, and creatinine. METHODS: Electronic databases including PUBMED, MEDLINE, and EMBASE were searched for eligible publications to July 2018. The following comparisons between treatment groups were included: normal group versus DN group; control group versus micro/macroalbuminuria group. RESULTS: Twelve eligible studies that included 2500 participants were finally recruited in this meta-analysis. Fifteen miRNAs (miRNA-21, miRNA-181b, miRNA-194, miRNA-30, miRNA-215, and others) were upregulated whereas seven miRNAs (miRNA-26a, miRNA-126, miRNA-424, miRNA-574-3p, miR-223, miR-155, and miR-192) were downregulated in the DN group compared with control groups. The miR-133b, miR-342, miR-30, miR-192, miR-194, and miR-215 were significantly correlated in urinary albumin excretion rates (r=0.33, 95% CI= 0.26-0.39). miR-192, miR-217, miR-15b, miR-34a, and miR-636 were correlated with urinary albumin creatinine rates (r=0.69; 95% CI=0.12-0.92), while miR-133b, miR-345, miR-33, miR-326, miR-574-3p, miR-126, miR-217, miR-15b, miR-34a, and miR-636 were significantly correlated with HbAc1 (r =0.23, 95% CI = 0.15-0.31). There were twelve miRNAs that were closely related to the glomerular filtration rate (r=0.28, 95% CI =0.21-0.34). Creatinine (r=0.33, 95% CI = 0.22-0.40) was significantly different between normal and DN groups. CONCLUSIONS: The meta-analysis acquired the correlations between miRNAs and outcomes including UAER, UACR, eGFR, HbAc1, and creatinine in DN. It suggested that miRNAs may participate in the pathogenesis of DN process.

Effects of surface modification of As2O3-loaded PLGA nanoparticles on its anti-liver cancer ability: An in vitro and in vivo study.

As2O3-loaded nanoparticles (NPs) based on poly (lactic-co-glycolic acid) (PLGA) were prepared by double emulsion-solvent evaporation method. Then Lactose acid (LA) and/or PEG were modified onto the NPs by chemical covalent coupling through -NH2 and -COOH. The FTIR results showed that LA and PEG could be successfully modified onto the surface of the NPs. All the As2O3-loaded PLGA NPs (As2O3@PLGA NPs) presented suitable physical stability, favorable size, and spherical shape. The in vitro release rate of As2O3 from the NPs depended on the surface of the NPs. As expected, the As2O3@PLGA-PEG/LA NPs showed a moderate release rate, the highest anticancer effects and cellular internalization against SMMC-7721 cell line. The PLGA-PEG/LA NPs could represent an effective nano-size delivery system of As2O3 for treatment of liver cancer.

Active summer carbon storage for winter persistence in trees at the cold alpine treeline.

The low-temperature limited alpine treeline is one of the most obvious boundaries in mountain landscapes. The question of whether resource limitation is the physiological mechanism for the formation of the alpine treeline is still waiting for conclusive evidence and answers. We therefore examined non-structural carbohydrates (NSC) and nitrogen (N) in treeline trees (TATs) and low-elevation trees (LETs) in both summer and winter in 11 alpine treeline cases ranging from subtropical monsoon to temperate continental climates across Eurasia. We found that tissue N concentration did not decrease with increasing elevation at the individual treeline level, but the mean root N concentration was lower in TATs than in LETs across treelines in summer. The TATs did not have lower tissue NSC concentrations than LETs in summer. However, the present study with multiple tree species across a large geographical scale, for the first time, revealed a common phenomenon that TATs had significantly lower NSC concentration in roots but not in the aboveground tissues than LETs in winter. Compared with LETs, TATs exhibited both a passive NSC storage in aboveground tissues in excess of carbon demand and an active starch storage in roots at the expense of growth reduction during the growing season. This starch accumulation disappeared in winter. Our results highlight some important aspects of the N and carbon physiology in relation to season in trees at their upper limits. Whether or to what extent the disadvantages of winter root NSC and summer root N level of TATs affect the growth of treeline trees and the alpine treeline formation needs to be further studied.

Long noncoding RNA Gomafu upregulates Foxo1 expression to promote hepatic insulin resistance by sponging miR-139-5p.

