Membrane-free electrodeionization using graphene composite electrode to purify copper-containing wastewater.

Membrane-free electrodeionization (MFEDI) technology involves in situ electric regeneration of ion exchange resin, and is used to efficiently purify copper-containing wastewater, so that both the wastewater and copper may be reused. The electrode is the core functional component of a MFEDI system. Electrode-selection greatly influences the electric regeneration efficiency, water recovery and energy consumption of MFEDI processes. In this study, a graphene composite electrode was developed to improve MFEDI-system performance. A graphene composite electrode and conventional platinum-plated titanium electrode were both characterized by scanning electron microscopy (SEM) and electrochemical testing. Furthermore, the treatment and electrical regeneration properties of MFEDI systems with these two electrodes were investigated. The specific surface area of the electrode increased after graphene loading, while the oxygen evolution potential decreased. Wastewater treatment experiments demonstrated that MFEDI systems with graphene composite electrodes effectively removed copper from wastewater. The study also highlighted that the electroregeneration efficiency of the MFEDI system was improved by loading with graphene; the average copper concentration in the regeneration solution increased by 1.4 times to 50.4 mg/L, while the energy consumption decreased from 1.55 to 1.48 kWh/m3, and the water recovery rate increased from 85 to 90%.

Advanced electrochemical treatment of real biotreated petrochemical wastewater by boron doped diamond anode: performance, kinetics, and degradation mechanism.

Petrochemical wastewater is difficult to process because of various types of pollutants with high toxicity. With the improvement in the national discharge standard, traditional biochemical treatment methods may not meet the standards and further advanced treatment techniques would be required. In this study, electrochemical oxidation with boron doped diamond (BDD) anode as post-treatment was carried out for the treatment of real biotreated petrochemical wastewater. The effects of current density, pH value, agitation rate, and anode materials on chemical oxygen demand (COD) removal and current efficiency were studied. The results revealed the appropriate conditions to be a current density of 10 mA·cm-2, a pH value of 3, and an agitation rate of 400 rpm. Moreover, as compared with the graphite electrode, the BDD electrode had a higher oxidation efficiency and COD removal efficiency. Furthermore, GC-MS was used to analyze the final degradation products, in which ammonium chloride, formic acid, acetic acid, and malonic acid were detected. Finally, the energy consumption was estimated to be 6.24 kWh·m-3 with a final COD of 30.2 mg·L-1 at a current density of 10 mA·cm-2 without the addition of extra substances. This study provides an alternative for the upgrading of petrochemical wastewater treatment plants.

GPR120 suppresses adipose tissue lipolysis and synergizes with GPR40 in antidiabetic efficacy.

GPR40 and GPR120 are fatty acid sensors that play important roles in glucose and energy homeostasis. GPR40 potentiates glucose-dependent insulin secretion and demonstrated in clinical studies robust glucose lowering in type 2 diabetes. GPR120 improves insulin sensitivity in rodents, albeit its mechanism of action is not fully understood. Here, we postulated that the antidiabetic efficacy of GPR40 could be enhanced by coactivating GPR120. A combination of GPR40 and GPR120 agonists in db/db mice, as well as a single molecule with dual agonist activities, achieved superior glycemic control compared with either monotherapy. Compared with a GPR40 selective agonist, the dual agonist improved insulin sensitivity in ob/ob mice measured by hyperinsulinemic-euglycemic clamp, preserved islet morphology, and increased expression of several key lipolytic genes in adipose tissue of Zucker diabetic fatty rats. Novel insights into the mechanism of action for GPR120 were obtained. Selective GPR120 activation suppressed lipolysis in primary white adipocytes, although this effect was attenuated in adipocytes from obese rats and obese rhesus, and sensitized the antilipolytic effect of insulin in rat and rhesus primary adipocytes. In conclusion, GPR120 agonism enhances insulin action in adipose tissue and yields a synergistic efficacy when combined with GPR40 agonism.

Quantifying rates of glucose production in vivo following an intraperitoneal tracer bolus.

