A randomized, parallel controlled, open-label clinical trial was conducted to evaluate the effect of a botanic compound berberine (BBR) on NAFLD.
A randomized, parallel controlled, open-label ...clinical trial was conducted in three medical centers (NIH Registration number: NCT00633282). A total of 184 eligible patients with NAFLD were enrolled and randomly received (i) lifestyle intervention (LSI), (ii) LSI plus pioglitazone (PGZ) 15mg qd, and (iii) LSI plus BBR 0.5g tid, respectively, for 16 weeks. Hepatic fat content (HFC), serum glucose and lipid profiles, liver enzymes and serum and urine BBR concentrations were assessed before and after treatment. We also analyzed hepatic BBR content and expression of genes related to glucose and lipid metabolism in an animal model of NAFLD treated with BBR.
As compared with LSI, BBR treatment plus LSI resulted in a significant reduction of HFC (52.7% vs 36.4%, p = 0.008), paralleled with better improvement in body weight, HOMA-IR, and serum lipid profiles (all p<0.05). BBR was more effective than PGZ 15mg qd in reducing body weight and improving lipid profile. BBR-related adverse events were mild and mainly occurred in digestive system. Serum and urine BBR concentrations were 6.99ng/ml and 79.2ng/ml, respectively, in the BBR-treated subjects. Animal experiments showed that BBR located favorably in the liver and altered hepatic metabolism-related gene expression.
BBR ameliorates NAFLD and related metabolic disorders. The therapeutic effect of BBR on NAFLD may involve a direct regulation of hepatic lipid metabolism.
ClinicalTrials.gov NCT00633282.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Immunity deteriorates with age in animals but comparatively little is known about the temporal regulation of plant resistance to herbivores. The phytohormone jasmonate (JA) is a key regulator of ...plant insect defense. Here, we show that the JA response decays progressively in Arabidopsis. We show that this decay is regulated by the miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE9 (SPL9) group of proteins, which can interact with JA ZIM-domain (JAZ) proteins, including JAZ3. As SPL9 levels gradually increase, JAZ3 accumulates and the JA response is attenuated. We provide evidence that this pathway contributes to insect resistance in young plants. Interestingly however, despite the decay in JA response, older plants are still comparatively more resistant to both the lepidopteran generalist Helicoverpa armigera and the specialist Plutella xylostella, along with increased accumulation of glucosinolates. We propose a model whereby constitutive accumulation of defense compounds plays a role in compensating for age-related JA-response attenuation during plant maturation.
Pu-erh tea displays cholesterol-lowering properties, but the underlying mechanism has not been elucidated. Theabrownin is one of the most active and abundant pigments in Pu-erh tea. Here, we show ...that theabrownin alters the gut microbiota in mice and humans, predominantly suppressing microbes associated with bile-salt hydrolase (BSH) activity. Theabrownin increases the levels of ileal conjugated bile acids (BAs) which, in turn, inhibit the intestinal FXR-FGF15 signaling pathway, resulting in increased hepatic production and fecal excretion of BAs, reduced hepatic cholesterol, and decreased lipogenesis. The inhibition of intestinal FXR-FGF15 signaling is accompanied by increased gene expression of enzymes in the alternative BA synthetic pathway, production of hepatic chenodeoxycholic acid, activation of hepatic FXR, and hepatic lipolysis. Our results shed light into the mechanisms behind the cholesterol- and lipid-lowering effects of Pu-erh tea, and suggest that decreased intestinal BSH microbes and/or decreased FXR-FGF15 signaling may be potential anti-hypercholesterolemia and anti-hyperlipidemia therapies.
Display omitted
•An electrochemical sensor for SARS-CoV-2 was constructed based on a smartphone.•The signal amplification of the sensor was based on supersandwich-type recognition strategy.•The ...detectable ratios of the sensor were higher than those obtained by RT-qPCR.•The sensor has the lowest limit of detection among the published approaches to date.•The sensor showed high specificity and selectivity.
