The episodic growth of high-elevation orogenic plateaux is controlled by a series of geodynamic processes. However, determining the underlying mechanisms that drive plateau growth dynamics over ...geological history and constraining the depths at which growth originates, remains challenging. Here we present He-CO
-N
systematics of hydrothermal fluids that reveal the existence of a lithospheric-scale fault system in the southeastern Tibetan Plateau, whereby multi-stage plateau growth occurred in the geological past and continues to the present. He isotopes provide unambiguous evidence for the involvement of mantle-scale dynamics in lateral expansion and localized surface uplift of the Tibetan Plateau. The excellent correlation between
He/
He values and strain rates, along the strike of Indian indentation into Asia, suggests non-uniform distribution of stresses between the plateau boundary and interior, which modulate southeastward growth of the Tibetan Plateau within the context of India-Asia convergence. Our results demonstrate that deeply-sourced volatile geochemistry can be used to constrain deep dynamic processes involved in orogenic plateau growth.
It is suggested that microRNAs play important roles in the development of various cancers. Here, we showed that miR-137 is downregulated in glioblastoma (GBM) cell lines and that low levels of ...miR-137 are associated with a poor prognostic phenotype of GBM patients. Ectopic expression of miR-137 significantly inhibited GBM cell proliferation and angiogenesis. In addition, ectopic expression of miR-137 inhibited tumor growth and angiogenesis in a SCID mouse xenograft model. EZH2 was identified as a direct target of miR-137 by using luciferase reporter and Western blot assays, and EZH2 overexpression can rescue the inhibitory effect of miR-137 on cell proliferation and angiogenesis. Furthermore, tumor samples from GBM patients showed an inverse relationship between miR-137 and EZH2 levels. Our results suggest that miR-137 may serve as a biomarker in GBM, and the modulation of its activity may represent a novel therapeutic strategy for the treatment of GBM patients.
The deposition of amyloid-β (Aβ) plaques and formation of neurotoxic reactive oxygen species (ROS) is a significant pathological signature of Alzheimer’s disease (AD). Herein, a novel strategy is ...reported for combining the unique Aβ absorption property of selenium nanoparticles with the natural antioxidant agent chlorogenic acid (CGA) to form CGA@SeNPs. The in vitro biological evaluation revealed that CGA could clear the ROS induced by Aβ40 aggregates, but it did not inhibit the Aβ40 aggregation and cell membrane damage which were also caused by Aβ40 aggregates. Interestingly, CGA@SeNPs show an enhanced inhibition effect on Aβ40 aggregation and, more importantly, protect PC12 cells from Aβ aggregation-induced cell death. It is believed that CGA@SeNPs are more efficient than CGA in reducing Aβ40 toxic in long-term use.
Smilax china
L. is an important herb used in traditional Chinese medicine. In this study, the mechanism of
Smilax china
L. polyphenols (SCP) on insulin resistance and anti-obesity in mice induced by ...a high-fat diet (HFD) was investigated. Fifty female mice were randomly divided into five groups: control, HFD and low, medium, and high doses of SCP for 70 d. SCP significantly decreased intraperitoneal adipose tissue index, body weight gain, liver lipids, and serum inflammatory factor levels. Blood glucose and insulin concentrations, as well as insulin resistance index in SCP, were significantly lower than those in HFD. In addition, SCP markedly up-regulated the gene expression of glucose transporter 4 (GLUT4), insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), serine-threonine kinase (AKT), Acyl-CoA oxidase (ACO), and protein kinase A (PKA), and down-regulated the expression of mammalian target of rapamycin complex 1 (mTORC1), sterol-responsive element-binding protein-1c (SREBP1c), fatty acid synthase (FAS), 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR), and forkhead box protein O1 (FOXO1). SCP significantly increased the protein expression of AKT, GLUT4, AMP-activated protein kinase (AMPK), phosphorylated-AMPK (p-AMPK), phosphorylated-AKT (p-AKT), and uncoupling protein 1 (UCP-1), and decreased the expression of SREBP1c, FAS, HMGCR, phosphorylation of IKBα (p-IKBα), and nuclear factor kappa B subunit p65 (P65) in the liver. Overall, SCP effectively reduced HFD-induced insulin resistance and obesity in mice, partly through NF-
κ
B and IRS/AKT-AMPK signaling pathways to regulate inflammatory factors. Therefore, SCP may improve lifestyle diseases.