Aberrant regulation of glucose production makes a critical contribution to the impaired glycemic control that is observed in type 2 diabetes. Although isotopic tracer methods have proven to be informative in quantifying the magnitude of such alterations, it is presumed that one must rely on venous access to administer glucose tracers which therein presents obstacles for the routine application of tracer methods in rodent models. Since intraperitoneal injections are readily used to deliver glucose challenges and/or dose potential therapeutics, we hypothesized that this route could also be used to administer a glucose tracer. The ability to then reliably estimate glucose flux would require attention toward setting a schedule for collecting samples and choosing a distribution volume. For example, glucose production can be calculated by multiplying the fractional turnover rate by the pool size. We have taken a step-wise approach to examine the potential of using an intraperitoneal tracer administration in rat and mouse models. First, we compared the kinetics of [U-13C]glucose following either an intravenous or an intraperitoneal injection. Second, we tested whether the intraperitoneal method could detect a pharmacological manipulation of glucose production. Finally, we contrasted a potential application of the intraperitoneal method against the glucose-insulin clamp. We conclude that it is possible to 1) quantify glucose production using an intraperitoneal injection of tracer and 2) derive a "glucose production index" by coupling estimates of basal glucose production with measurements of fasting insulin concentration; this yields a proxy for clamp-derived assessments of insulin sensitivity of endogenous production.

Disposition into Adipose Tissue Determines Accumulation and Elimination Kinetics of the Cholesteryl Ester Transfer Protein Inhibitor Anacetrapib in Mice.

The cholesteryl ester transfer protein (CETP) inhibitor anacetrapib exhibits a long terminal half-life (t½) in humans; however, the dispositional mechanisms that lead to this long t½ are still being elucidated. As it is hypothesized that disposition into adipose tissue and binding to CETP might play a role, we sought to delineate the relative importance of these factors using a preclinical animal model. A multiple-dose pharmacokinetic study was conducted in C57BL6 wild-type (WT) lean, WT diet-induced obese (DIO), natural flanking region (NFR) CETP-transgenic lean, and NFR-DIO mice. Mice were dosed orally with 10 mg/kg anacetrapib daily for 42 days. Drug concentrations in blood, brown and white adipose tissue, liver, and brain were measured up to 35 weeks postdose. During dosing, a 3- to 9-fold accumulation in 72-hour postdose blood concentrations of anacetrapib was observed. Drug concentrations in white adipose tissue accumulated ∼20- to 40-fold, whereas 10- to 17-fold accumulation occurred in brown adipose and approximately 4-fold in liver. Brain levels were very low (<0.1 µM), and a trend of accumulation was not seen. The presence of CETP as well as adiposity seems to play a role in determining the blood concentrations of anacetrapib. The highest blood concentrations were observed in NFR DIO mice, whereas the lowest concentrations were seen in WT lean mice. In adipose and liver tissue, higher concentrations were seen in DIO mice, irrespective of the presence of CETP. This finding suggests that white adipose tissue serves as a potential depot and that disposition into adipose tissue governs the long-term kinetics of anacetrapib in vivo.

Characteristic time courses of cortical and medullary sodium signals measured by noninvasive (23) Na-MRI in rat kidney induced by furosemide.

BACKGROUND: To characterize regional kidney sodium response by MRI following NKCC2 inhibition. METHODS: Regional renal sodium signals were monitored noninvasively using (23) Na-MRI at 9.4T with a temporal resolution of 1.5 min in anesthetized rats (N = 14). A mild NKCC2 inhibition was induced using a slow intravenous furosemide infusion. Time course of sodium signal was modeled as an exponential transient with a single characteristic time constant. RESULTS: Under normal physiological conditions, the renal sodium signals in medullary and cortical regions were stable and found to respond differently to furosemide challenge. Furosemide infusion at 1.2 mg/kg/h (N = 7) increased sodium signal in the cortex by 40 ± 6% (P < 7 × 10(-5) ) whereas decreased in the medulla by 29 ± 2% (P < 3 × 10(-6) ) with different temporal kinetics. The characteristic time constants of the change were determined to be: 8 ± 2 and 70 ± 10 min for medulla and cortex. Also, the medullary change occurred 9(±3) times faster than cortical independent of furosemide infusion rate up to 35 mg/kg/h. CONCLUSION: The pharmacological effects in terms of regional kidney sodium signal changes induced by NKCC2 inhibition are region-specific and highly predictable. Using noninvasive sodium MRI, we obtained regional renal sodium kinetics data sets in response to a low dose furosemide infusion in normal rats.