The recent pandemic outbreak of COVID-19 caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a threat to public health globally. Thus, developing a rapid, accurate, and easy-to-implement diagnostic system for SARS-CoV-2 is crucial for controlling infection sources and monitoring illness progression. Here, we reported an ultrasensitive electrochemical detection technology using calixarene functionalized graphene oxide for targeting RNA of SARS-CoV-2. Based on a supersandwich-type recognition strategy, the technology was confirmed to practicably detect the RNA of SARS-CoV-2 without nucleic acid amplification and reverse-transcription by using a portable electrochemical smartphone. The biosensor showed high specificity and selectivity during in silico analysis and actual testing. A total of 88 RNA extracts from 25 SARS-CoV-2-confirmed patients and eight recovery patients were detected using the biosensor. The detectable ratios (85.5 % and 46.2 %) were higher than those obtained using RT-qPCR (56.5 % and 7.7 %). The limit of detection (LOD) of the clinical specimen was 200 copies/mL, which is the lowest LOD among the published RNA measurement of SARS-CoV-2 to date. Additionally, only two copies (10 μL) of SARS-CoV-2 were required for per assay. Therefore, we developed an ultrasensitive, accurate, and convenient assay for SARS-CoV-2 detection, providing a potential method for point-of-care testing.
Developing efficient organic solar cells (OSCs) with thick active layers is crucial for roll‐to‐roll printing. However, thicker layers often result in lower efficiency. This study tackles this ...challenge using a polymer adsorption strategy combined with a layer‐by‐layer approach. Incorporating insulator polystyrene (PS) into the PM6:L8‐BO system creates PM6+PS:L8‐BO blends, effectively suppressing trap states and extending exciton diffusion length in the mixed donor domain. Adding insulating polymers with benzene rings to the donor enhances π–π stacking of donors, boosting intermolecular interactions and electron wave function overlap. This results in more orderly molecular stacking, longer exciton lifetimes, and higher diffusion lengths. The promoted long‐range exciton diffusion leads to high power conversion efficiencies of 19.05% and 18.15% for PM6+PS:L8‐BO blend films with 100 and 300 nm thickness, respectively, as well as a respectable 16.00% for 500 nm. These insights guide material selection for better exciton diffusion, and offer a method for thick‐film OSC fabrication, promoting a prosperous future for practical OSC mass production.
This study addresses the challenge of maintaining efficiency in thick‐film organic solar cells (OSCs). A novel polymer adsorption strategy that regulates molecular stacking, leading to enhanced intermolecular interactions. A reduction in trap states and an elongation in exciton diffusion length, resulting in a remarkable increase in power conversion efficiency in thick‐film OSCs, is achieved.
The in-situ quantitative characterization of the interface structure and properties of carbon fiber/epoxy resin composites was carried out by using peak force quantitative nanomechanical mapping ...(PF-QNM) technology in this study. The mechanism of hygrothermal damage was developed. It is found that the hygrothermal aging can be divided into three stages. In the first stage, the resin matrix and the interface absorb simultaneously moisture and the interface size increases linearly from 45.2 ± 4.1 nm to 76.2 ± 10.3 nm. The increase of the “soft interface” area makes the bending strength and interlaminar shear strength decrease by 17.3% and 15.8%, respectively. In the second stage, resin matrix undergoes secondary curing and the interface size continues to increase up to 110.8 ± 13.8 nm, resulting in the increase of the bending strength, interlaminar shear strength and impact resistance. The impact peak load and strain energy increase by 56.1% and 1286.3%, respectively. In the third stage, interface area is saturated with moisture and the size changes little and the resin continues to absorb moisture, resulting in the swells and plasticization under high temperature and high humidity. The bending strength and interlaminar shear strength of the material decrease respectively to 1185.9 ± 13.1 MPa and 53.2 ± 3.2 MPa, with a reduction of 27.6% and 28.0%.
•CFRP interface plays an important role in the overall mechanical properties of composites.•Quantitative in-situ characterization of interface supports mechanical analysis of CFRP in the hygrothermal aging.•PF-QNM based on AFM is used to characterize the interfacial structure and performance during aging.•Mechanical properties, interfacial performance and their relationship are considered.•Hygrothermal aging process of composite T700/TR1219B can be divided into three stages.
Dear Editor, Base editors （BEs） have been recently developed by combining the APOBEC （apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like）/AID （acti- vation-induced deaminase） cytidine ...deaminase family members 1 with the CRISPR./Cas9 system to perform targeted C-to-T base editing 2-8. Mechanistically, Cas9 variant-fused APOBEC/AID is directed to target site by sgRNA, introducing C-to-T substitution at the single-base level 2-4. Compared to earlier generations of BEs （BE1 and BE2）, the latest BE3 achieved much higher base editing frequencies by substituting catalyti- cally-dead Cas9 （dCas9） with Cas9 nickase （nCas9） 2.
