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1.
Sci Total Environ ; 945: 174093, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38906307

ABSTRACT

Black carbon (BC) and brown carbon (BrC) over the high-altitude Tibetan Plateau (TP) can significantly influence regional and global climate change as well as glacial melting. However, obtaining plateau-scale in situ observations is challenging due to its high altitude. By integrating reanalysis data with on-site measurements, the spatial distribution of BC and BrC can be accurately estimated using the random forest algorithm (RF). In our study, the on-site observations of BC and BrC were successively conducted at four sites from 2018 to 2021. Ground-level BC and BrC concentrations were then obtained at a spatial resolution of 0.25° × 0.25° for three periods (including Periods-1980, 2000, and 2020) using RF and multi-source data. The highest annual concentrations of BC (1363.9 ± 338.7 ng/m3) and BrC (372.1 ± 96.2 ng/m3) were observed during Period-2000. BC contributed a dominant proportion of carbonaceous aerosol, with concentrations 3-4 times higher than those of BrC across the three periods. The ratios of BrC to BC decreased from Period-1980 to Period-2020, indicating the increasing importance of BC over the TP. Spatial distributions of plateau-scale BC and BrC concentrations showed heightened levels in the southeastern TP, particularly during Period-2000. These findings significantly enhance our understanding of the spatio-temporal distribution of light-absorbing carbonaceous aerosol over the TP.

2.
Article in English | MEDLINE | ID: mdl-38916408

ABSTRACT

With the continuous development of wearable electronics, higher requirements are put forward for flexible, detachable, stable output, and long service life power modules. Given the limited capacity of energy storage devices, the integration of energy capture and storage is a viable approach. Here, we present a flexible, wearable, wireless-charging power system that integrates a piezoelectric ultrasonic array harvester (PUAH) with MXene-based solid-state supercapacitors (MSSSs) in a soft wristband format for sustainable applications. The MSSS as the energy storage module is developed by using Ti3C2Tx nanosheet-loaded inserted finger-like carbon cloth skeletons as electrodes and poly(vinyl alcohol)/H3PO4 gel as electrolytes, with high energy density (58.74 Wh kg-1) and long cycle life (99.37%, 10,000 cycles). A two-dimensional stretchable piezoelectric array as a wireless-charging module hybridizes high-performance 1-3 composite units with serpentine electrodes, which allows wireless power via ultrasonic waves, with a maximum power density of 1.56 W cm-2 and an output voltage of 20.75 V. The overall PUAH-MSSS wireless energy supply system is 2 mm thick and offers excellent energy conversion/storage performance, cyclic stability, and mechanical flexibility. The results of this project will lay the foundation for the development of next-generation wearable electronics.

3.
Org Lett ; 26(13): 2606-2611, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38513116

ABSTRACT

Enesulfinamides with α,ß,ß-trisubstitution undergo a Simmons-Smith reaction to yield multisubstituted cyclopropylamine derivatives with high stereocontrol. The resulting α-tertiary cyclopropylamine derivatives, which feature ß-quaternary stereocenters bearing two electronically and sterically similar substituents (e.g., methyl and ethyl), are seldom achieved by using conventional methods. By adjusting the stereochemistry of the carbon-carbon double bond and/or sulfinyl group within the enesulfinamides, it is feasible to selectively produce four stereoisomers of the cyclopropylamines, each with different absolute configurations at the α- and ß-carbons.

4.
Small ; 20(8): e2306111, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37821411

ABSTRACT

Aqueous zinc ion battery (AZIBs) has attracted the attention of many researchers because of its safety, economy, environmental protection, and high ionic conductivity of electrolytes. However, the battery greatly suffers from zinc dendrite produced by zinc metal anode leading to poor cycle life and even unsafe problems, which limit its further development for various important applications. It is known that the success of the commercialization of lithium-ion batteries (LIBs) is mainly due to replacement of lithium metal anode with graphite, which avoids the formation of Li dendrite. Therefore, it is an important step to develop aqueous zinc ion anode to replace conventional zinc metal one with zinc-metal free anode material. In this review, the working principle and development prospect of "rocking-chair" AZIBs are introduced. The research progress of different types of zinc metal-free anode materials and cathode materials in "rocking-chair" AZIBs is reviewed. Finally, the limitations and challenges of the Zn metal-free "rocking-chair" AZIBs as well as solutions are deeply discussed, aiming to provide new strategies for the development of advanced zinc-ion batteries.