The activity and fate of heavy metals (HMs) from mining and smelting activities in farmland soil is of great significance to effectively prevent the excessive enrichment of HMs in crops. This study ...focuses on Baiyin area, a typical mining city in northwest China. In this example, the sources, speciation, and fate of HMs in the farmland soil, and the migration and enrichment characteristics of HMs in the different parts of crops planted in different areas were studied in detail combining the chemical sequential extraction and Pb isotope approaches. Results showed that the mean anthropogenic contributions of HMs in farmland soils were approximately 85%, 88%, 76%, and 41% for the ore district (OD), Xidagou sewage irrigation area (XSIA), Dongdagou sewage irrigation area, and the Yellow River irrigation area, respectively, and the risk that HMs were excessively accumulated in crops in OD and XSIA was high. Compared with soil residual fractions, the isotope ratios 206Pb/207Pb in non-residual fractions (1.1304–1.1669) were closer to the values of local ores, suggesting that anthropogenic HMs from mining and smelting activities were mainly enriched in the non-residual fractions. The isotope ratios 206Pb/207Pb in crops (1.1398–1.1686) further confirmed that those anthropogenic HMs were more easily absorbed and concentrated by crops. HMs contents in leaves from OD and XSIA were generally higher than that in roots, suggesting that atmospheric deposition in OD and XSIA had a greater impact on the HMs concentration of crop leaves，while the excess rate of HMs in grain/fruit was the lowest in all parts of crops. The division and classification of crop planting in mining area can effectively help minimize the risk that HMs from anthropogenic source enter the human body through the food chain.
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•Anthropogenic HMs were mainly enriched in the non-residual fractions of farmland soil.•Soil HMs that from mining and smelting activities can be easily absorb by crops.•Division and classification planting helps minimize the ecological risks of HMs pollution.
Context
ZAP-70 (zeta-chain-associated protein of 70 kDa), serving as a critical regulator for T cell antigen receptor signaling, represents an attractive therapeutic target for autoimmunity disease. ...How the mechanistical mechanism of ZAP-70 to a human autoimmune syndrome-associated R192W mutation remains unclear. The results indicated that the R192W mutation of ZAP-70 clearly affected the conformational flexibility of the N-terminal ITAM-Y2P. Structural analysis unveiled that the R192W mutation of ZAP-70 caused the exposure of the N-terminal ITAM-Y2P to the solvent. MM-GBSA binding free energy calculations exhibited that the R192W mutation decreased the binding affinity of ITAM-Y2P to the ZAP-70 mutant. Residue-based free energy decomposition further revealed that the protein-peptide interaction networks involving electrostatic interactions provide significant contributions for complex formation. The energy unfavorable residues include Arg43, Arg192, Tyr240, and Lys244 from ZAP-70 and Asn301, Leu303, pY304, and pY315 from ITAM-Y2P in the R192W mutant. Our obtained results may help the understanding of the deactivation mechanism of ZAP-70 induced by the R192W mutation.
Methods
In the work, multiple replica molecular dynamics simulations and molecular mechanics-generalized Born surface area (MM-GBSA) method were performed to reveal the doubly phosphorylated ITAMs (ITAM-Y2P)-mediated deactivation mechanism of ZAP-70 induced by the R192W mutation.
The aim of the present study was to investigate the browning effects mechanism of
Smilax china
L. polyphenols (SCLP) and its monomer. In this study, polyphenols (SCLP, engeletin, quercetin and ...caffeic acid) markedly suppressed lipid accumulation. Polyphenols significantly up-graded the expression of protein kinase A (PKA), adipose triglyceride lipase (ATGL), peroxisome proliferators-activated receptors alpha (PPARα), carnitine palmitoyl transferase (CPT) and acyl-CoA oxidase (ACO) to promote lipolysis and
β
-oxidation. Moreover, polyphenols greatly enhanced mitochondrial biogenesis in adipocytes, as demonstrated by the expression of
Nrf1
and
Tfam
were up-regulated. Furthermore, polyphenols treatment greatly up-regulated the browning program in adipocytes by increased brown-specific genes and proteins uncoupling protein 1 (UCP-1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1
α
) and PR domain containing 16 (PRDM16), as well as beige-specific genes (
Tmem26
,
Tbx1
,
CD137
,
Cited1
), especially engeletin. Further research found that the brown-specific markers were decreased by antagonist treatment of AMPK or
β
3-AR, but polyphenols treatment reversed the effect of antagonists and improved the expression of UCP-1, PRDM16 and PGC-1
α
. In conclusion, these results indicated that polyphenols stimulate browning in adipocytes via activation of the
β
3-AR/AMPK signaling pathway, and SCLP and its monomer may be worth investigating to prevent obesity.