The antiangiogenic effect of total saponins of Panax japonicus C.A. Meyer in rheumatoid arthritis is mediated by targeting the HIF-1α/VEGF/ANG-1 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese herbal medicine Panax japonicus C.A. Meyer has a long history in clinical treatment of rheumatoid arthritis (RA). Total saponins of Panax japonicus C.A. Meyer (TSPJs) were extracted from the root of Panax japonicus C.A. Meyer, and its anti-rheumatism mechanism is still unclear. AIM OF THE STUDY: To investigate whether TSPJs attenuated synovial angiogenesis in RA and explore the potential mechanisms. MATERIALS AND METHODS: Potential TSPJs targets involving gene function were predicted by network pharmacology related databases. Bioinformatics analysis and molecular docking technology were used to predict the mechanism of TSPJs in the treatment of RA. The predicted results were validated by cell experiments and a collagen-induced arthritis (CIA) mouse model. RESULTS: Bioinformatics analysis results showed that TSPJs may inhibit RA-related angiogenesis through the hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) pathways. In vitro, different doses of TSPJs showed a good inhibitory effect on the tube formation of EA.hy926 cells. The results of the cellular thermal shift assay indicated that TSPJs can bind to the HIF-1α, VEGFA, and angiopoietin-1 (ANG-1) proteins. In vivo, the administration of TSPJs alleviated the symptoms of CIA mice, including the arthritis index, hind paw thickness, and swollen joint count. The histological results demonstrated that TSPJs inhibited inflammation, angiogenesis, bone damage, and cartilage destruction. Furthermore, TSPJs decreased the number of vessels and the expression level of CD31. The mechanistic results revealed that TSPJs decreased the expression of HIF-1α, VEGFA, and ANG-1 in the serum or synovial tissues of CIA mice. CONCLUSION: These results suggest that TSPJs effectively inhibit angiogenesis in RA, and the mechanism may be related to inhibiting the HIF-1α/VEGF/ANG-1 axis.

Machine-learning-based models assist the prediction of pulmonary embolism in autoimmune diseases: A retrospective, multicenter study.

BACKGROUND: Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD. METHODS: In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort. RESULTS: In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone. CONCLUSION: ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE. TRIAL REGISTRATION: Chictr.org.cn: ChiCTR2200059599.

De novo characterization of the Anthurium transcriptome and analysis of its digital gene expression under cold stress.

BACKGROUND: Anthurium andraeanum is one of the most popular tropical flowers. In temperate and cold zones, a much greater risk of cold stress occurs in the supply of Anthurium plants. Unlike the freeze-tolerant model plants, Anthurium plants are particularly sensitive to low temperatures. Improvement of chilling tolerance in Anthurium may significantly increase its production and extend its shelf-life. To date, no previous genomic information has been reported in Anthurium plants. RESULTS: Using Illumina sequencing technology, we generated over two billion base of high-quality sequence in Anthurium, and demonstrated de novo assembly and annotation of genes without prior genome information. These reads were assembled into 44,382 unigenes (mean length = 560 bp). Based on similarity search with known protein in the non-redundant (nr) protein database, 27396 unigenes (62%) were functionally annotated with a cut-off E-value of 10-5. Further, DGE tags were mapped to the assembled transcriptome for gene expression analysis under cold stress. In total, 4363 differentially expressed genes were identified. Among these genes, 292, 805 and 708 genes were up-regulated after 1-h, 5-h and 24-h cold treatment, respectively. Then we mapped these cold-induced genes to the KEGG database. Specific enrichment was observed in photosynthesis pathway, metabolic pathways and oxidative phosphorylation pathway in 1-h cold-treated plants. After a 5-h cold treatment, the metabolic pathways and oxidative phosphorylation pathway were significantly identified as the top two pathways. After 24-h cold treatment, mRNA surveillance pathway, RNA transport pathway and plant-pathogen interaction pathway were significantly enriched. Together, a total of 39 cold-inducible transcription factors were identified, including subsets of AP2/ERF, Zinc figure, NAC, MYB and bZIP family members. CONCLUSION: Our study is the first to provide the transcriptome sequence resource for Anthurium plants, and demonstrate its digital gene expression profiling under cold conditions using the assembled transcriptome data for reference. These data provides a valuable resource for genetic and genomic studies under abiotic conditions for Anthurium plants.

Lymphatic absorption, metabolism, and excretion of a therapeutic peptide in dogs and rats.