Left-censored missing values commonly exist in targeted metabolomics datasets and can be considered as missing not at random (MNAR). Improper data processing procedures for missing values will cause ...adverse impacts on subsequent statistical analyses. However, few imputation methods have been developed and applied to the situation of MNAR in the field of metabolomics. Thus, a practical left-censored missing value imputation method is urgently needed. We developed an iterative Gibbs sampler based left-censored missing value imputation approach (GSimp). We compared GSimp with other three imputation methods on two real-world targeted metabolomics datasets and one simulation dataset using our imputation evaluation pipeline. The results show that GSimp outperforms other imputation methods in terms of imputation accuracy, observation distribution, univariate and multivariate analyses, and statistical sensitivity. Additionally, a parallel version of GSimp was developed for dealing with large scale metabolomics datasets. The R code for GSimp, evaluation pipeline, tutorial, real-world and simulated targeted metabolomics datasets are available at: https://github.com/WandeRum/GSimp.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The development of high‐performance photocatalytic systems for CO2 reduction is appealing to address energy and environmental issues, while it is challenging to avoid using toxic metals and organic ...sacrificial reagents. We here immobilize a family of cobalt phthalocyanine catalysts on Pb‐free halide perovskite Cs2AgBiBr6 nanosheets with delicate control on the anchors of the cobalt catalysts. Among them, the molecular hybrid photocatalyst assembled by carboxyl anchors achieves the optimal performance with an electron consumption rate of 300±13 μmol g−1 h−1 for visible‐light‐driven CO2‐to‐CO conversion coupled with water oxidation to O2, over 8 times of the unmodified Cs2AgBiBr6 (36±8 μmol g−1 h−1), also far surpassing the documented systems (<150 μmol g−1 h−1). Besides the improved intrinsic activity, electrochemical, computational, ex‐/in situ X‐ray photoelectron and X‐ray absorption spectroscopic results indicate that the electrons photogenerated at the Bi atoms of Cs2AgBiBr6 can be directionally transferred to the cobalt catalyst via the carboxyl anchors which strongly bind to the Bi atoms, substantially facilitating the interfacial electron transfer kinetics and thereby the photocatalysis.
A metal halide photocatalyst immobilized with a molecular catalyst achieves an optimal performance for visible‐light‐driven CO2‐to‐CO conversion coupled with water oxidation to O2, which mainly benefits from the rapid directional electron transfer from the metal halide to the catalyst via its carboxyl anchors.
Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the antigastric cancer (GC) effect of ...Guiqi Baizhu (GQBZP) and the analysis of potential key compounds, key targets, and key pathways for the therapeutic effects against GC were carried out based on the method of network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment. There were 33 proteins shared between GQBZP and GC, and 131 compounds of GQBZP had a high correlation with these proteins, indicating that the PI3K‐AKT signaling pathway might play a key role in GC. From these studies, we selected human epidermal growth factor receptor 2 (HER2) and programmed cell death 1‐ligand 1 (PD‐L1) for docking; the results showed that 385 and 189 compounds had high docking scores with HER2 and PD‐L1, respectively. Six compounds were selected for microscale thermophoresis (MST). Daidzein/quercetin and isorhamnetin/formononetin had the highest binding affinity for HER2 and PD‐L1, with Kd values of 3.7 μmol/L and 490, 667, and 355 nmol/L, respectively. Molecular dynamics simulation studies based on the docking complex structures as the initial conformation yielded the binding free energy between daidzein/quercetin with HER2 and isorhamnetin/formononetin with PD‐L1, calculated by molecular mechanics Poisson‐Boltzmann surface area, of −26.55, −14.18, −19.41, and −11.86 kcal/mol, respectively, and were consistent with the MST results. In vitro experiments showed that quercetin, daidzein, and isorhamnetin had potential antiproliferative effects in MKN‐45 cells. Enzyme activity assays showed that quercetin could inhibit the activity of HER2 with an IC50 of 570.07 nmol/L. Our study provides a systematic investigation to explain the material basis and molecular mechanism of traditional Chinese medicine in treating diseases.
We are committed to establishing a systematic research method based on network pharmacology, multitarget molecular docking, molecular dynamics simulation, and protein and experimental verification in vitro and in vivo, to establish a systematic analysis method for traditional Chinese medicine (TCM) treatment of diseases. We aim to provide a possible theoretical and experimental basis for the standardization and internationalization of TCM.
PDF