Long non-coding RNA Gomafu is involved in diabetes-related diseases. However, its role in insulin resistance (IR) remains unclear. Our objective is to explore the role of Gomafu in hepatic IR and glucose intolerance. Gomafu expression was determined in livers of ob/ob mice and high-fat diet (HFD) mice. The binding activity of NF-κB on the Gomafu promoter was measured by chromatin immunoprecipitation and quantitative real-time PCR assays. Increased Gomafu expression was observed in the livers of obese mice. Besides, the binding of NF-κB on the Gomafu promoter was also observed in hepatocytes from ob/ob mice. Further study showed that knockdown of NF-κB p65 alleviated the increase in hepatic Gomafu expression in vivo and in vitro. Knockdown of hepatic Gomafu inhibited hepatic glucose production (HGP) and improved insulin sensitivity in obese mice, whereas, overexpression of hepatic Gomafu resulted in an increase in random and fasting blood glucose levels in lean mice. In addition, we demonstrated that Gomafu functioned as miR-139 sponge and led to the de-repression of its target gene Foxo1, which played an important role in gluconeogenesis and HGP in hepatocytes. Finally, silenced Foxo1 expression abolished the effect of Gomafu overexpression on gluconeogenesis and glucose production in hepatocytes. Taken together, our data suggested that the increase in Gomafu expression contributed to hepatic IR in obese mice.

Associations between VDR Gene Polymorphisms and Osteoporosis Risk and Bone Mineral Density in Postmenopausal Women: A systematic review and Meta-Analysis.

Results on the relationships between vitamin D receptor (VDR) gene polymorphisms and postmenopausal osteoporosis (PMOP) susceptibility and bone mineral density (BMD) are conflicting. The aim of the study is to identify more eligible studies that calculated pooled OR and WMD with 95% CI to assess their associations. Overall, there were significant correlations between VDR ApaI, VDR FokI and PMOP susceptibility. Subgroup analysis showed that VDR ApaI polymorphism significantly decreased the osteoporosis risk in Caucasian postmenopausal women. In Asian populations, VDR BsmI and VDR FokI were associated with an increased risk of PMOP. As to the associations between VDR polymorphisms and BMD, Caucasian PMOP women carrying the ApaI aa genotype were at risk of high BMD in femoral neck, and low femoral neck BMD was observed in Caucasian PMOP women with FokI Ff genotype. PMOP women with the Cdx2 GA genotype had a lower lumbar spine BMD in overall and Caucasian populations compared with PMOP women with GG genotype. Different VDR gene polymorphisms have different impacts on PMOP risk and BMD.

Effects of mistletoe removal on growth, N and C reserves, and carbon and oxygen isotope composition in Scots pine hosts.

Most mistletoes are xylem-tapping hemiparasites, which derive their resources from the host's xylem solution. Thus, they affect the host's water relations and resource balance. To understand the physiological mechanisms underlying the mistletoe-host relationship, we experimentally removed Viscum album ssp. austriacum (Wiesb.) Vollmann from adult Pinus sylvestris L. host trees growing in a Swiss dry valley. We analyzed the effects of mistletoe removal over time on host tree growth and on concentrations of nonstructural carbohydrates (NSC) and nitrogen (N) in needles, fine roots and sapwood. In addition, we assessed the δ(13)C and δ(18)O in host tree rings. After mistletoe removal, δ(13)C did not change in newly produced tree rings compared with tree rings in control trees (still infected with mistletoe), but δ(18)O values increased. This pattern might be interpreted as a decrease in assimilation (A) and stomatal conductance (gs), but in our study, it most likely points to an inadequacy of the dual isotope approach. Instead, we interpret the unchanged δ(13)C in tree rings upon mistletoe removal as a balanced increase in A and gs that resulted in a constant intrinsic water use efficiency (defined as A/gs). Needle area-based concentrations of N, soluble sugars and NSC, as well as needle length, single needle area, tree ring width and shoot growth, were significantly higher in trees from which mistletoe was removed than in control trees. This finding suggests that mistletoe removal results in increased N availability and carbon gain, which in turn leads to increased growth rates of the hosts. Hence, in areas where mistletoe is common and the population is large, mistletoe management (e.g., removal) may be needed to improve the host vigor, growth rate and productivity, especially for relatively small trees and crop trees in xeric growth conditions.

HRD1-Mediated IGF-1R Ubiquitination Contributes to Renal Protection of Resveratrol in db/db Mice.