5.
iScience ; 26(12): 108467, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38089590

ABSTRACT

Accurate risk stratification for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is crucial for prognosis and treatment decisions. Here, we develop a tumor microenvironment-associated circular RNA (circRNA) signature that can stratify LA-NPC patients with different risks of relapse and vulnerability to induction chemotherapy (IC). Relapsed-related circRNAs are identified by comparing expression profiles between patients with and without relapse, followed by quantitative validation in the training cohort (n = 170). A nine-circRNA signature is constructed to classify patients into high-risk and low-risk groups. Low-risk patients have significantly favorable clinical survivals, which is validated in the internal (n = 170) and external (n = 150) cohorts. They are characterized by an immune-active microenvironment and can derive benefits from IC. Meanwhile, high-risk patients characterized with pro-relapse and DNA repair-associated features, are vulnerable to chemoresistance. Overall, the circRNA-based classifier serves as a reliable prognostic tool and might guide chemotherapy decisions for patients with LA-NPC.

6.
Huan Jing Ke Xue ; 44(11): 6279-6286, 2023 Nov 08.
Article in Chinese | MEDLINE | ID: mdl-37973110

ABSTRACT

To explore the occurrence characteristics and influencing factors of microplastics in soil in the Danjiangkou Reservoir area, this study collected soil samples from orchards, dryland, paddy fields, and wetland and identified microplastics in soil via density sorting, microscope observation, and Raman spectrometry. The results showed that microplastics were detected in 64 samples collected in the study area, and the abundance ranged from 645 to 15161 n·kg-1. The spatial distribution of microplastics in the bottom of the reservoir was higher than those in the middle and head of the reservoir, and the abundance of microplastics in the surface soil(0-20 cm) was significantly lower than that in the bottom soil(20-40 cm). The main types of microplastics were polypropylene(26.4%) and polyamide(20.2%), the particle size was mainly concentrated between 50-500 µm(75%), and the common shape was fragments(66.2%). Correlation analysis showed that soil microplastic abundance was closely related to land use, distance from water and housing, population density, and soil properties. From the perspective of microplastic pollution risk, 72.1% of the region's microplastic polymer risk index was at level Ⅲ and level Ⅳ, and there was a certain risk of microplastic pollution in the Danjiangkou Reservoir area. The results of this study can provide support for risk assessment of microplastics.