The objective of the current study was to evaluate the mechanism of absorption and metabolism of a PEGylated peptide, MRL-1 (46 kDa), after s.c. dosing in dogs and rats. Thoracic lymph duct-cannulated (LDC) dog and rat models were developed that allowed continuous collection of lymph for up to 8 days. When [(3)H]MRL-1 was administered s.c. to LDC dogs, ∼73% of the administered radioactivity was recovered in pooled lymph over a period of 120 hours, suggesting that lymphatic uptake is the major pathway of s.c. absorption for this peptide. In agreement with these data, the systemic exposure of radioactivity related to [(3)H]MRL-1 in LDC dogs was decreased proportionately when compared with that in noncannulated control dogs. After i.v. dosing with [(3)H]MRL-1 in LDC dogs, 20% of the administered radioactivity was recovered in pooled lymph over 168 hours, suggesting some level of recirculation of radioactivity related to [(3)H]MRL-1 from the plasma compartment into the lymphatic system. Experiments conducted in the LDC rat model also resulted in similar conclusions. Analysis of injection site s.c. tissue showed significant metabolism of [(3)H]MRL-1, which provides an explanation for the <100% bioavailability of therapeutic proteins and peptides after s.c. dosing. After s.c. dosing, the major circulating components in plasma were the parent peptide and the PEG-linker [(3)H]MRL-2. The metabolism profiles in lymph were similar to those in plasma, suggesting that the loss of peptide was minimal during lymphatic transport. After i.v. dosing in rats, [(3)H]MRL-1 was metabolized and excreted primarily in the urine as metabolites.

Evaluation of selective inhibitors of 11ß-HSD1 for the treatment of hypertension.

In an effort to understand the origin of blood-pressure lowering effects observed in recent clinical trials with 11ß-HSD1 inhibitors, we examined a set of 11ß-HSD1 inhibitors in a series of relevant in vitro and in vivo assays. Select 11ß-HSD1 inhibitors reduced blood pressure in our preclinical models but most or all of the blood pressure lowering may be mediated by a 11ß-HSD1 independent pathway.

Benefit-risk assessment of traditional Chinese medicine preparations of sinomenine using multicriteria decision analysis (MCDA) for patients with rheumatoid arthritis.

OBJECTIVE: A multicriteria decision analysis (MCDA) model was used to evaluate the benefits and risks of traditional Chinese medicine preparations of sinomenine alone or in combination with conventional drugs in the treatment of rheumatoid arthritis (RA) and to provide a basis for the rational clinical application of sinomenine. METHODS: A study search was performed using six major databases, and Review Manager 5.3 was used for data analysis. Then, an MCDA model evaluation system was established for the treatment of RA with sinomenine preparations, and the benefit values, risk values, and total benefit-risk values of sinomenine preparations alone or in combination with conventional drugs were calculated using Hiview 3.2 software. Finally, Monte Carlo simulations were performed using Crystal Ball embedded in Excel software to calculate the 95% confidence intervals (95% CI), and the probability of the differences between the 2 drug regimens was determined to optimize the evaluation results. RESULTS: Forty-four randomized controlled trials (RCTs) were included. Quantitative assessment of the MCDA model showed that the sinomenine preparation alone offered less benefits than when combined with conventional drugs with a benefit difference of 20 (95% CI 3.06, 35.71). However, the risk of the combination was significantly lower with a risk difference of 13(95% CI -10.26, 27.52). The total value of the benefit-risk of sinomenine alone and in combination with conventional drugs was 46 and 53 at 60% and 40% of the benefit-risk ratio of the two dosing regimens, respectively, with a difference of 7 (95% CI -4.26, 22.12). The probability that the comprehensive score of the combined regimen is greater than that of sinomenine alone is 90.1%, and the evaluation was steady. CONCLUSION: The benefit-risk of the combined application regimen of sinomenine is greater than that of sinomenine alone.

Differential effects of oxyntomodulin and GLP-1 on glucose metabolism.

Glucagon-like peptide-1 (GLP-1) and oxyntomodulin (OXM) are peptide hormones secreted postprandially from the gut that stimulate insulin secretion in a glucose-dependent manner. OXM activates both the GLP-1 receptor (GLP1R) and the glucagon receptor (GCGR). It has been suggested that OXM acutely modulates glucose metabolism solely through GLP1R agonism. Because OXM activates the GLP1R with lower affinity than GLP-1, we generated a peptide analog (Q→E, OXMQ3E) that does not exhibit glucagon receptor agonist activity but retains the same affinity as OXM for GLP1R. We compared the effects of OXM and OXMQ3E in a glucose tolerance test and, to better characterize the effect on glucose metabolism, we performed controlled infusions of OXM or OXMQ3E during a hyperglycemic clamp performed in wild-type, Glp1r(-/-), and Gcgr(-/-) mice. Our findings show that OXM, but not OXMQ3E, activates the GCGR in vivo. Second, OXM and OXMQ3E improve glucose tolerance following an acute glucose challenge and during a hyperglycemic clamp in mice. Finally, OXM infusion during a glucose clamp reduces the glucose infusion rate (GIR) despite a simultaneous increase in insulin levels in Glp1r(-/-) mice, whereas OXM and OXMQ3E increase GIR to a similar extent in Gcgr(-/-) mice. In conclusion, activation of the GCGR seems to partially attenuate the acute beneficial effects on glucose and contributes to the insulinotropic action of oxyntomodulin.