Many studies have provided evidence to demonstrate the beneficial renal effects of resveratrol (RESV) due to its antioxidant character and its capacity for activation of surtuin 1. However, the molecular mechanisms underlying the protective role of RESV against kidney injury are still incompletely understood. The present study used Lepr db/db (db/db) and Lepr db/m (db/m) mice as models to evaluate the effect of RESV on diabetic nephropathy (DN). RESV reduced proteinuria and attenuated the progress of renal fibrosis in db/db mice. Treatment with RESV markedly attenuated the diabetes-induced changes in renal superoxide dismutase copper/zinc, superoxide dismutase manganese, catalase, and malonydialdehyde as well as the renal expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), α-smooth muscle actin (α-SMA), and E-cadherin in db/db mice. The kidney expression of the IGF-1 receptor (IGF-1R) was increased in db/db mice, but the expression of 3-hydroxy-3-methylglutaryl reductase degradation (HRD1), a ubiquitin E3 ligase, was significantly decreased in the DN model. RESV treatment dramatically decreased IGF-1R and increased HRD1 expressions, consistent with data obtained with HKC-8 cells. HRD1 physically interacted with IGF-1R in HKC-8 cells and liquid chromatography and tandem mass spectrometry (LC-MS/MS) data supported the concept that IGF-1R is one of the HRD1 substrates. HRD1 promoted the IGF-1R ubiquitination for degradation in HKC-8 cells, and the down-regulation of HRD1 reversed the protective effects of RESV in HKC-8 cells. In summary, we have demonstrated that RESV reduces proteinuria and attenuates the progression of renal fibrosis in db/db mice. These protective effects of RESV on DN were associated with the up-regulation of HRD1, induced by RESV, and the promotion of IGF-1R ubiquitination and degradation.

A decrease in hepatic microRNA-9 expression impairs gluconeogenesis by targeting FOXO1 in obese mice.

AIM/HYPOTHESIS: MicroRNA-9 (miR-9) is involved in the regulation of pancreatic beta cell function. However, its role in gluconeogenesis is still unclear. Our objective was to investigate the role of miR-9 in hepatic glucose production (HGP). METHODS: MiR-9 expression was measured in livers of high-fat diet (HFD) mice and ob/ob mice. The methylation status of the miR-9-3 promoter regions in hepatocytes was determined by the methylation-specific PCR procedure. The binding activity of DNA methyltransferase (DNMT)1, DNMT3a and DNMT3b on the miR-9-3 promoter was detected by chromatin immunoprecipitation (ChIP) and quantitative real-time PCR assays. HGP was evaluated in vitro and in vivo. Glucose tolerance, insulin tolerance and pyruvate tolerance tests were also performed. RESULTS: Reduced miR-9 expression and hypermethylation of the miR-9-3 promoter were observed in the livers of obese mice. Further study showed that the binding of DNMT1, but not of DNMT3a and DNMT3b, to the miR-9-3 promoter was increased in hepatocytes from ob/ob mice. Knockdown of DNMT1 alleviated the decrease in hepatic miR-9 expression in vivo and in vitro. Overexpression of hepatic miR-9 improved insulin sensitivity in obese mice and inhibited HGP. In addition, deletion of hepatic miR-9 led to an increase in random and fasting blood glucose levels in lean mice. Importantly, silenced forkhead box O1 (FOXO1) expression reversed the gluconeogenesis and glucose production in hepatocytes induced by miR-9 deletion. CONCLUSIONS/INTERPRETATION: Our observations suggest that the decrease in miR-9 expression contributes to an inappropriately activated gluconeogenesis in obese mice.

Long noncoding RNA MALAT1 promotes hepatic steatosis and insulin resistance by increasing nuclear SREBP-1c protein stability.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is implicated in liver cell proliferation. However, its role in hepatic steatosis and insulin resistance remain poorly understood. The aim of this study was to investigate the effects of MALAT1 on hepatic lipid accumulation and its potential targets. As expected, MALAT1 expression is increased in hepatocytes exposed to palmitate and livers of ob/ob mice. Knockdown of MALAT1 expression dramatically suppressed palmitate-induced lipid accumulation and the increase of nuclear SREBP-1c protein in HepG2 cells. In addition, RNA immunoprecipitation and RNA pull-down assay confirmed that MALAT1 interacted with SREBP-1c to stabilize nuclear SREBP-1c protein. Finally, injection of si-MALAT1 prevented hepatic lipid accumulation and insulin resistance in ob/ob mice. In conclusion, our observations suggest that MALAT1 promotes hepatic steatosis and insulin resistance by increasing nuclear SREBP-1c protein stability.

Pancreatic hyperplasia after gastric bypass surgery in a GK rat model of non-obese type 2 diabetes.