7.
Huan Jing Ke Xue ; 44(10): 5382-5391, 2023 Oct 08.
Article in Chinese | MEDLINE | ID: mdl-37827756

ABSTRACT

Air pollution continues to be a serious problem in Xi'an. A heavy pollution process and formation mechanism were investigated in Xi'an in January 2019 using multi-source methods (such as material balance and sulfur/nitrogen oxidation rate (SOR/NOR)). The multi-source data included the concentrations of PM2.5, PM10, SO2, NO2, CO, and O3; the chemical components of PM2.5; the meteorological records of ground and vertical observations; the atmospheric reanalysis data. Three phases were obtained including the accumulation phase (P1), maintenance phase (P2), and dispersion phase (P3) during the pollution period. The pollution event was primarily attributed to the superposition of adverse weather conditions and feedback effects. During the periods of P1 and P2, the area of Xi'an was affected by blocking and zonal westerly airflow at 500 hPa (with flat westerly airflow) and uniform-distribution pressure at sea level with a limited pressure gradient and stable weather conditions, and the easterly wind was dominant at 925 hPa; not all of these factors were conducive to the pollutant diffusion. An interaction feedback mechanism between meteorological conditions and heavy pollution could be studied using the ground-based microwave radiometer. The correlations between PM2.5 and inversions of water vapor density, relative humidity, air temperature, and temperature inversion were significant with coefficients of 0.86, 0.62, 0.53, and 0.38, respectively. The feedback mechanism was primarily manifested as follows:with the pollutant accumulation, the radiative cooling effect could lead to or strengthen the occurrence and intensity of temperature inversion, decrease the mixed layer height, and cause moisture accumulation. High humidity could further maintain the pollution by accelerating the secondary formation and promoting the hygroscopic growth of aerosol particles. Therefore, the dominant chemical components to PM2.5were secondary inorganic ions (SO42-+NO3-+NH4+, SNA) and "other" components during the period of P2, with contributions of 43.2% and 23.1%, respectively. In addition, the peak values of PM2.5, SOR, NOR, and the light extinction coefficients all occurred on the same days (January 3 and 6), indicating that the effect of secondary formation was important for both heavy pollution events and visibility. The total contribution of NH4NO3, organic matter (OM), (NH4)2SO4, and EC to the light extinction coefficient was more than 85%. Limited variations in the proportion for components were observed in three phases. During the period of P3, the strong cold air in the mid-lower atmosphere was conducive to the dry and clean air sinking and the pressure gradient at sea level increasing. These were beneficial to the diffusion of air pollutants and water vapor.

8.
Org Lett ; 25(29): 5536-5541, 2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37458358

ABSTRACT

In the presence of boron trifluoride, conjugate addition of organocuprates to α-substituted α,ß-unsaturated N-tert-butanesulfinyl ketimines provides facile access to acyclic ß,ß-disubstituted enesulfinamides with high ratios of geometric isomers. Diverse and challenging to synthesize, multisubstituted aza-enolates bearing two electronically and sterically similar ß-substituents, which are important precursors for asymmetric construction of the less accessible acyclic quaternary or tetrasubstituted stereocenters at the α-position of ketimines, can be efficiently prepared in good yields with high stereocontrol.

9.
Front Endocrinol (Lausanne) ; 14: 1170727, 2023.
Article in English | MEDLINE | ID: mdl-37465128

ABSTRACT

Introduction: Many patients who undergo assisted reproductive technology (ART) suffer from recurrent implantation failure (RIF). The addition of hyaluronic acid (HA) to the transfer medium is one of several methods to improve pregnancy outcomes. We investigated whether HA could improve the live birth and clinical pregnancy rates of RIF patients. Methods: This study included 248 RIF patients, who were divided into two groups: the control (CTL) group (n=137), which received transfer medium without HA, and the HA group (n=111), which received transfer medium with HA. The two groups were compared according to the ART outcome. Results: The primary outcomes were the clinical pregnancy and live birth rates. Secondary outcomes include a positive urine pregnancy test, the implantation, ongoing pregnancy, multiple pregnancy, clinical miscarriage, and ectopic pregnancy rates, foetal or congenital defects, obstetric complications, infant birth weight and any related adverse events. Regarding the primary outcomes, the clinical pregnancy rate was significantly higher in the HA group than in the control group, and there was no significant difference in the live birth rate (LBR) between the HA and control groups. Regarding the secondary outcomes, the implantation, multiple pregnancy and ectopic pregnancy rates were similar between the two groups. Discussion: Our findings supported the conclusion that HA can improve the clinical pregnancy rate of patients with RIF undergoing FET cycles, but the live birth rate was not significantly improved with the addition of HA to the traditional transfer medium.