The aim of this work was to investigate the xanthine oxidase (XO)-inhibitory activity of ethanol extracts from
L. and to identify the active compounds in the ethyl acetate (EtOAc) fraction. ...Extraction of ethanol extracts from
L. and then ethanol extracts were concentrated, and the polyphenolic compounds were extracted with petroleum ether (PE), chloroform, EtOAc, n-butanol (n-BuOH), and residual ethanol fractions. Their effects on XO activity were then compared separately. The polyphenolic components of the EtOAc fraction were identified by HPLC and HPLC-mass spectrometry (HPLC-MS) analysis. Kinetic analysis demonstrated that all these extracts showed XO-inhibitory properties, and among them the EtOAc fraction had the strongest inhibitory effect (IC
= 101.04 μg/mL). The inhibitory constant (
) of the EtOAc fraction on XO activity was 65.20 μg/mL, showing excellent inhibition on XO in the competitive mode. Sixteen compounds were identified from the EtOAc fraction. The study demonstrates that the EtOAc fraction of
L. may be a potential functional food to inhibit XO activity.
Hydrocarbon-rich natural gases from the Tarim, Junggar, Turpan-Hami and Santanghu basins in Xinjiang, Northwest China have measured 3He/4He ratios from 0.01 to 0.6 times higher than the atmospheric ...value, indicating 0–7% helium derived from the mantle. The mantle-derived helium is high in foreland basins associated with the Tianshan, Kunlun and Zhayier-Halalate orogenic mountains, but low towards the center of basins. This spatial distribution suggests that the mantle-derived helium originates either from fluids or small scale melts in the upper asthenospheric or lithospheric mantle which have found pathways into the root zones of the major faults defining these mountains, but do not significantly move into the basins themselves. During upward transport to near the surface, the mantle-derived helium is significantly diluted by radiogenic helium produced in the crust. Despite the lack of recent magmatic activity or extensional tectonics within the basins, this pattern shows strong evidence that the major faults play an important role in mantle-derived components degassing from the mantle to the surface.
•We have measured 3He/4He of natural gases in 5 sedimentary basins in Xinjiang, NW China.•As much as approximately 7% of the helium in the Xinjiang basins is mantle-derived.•Mantle-derived helium in foreland sub-basins reflects the injection of mantle fluids beneath the orogenic mountains through thrust faults.•Purely radiogenic helium occurs extensively in the center of individual sedimentary basins.•The possible mantle-derived CO2 in Tarim basin is proposed.
In order to investigate the mechanisms by which puerarin from kudzu root extract regulates lipid metabolism, fifty mice were randomly assigned to five groups: normal diet, high-fat diet (HFD), and ...HFD containing 0.2%, 0.4% or 0.8% puerarin for 12 weeks. Body weight, intraperitioneal adipose tissue (IPAT) weight, serum biochemical parameters, and hepatic and feces lipids were measured. Activity and mRNA and protein expressions of hepatic lipid metabolism-related enzymes were analyzed. Compared with HFD, 0.4% and 0.8% puerarin significantly decreased body and IPAT weight. There was a significant decrease in the serum and hepatic concentrations of total cholesterol, triglycerides and leptin in mice fed the 0.4% and 0.8% puerarin diets compared with HFD. Fatty acid synthase activity was suppressed in mice fed the 0.4% and 0.8% puerarin diets, while the activities of AMP-activated protein kinase (AMPK), carnitine acyltransferase (CAT) and hormone-sensitive lipase (HSL) were increased. mRNA expression of peroxisome proliferator-activated receptor γ 2 (PPARγ 2) was down-regulated in liver of mice fed the 0.8% diet compared with HFD, while mRNA expression of CAT and HSL was considerably up-regulated by 0.4% and 0.8% puerarin diets. The protein expression of PPARγ2 in liver was decreased and those of p-AMPK, HSL and p-HSL were increased in mice fed 0.4% and 0.8% puerarin diets. These results suggest that > 0.4% puerarin influenced the activity, mRNA and protein levels of hepatic lipid metabolism-related enzymes, decreasing serum and liver lipids, body weight gain and fat accumulation. Puerarin might be beneficial to prevent lifestyle-related diseases.
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