Gastric bypass surgery produces clear antidiabetic effects in a substantial proportion of morbidly obese patients. In view of the recent trend away from 'bariatric' surgery and toward 'metabolic' surgery, it is important to elucidate the enhancing effect of bypass surgery on pancreatic ß-cell mass, which is related to diabetes remission in non-obese patients. We investigated the effects of gastric bypass surgery on glycemic control and other pancreatic changes in a spontaneous non-obese type 2 diabetes Goto-Kakizaki rat model. Significant improvements in postprandial hyperglycemia and plasma c-peptide level were observed when glucose was administered orally post-surgery. Other important events observed after surgery were enhanced first phase insulin secretion in a in site pancreatic perfusion experiment, pancreatic hyperplasia, improved islet structure (revealed by immunohistochemical analysis), striking increase in ß-cell mass, slight increase in ratio of ß-cell area to total pancreas area, and increased number of small islets closely related to exocrine ducts. No notable changes were observed in ratio of ß-cell to non-ß endocrine cell area, ß-cell apoptosis, or ß-cell proliferation. These findings demonstrate that gastric bypass surgery in this rat model increases endocrine cells and pancreatic hyperplasia, and reflect the important role of the gastrointestinal system in regulation of metabolism.

Retinol binding protein 4 correlates with and is an early predictor of carotid atherosclerosis in type 2 diabetes mellitus patients.

The association of retinol binding protein 4 (RBP4) with atherosclerosis of the carotid artery in type 2 diabetes mellitus (T2DM) remains undefined. We aimed to investigate the correlation of RBP4 expression with atherosclerosis of the carotid artery in T2DM. A total of 1,076 subjects were investigated for intima-media thickness of the bilateral common carotid arteries, and they were divided into three groups: in group I, patients had normal neck vascular ultrasound, in group II, intimal carotid artery media thickness was equal to or more than 1 mm, and in group III, carotid artery plaque was present. Height, weight, blood pressure (BP), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (Apo A-1), apolipoprotein B (Apo B) and lipoprotein (a) (Lp(a)) were determined by routine laboratory methods. RBP4 and high sensitivity C reactive protein (HsCRP) were measured by an enzyme-linked immuno-sorbent assay, and insulin concentration was measured by an electrochemiluminescence sandwich immunoassay. Duration of diabetes, waist and BP, FPG, HbA1c, TG, TC, LDL-C, APOB, Lp(a), HsCRP, RBP4 and homeostasis model assessment insulin resistance index (HOMA-IR) were significantly lower in group I than in the other two groups (P<0.01, P<0.01). Plasma levels of HbA1c, RBP4, LDL-C, TC, HOMA-IR, HsCRP and Lp(a), waist and BP were significantly increased in group III than in group II (P<0.01). Multivariate logistic regression analysis showed that there were seven factors associated with the occurrence of carotid artery atherosclerosis and its risks in descending order were: high LDL-C, high waist, high HsCRP, duration of diabetes, high HOMA-IR, HbA1c and high RBP4. Our finding supported that RBP4 was positively correlated with carotid atherosclerosis in patients with T2DM and could be used as an early predictor of cardiovascular disease.

Synthesis, biocompatible, and self-assembly properties of poly (ethylene glycol)/lactobionic acid-grafted chitosan.

Polymers with targeted ligands are widely used as the anti-cancer drug delivery materials. For applications of chitosan as an anti-liver cancer drug delivery, poly (ethylene glycol)/lactobionic acid-grafted chitosan (PEG/LA-CS) was prepared and investigated since lactobionic acid can be specifically recognized by the hepatocytes. The structure of the PEG/LA-CS was characterized by Fourier transform infrared spectrometry and elemental analysis. The self-assembly behaviors of the PEG/LA-CS were monitored by steady-state fluorescence spectroscopy and electronic transmission microscope. The protein adsorption of the PEG/LA-CS was detected with bovine serum albumin (BSA) by electrochemical impedance spectroscopy. The results showed that the PEG/LA-CS almost did not adsorb protein. To study the effects of PEG/LA-CS on the structure of BSA, the interactions between the PEG/LA-CS and BSA were detected by ultraviolet spectrum, fluorescence spectrum, and circular dichroism. All the data gave one result that BSA maintained its original folded confirmation in PEG/LA-CS solution. The hemocompatibility of PEG/LA-CS was investigated by observing the effects of PEG/LA-CS on the hemolysis rate and the plasma recalcification time (PRT). The results showed that the PRT was prolonged greatly and the hemolysis rate was less than 5%. Furthermore, PEG/LA-CS also showed good cytocompatibility with K562, Hep G2, and LO2 cells. Therefore, the PEG/LA-CS is believed to have great potential for producing injectable anti-liver cancer drug delivery.

Association of Rev-erbα in adipose tissues with Type 2 diabetes mellitus amelioration after gastric bypass surgery in Goto-Kakizaki rats.