Subject(s)
Hyaluronic Acid , Pregnancy, Ectopic , Female , Pregnancy , Humans , Retrospective Studies , Hyaluronic Acid/pharmacology , Embryo Transfer/methods , Embryo Implantation
10.
Small ; 19(35): e2300467, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37127871

ABSTRACT

Ni(OH)2 nanosheet, acting as a potential active material for supercapacitors, commonly suffers from sluggish reaction kinetics and low intrinsic conductivity, which results in suboptimal energy density and long cycle life. Herein, a convenient electrochemical halogen functionalization strategy is applied for the preparation of mono/bihalogen engineered Ni(OH)2 electrode materials. The theoretical calculations and experimental results found that thanks to the extraordinarily high electronegativity, optimal reversibility, electronic conductivity, and reaction kinetics could be achieved through F functionalization . However, benefiting from the largest ionic radius, INi(OH)2 contributes the best specific capacity and morphology transformation, which is a new finding that distinguishes it from previous reports in the literature. The exploration of the interaction effect of halogens (F, INi(OH)2 , F, BrNi(OH)2 , and Cl, INi(OH)2 ) manifests that F, INi(OH)2 delivers a higher specific capacity of 200.6 mAh g-1 and an excellent rate capability of 58.2% due to the weaker electrostatic repulsion, abundant defect structure, and large layer spacing. Moreover, the F, INi(OH)2 //FeOOH@NrGO device achieves a high energy density of 97.4 Wh kg-1 and an extremely high power density of 32426.7 W kg-1 , as well as good cycling stability. This work develops a pioneering tactic for designing energy storage materials to meet various demands.

11.
Org Lett ; 24(48): 8925-8929, 2022 12 09.
Article in English | MEDLINE | ID: mdl-36445047

ABSTRACT

A single-flask cascade of Michael addition and Wittig olefination was developed to allow the stereoselective α-allylic alkylation of α-branched N-tert-butanesulfinyl ketimines for the construction of acyclic quaternary stereocenters bearing two sterically and electronically similar substituents. In this process, tBuOK-promoted stereoselective α-deprotonation gives fully substituted aza-enolates with a stereodefined geometry, Michael addition with α,ß-unsaturated phosphonates generates C-C bonds with exceptional stereocontrol, and finally paraformaldehyde trapping of the conjugate addition intermediate generates functionalized α-allylated imines.

12.
Sci Total Environ ; 848: 157814, 2022 Nov 20.
Article in English | MEDLINE | ID: mdl-35931170

ABSTRACT

Atmospheric black carbon (BC), primary and secondary brown carbon (BrCpri and BrCsec) are the light-absorbing carbonaceous aerosol components. The vertical changes in the BC and BrC distributions are not generally known. Here, we presented a study of the spectral light absorption properties, direct solar absorption, and potential source areas of BC and BrC at the foothill (375 m a.s.l.) and summit (2060 m a.s.l.) of Mt. Hua, China. More than tripled BC and BrC light absorption coefficient were observed at the foothill compared to the summit. The dominant carbonaceous light-absorbing was attributed to BC with the percentages of 77 % (foothill) and 79 % (summit), respectively. The light absorption coefficient and direct solar absorption of BrCpri were much higher than those of BrCsec at foothill, especially in winter. The enhancing contributions of BrCsec light absorption coefficient and direct solar absorption were observed with high RH and visibility at the summit. The light absorption properties of BC, BrCpri, and BrCsec may be attributed to the emissions, meteorological conditions, and photochemical oxidation. The inferred potential source spatial distributions of BC and BrCpri showed different patterns at the foothill and summit. The results underlined the primary emission effects (including BC and BrCpri) at the foothill and the importance of BrCsec at the summit, respectively.