Lymphatic transport and catabolism of therapeutic proteins after subcutaneous administration to rats and dogs.

The mechanism underlying subcutaneous absorption of macromolecules and factors that can influence this process were studied in rats using PEGylated erythropoietins (EPOs) as model compounds. Using a thoracic lymph duct cannulation (LDC) model, we showed that PEGylated EPO was absorbed from the subcutaneous injection site mainly via the lymphatic system in rats, which is similar to previous reports in sheep. After subcutaneous administration, the serum exposure was reduced by ∼70% in LDC animals compared with that in the control animals, and most of the systemically available dose was recovered in the lymph. In both LDC and intact rats, the total radioactivity recoveries in excreta after subcutaneous administration were high (70-80%), indicating that catabolism, not poor absorption, was the main cause for the observed low bioavailability (30-40%). Moreover, catabolism of PEGylated EPO was found with both rat subcutaneous tissue homogenate and lymph node cell suspensions, and a significant amount of dose-related breakdown fragments was found in the lymph of LDC rats. In addition, the bioavailability of PEGylated EPOs was shown to be 2- to 4-fold lower in "fat rats," indicating that physiologic features pertinent to lymphatic transport can have a profound impact on subcutaneous absorption. Limited studies in dogs also suggested similar subcutaneous absorption mechanisms. Collectively, our results suggest that the lymphatic absorption mechanism for macromolecules is probably conserved among commonly used preclinical species, e.g., rats and dogs, and that mechanistic understanding of the subcutaneous absorption mechanism and associated determinants should be helpful in biologic drug discovery and development.

Molecular characterization of cultivated bromeliad accessions with Inter-Simple Sequence Repeat (ISSR) Markers.

Bromeliads are of great economic importance in flower production; however little information is available with respect to genetic characterization of cultivated bromeliads thus far. In the present study, a selection of cultivated bromeliads was characterized via inter-simple sequence repeat (ISSR) markers with an emphasis on genetic diversity and population structure. Twelve ISSR primers produced 342 bands, of which 287 (~84%) were polymorphic, with polymorphic bands per primer ranging from 17 to 34. The Jaccard's similarity ranged from 0.08 to 0.89 and averaged ~0.30 for the investigated bromeliads. The Bayesian-based approach, together with the un-weighted paired group method with arithmetic average (UPGMA)-based clustering and the principal coordinate analysis (PCoA), distinctly grouped the bromeliads from Neoregelia, Guzmania, and Vriesea into three separately clusters, well corresponding with their botanical classifications; whereas the bromeliads of Aechmea other than the recently selected hybrids were not well assigned to a cluster. Additionally, ISSR marker was proven efficient for the identification of hybrids and bud sports of cultivated bromeliads. The findings achieved herein will further our knowledge about the genetic variability within cultivated bromeliads and therefore facilitate breeding for new varieties of cultivated bromeliads in future as well.

Comparative electrochemical oxidation of the secondary effluent of petrochemical wastewater with electro-Fenton and anodic oxidation with supporting electrolytes.

Electro-Fenton (EF) oxidation has high oxidation abilities and is widely used in the treatment of biorefractory and chemically refractory organic wastewater. However, it generates a large amount of iron sludge, which limits large-scale application. In this work, the comparative study of EF oxidation and anodic oxidation (AO) of the secondary effluent of petrochemical wastewater using boron doped diamond anode is carried out. In EF oxidation, the effects of Fe2+ concentration, pH value, and current density are investigated. The optimal conditions consist of the following: Fe2+ concentration of 1.5 mmol·L-1, pH of 4, and current density of 10 mA·cm-2. In AO process, the effect of adding SO42-, Cl-, NO3-, PO43-, and CO32- is investigated; the optimal conditions can be obtained by adding a Na2SO4 solution (0.075 mol·L-1). When compared with AO, although EF oxidation has a higher treatment efficiency, its energy consumption is higher, and the generated effluent (with 155 g of iron sludge·m-3) dramatically increases the post-treatment cost, thereby limiting its large-scale application. For AO with Na2SO4 solution (0.075 mol·L-1) and a COD removal efficiency of 70%, the corresponding treatment time is 1.34 h and the energy consumption is 2.44 kWh·m-3.