We estimated the key molecules related to Type 2 diabetes mellitus (T2DM) in adipose, liver, and muscle tissues, from nonobese diabetic Goto-Kakizaki (GK) rats and their Wistar controls, by computationally analyzing the expression profiles in open source data. With the aid of information from previous reports, Rev-erbα in adipose tissue emerged as one of the most plausible candidates. Here, in animal models, including GK rats surgically treated to ameliorate T2DM, we examined the association of Rev-erbα in adipose tissue with T2DM progression. After analyses of the Rev-erbα mRNA expression in the adipose tissue of our animal models, we compared the Rev-erbα protein expression levels in the adipose, liver, and muscle tissues of GK and Wistar controls at the ages of 1 mo (M), 3M, and 6M. The Rev-erbα protein levels in adipose tissue showed a distinctive pattern, with the negative correlation of an increasing trend in GK rats, and a decreasing trend in Wistar rats during aging, from those in liver and muscle tissues. Moreover, dysregulation of the circadian Rev-erbα expression in the adipose tissue of 6-mo-old GK rats was also observed. In particular, we ameliorated T2DM in GK rats by gastric bypass surgery, and revealed that T2DM amelioration in diabetic GK rats was associated with improved circadian Rev-erbα expression, in a comparison between the surgically treated and untreated GK rats. The roles of Rev-erbα in adipose tissue were further investigated by observations of Rev-erbα-related molecules, with reference to previous reports.

Needle-age related variability in nitrogen, mobile carbohydrates, and δ13C within Pinus koraiensis tree crowns.

For both ecologists and physiologists, foliar physioecology as a function of spatially and temporally variable environmental factors such as sunlight exposure within a tree crown is important for understanding whole tree physiology and for predicting ecosystem carbon balance and productivity. Hence, we studied concentrations of nitrogen (N), non-structural carbohydrates (NSC = soluble sugars + starch), and δ(13)C in different-aged needles within Pinus koraiensis tree crowns, to understand the needle age- and crown position-related physiology, in order to test the hypothesis that concentrations of N, NSC, and δ(13)C are needle-age and crown position dependent (more light, more photosynthesis affecting N, NSC, and δ(13)C), and to develop an accurate sampling strategy. The present study indicated that the 1-yr-old needles had significantly higher concentration levels of mobile carbohydrates (both on a mass and an area basis) and N(area) (on an area basis), as well as NSC-N ratios, but significantly lower levels of N(mass) (on a mass basis) concentration and specific leaf area (SLA), compared to the current-year needles. Azimuthal (south-facing vs. north-facing crown side) effects were found to be significant on starch [both on a mass (ST(mass)) and an area basis (ST(area))], δ(13)C values, and N(area), with higher levels in needles on the S-facing crown side than the N-facing crown side. Needle N(mass) concentrations significantly decreased but needle ST(mass), ST(area), and δ(13)C values significantly increased with increasing vertical crown levels. Our results suggest that the sun-exposed crown position related to photosynthetic activity and water availability affects starch accumulation and carbon isotope discrimination. Needle age associated with physiological activity plays an important role in determining carbon and nitrogen physiology. The present study indicates that across-scale sampling needs to carefully select tissue samples with equal age from a comparable crown position.

Responses of fine roots and soil N availability to short-term nitrogen fertilization in a broad-leaved Korean pine mixed forest in northeastern China.

Knowledge of the responses of soil nitrogen (N) availability, fine root mass, production and turnover rates to atmospheric N deposition is crucial for understanding fine root dynamics and functioning in forest ecosystems. Fine root biomass and necromass, production and turnover rates, and soil nitrate-N and ammonium-N in relation to N fertilization (50 kg N ha(-1) year(-1)) were investigated in a temperate forest over the growing season of 2010, using sequential soil cores and ingrowth cores methods. N fertilization increased soil nitrate-N by 16% (P<0.001) and ammonium-N by 6% (P<0.01) compared to control plots. Fine root biomass and necromass in 0-20 cm soil were 13% (4.61 vs. 5.23 Mg ha(-1), P<0.001) and 34% (1.39 vs. 1.86 Mg ha(-1), P<0.001) less in N fertilization plots than those in control plots. The fine root mass was significantly negatively correlated with soil N availability and nitrate-N contents, especially in 0-10 cm soil layer. Both fine root production and turnover rates increased with N fertilization, indicating a rapid underground carbon cycling in environment with high nitrogen levels. Although high N supply has been widely recognized to promote aboveground growth rates, the present study suggests that high levels of nitrogen supply may reduce the pool size of the underground carbon. Hence, we conclude that high levels of atmospheric N deposition will stimulate the belowground carbon cycling, leading to changes in the carbon balance between aboveground and underground storage. The implications of the present study suggest that carbon model and prediction need to take the effects of nitrogen deposition on underground system into account.