Discovery of novel, potent, selective, and orally active human glucagon receptor antagonists containing a pyrazole core.

A novel class of 1,3,5-pyrazoles has been discovered as potent human glucagon receptor antagonists. Notably, compound 26 is orally bioavailable in several preclinical species and shows selectivity towards cardiac ion channels, other family B receptors such hGIP and hGLP1, and a large panel of enzymes and additional receptors. When dosed orally, compound 26 is efficacious in suppressing glucagon induced plasma glucose excursion in rhesus monkey and transgenic murine pharmacodynamic models at 1 and 10 mpk, respectively.

Total glucosides of paeony for the treatment of rheumatoid arthritis: A methodological and reporting quality evaluation of systematic reviews and meta-analyses.

OBJECTIVE: To assess the methodological, reporting and evidence quality of systematic reviews and meta-analyses of total glucosides of paeony (TGP) for rheumatoid arthritis (RA). METHODS: We comprehensively searched the literature in numerous databases from inception to July 29th, 2020. Two appraisers collected data and assessed the methodological and reporting quality of the included reviews by revised A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) tool and the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA), respectively. The level of evidence quality was evaluated by employing the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) scale. RESULTS: Eleven relevant articles were collected. The results from AMSTAR-2 showed that the methodological quality of all included reviews was critically low; no authors met the standard of those critical domains (0%), particularly in item 2, item 4 and item 7. The PRISMA scores ranged from 16.5 to 25, and one meta-analysis almost conformed to the PRISMA structure. According to GRADE, the 11 studies included 59 outcomes: 27 had very low quality, 22 had low quality, 10 had moderate quality, and none had high quality evidence. The most prominent downgrading factors were risk of bias, followed by publication bias, inconsistency, imprecision, and indirectness. CONCLUSIONS: Although included studies summarized that TGP was effective and safe in the treatment of RA, the methodological and reporting quality and the quality of evidence was poor overall; decision-makers should be prudent when using TGP in treating RA patients. High-quality and multicenter studies investigating TGP for RA are urgently needed.

Molecular Profiling Reveals a Common Metabolic Signature of Tissue Fibrosis.

Fibrosis, or the accumulation of extracellular matrix, is a common feature of many chronic diseases. To interrogate core molecular pathways underlying fibrosis, we cross-examine human primary cells from various tissues treated with TGF-ß, as well as kidney and liver fibrosis models. Transcriptome analyses reveal that genes involved in fatty acid oxidation are significantly perturbed. Furthermore, mitochondrial dysfunction and acylcarnitine accumulation are found in fibrotic tissues. Substantial downregulation of the PGC1α gene is evident in both in vitro and in vivo fibrosis models, suggesting a common node of metabolic signature for tissue fibrosis. In order to identify suppressors of fibrosis, we carry out a compound library phenotypic screen and identify AMPK and PPAR as highly enriched targets. We further show that pharmacological treatment of MK-8722 (AMPK activator) and MK-4074 (ACC inhibitor) reduce fibrosis in vivo. Altogether, our work demonstrate that metabolic defect is integral to TGF-ß signaling and fibrosis.

Piriformospora indica-induced phytohormone changes and root colonization strategies are highly host-specific.

Piriformospora indica, an endophytic fungus of Sebacinales, has a wide host range and promotes the performance of mono- and eudicot plants. Here, we compare the interaction of P. indica with the roots of seven host plants (Anthurium andraeanum, Arabidopsis thaliana, Brassica campestris, Lycopersicon esculentum, Oncidium orchid, Oryza sativa, and Zea mays). Microscopical analyses showed that the colonization time and the mode of hyphal invasion into the roots differ in the symbiotic interactions. Substantial differences between the species were also observed for the levels and accumulation of jasmonate (JA) and gibberellin (GA) and the transcript levels for genes involved in their syntheses. No obvious correlation could be detected between the endogenous JA and/or GA levels and the time point of root colonization in a given plant species. Our results suggest that root colonization strategies and changes in the two phytohormone levels are highly host-specific.