Subject(s)
Air Pollutants , Carbon , Aerosols/analysis , Air Pollutants/analysis , Carbon/analysis , China , Environmental Monitoring/methods , Soot/analysis
13.
Org Lett ; 24(15): 2883-2888, 2022 04 22.
Article in English | MEDLINE | ID: mdl-35420435

ABSTRACT

A Mannich reaction of deprotonated, highly enantioenriched α,α-disubstituted N-tert-butanesulfinyl ketimines with isatin-derived ketimines was developed to prepare 3-amino-3-substituted oxindoles bearing an acyclic quaternary stereogenic carbon substituted with two sterically similar groups. The excellent stereocontrol of the deprotonation enabled the formation of metalloenamine intermediates with stereodefined geometry, while the precise facial selectivity of the C-C bond formation allowed the construction of contiguous quaternary and tetrasubstituted stereocenters with excellent stereoselectivity.


Subject(s)
Isatin , Carbon/chemistry , Catalysis , Isatin/chemistry , Oxindoles , Stereoisomerism
14.
Zhongguo Zhong Yao Za Zhi ; 47(23): 6466-6475, 2022 Dec.
Article in Chinese | MEDLINE | ID: mdl-36604893

ABSTRACT

The present study aimed to explore the targets and mechanism of Mailuo Shutong Pills(MSP) in the treatment of ischemic stroke by network pharmacology, and verify the key targets through molecular docking and animal experiment, so as to provide a theoretical basis for the clinical application of MSP. The main chemical ingredients of MSP were obtained by searching against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and relevant literature. The potential targets of the ingredients of MSP in treating ischemic stroke were obtained from SwissTargetPrediction and DisGeNET. Protein-protein interaction(PPI) network was analyzed in STRING and plotted in Cytoscape. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were carried out with DAVID. Molecular docking was simulated to determine the binding activity of active ingredients to key targets in AutoDock Vina. The mouse model of ischemic stroke was established. The mice were classified into a sham group, a model group, and an MSP group. After the administration, cerebral infarction volume was detected by 2,3,5-triphenyltetrazoliumchloride(TTC) staining, and Western blot was performed to determine the levels of phosphatidylinositol 3-kinase(PI3 K), protein kinase B(AKT), nuclear factor-κB(NF-κB) and their phosphorylated proteins. A total of 222 ingredients of MSP were screened out, including beta-sitosterol, quercetin, licochalcone B, and lupiwighteone, which acted on 701 targets. Totally 1 079 targets associated with ischemic stroke were retrieved, among which 192 common targets were shared by MSP and ischemic stroke. The key targets included AKT1, phosphatidylinositol 3-kinase catalytic subunit alpha(PIK3 CA), phosphatidylinositol 3-kinase regulatory subunit 1(PIK3 R1), and nuclear factor-κB p65 subunit(RELA), which were mainly involved in PI3 K/AKT, tumor necrosis factor(TNF), and NF-κB signaling pathways. The results of molecular docking revealed that PI3 K, AKT1, and RELA had good binding ability to the active ingredients of MSP. The animal experiment results showed that compared with the model group, MSP decreased cerebral infarction volume, down-regulated the expression of p-NF-κB, and up-regulated the expression of p-PI3 K and p-AKT in mouse brain. In summary, the active ingredients in MSP may treat cerebral injury by activating PI3 K/AKT signaling pathway and inhibiting NF-κB signaling pathway.


Subject(s)
Drugs, Chinese Herbal , Ischemic Stroke , Animals , Mice , NF-kappa B/genetics , Proto-Oncogene Proteins c-akt/genetics , Ischemic Stroke/drug therapy , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases/genetics , Cerebral Infarction , Drugs, Chinese Herbal/pharmacology
15.
ACS Appl Mater Interfaces ; 13(19): 23230-23238, 2021 May 19.
Article in English | MEDLINE | ID: mdl-33970595

ABSTRACT

As a typical transition-metal dichalcogenides, vanadium diselenide (VSe2) is a promising electrode material for aqueous zinc-ion batteries due to its metallic characteristics and excellent electronic conductivity. In this work, we propose a strategy of hydrothermal reduction synthesis of stainless-steel (SS)-supported VSe2 nanosheets with defect (VSe2-x-SS), thereby further improving the conductivity and activity of VSe2-x-SS. Density functional theory calculations confirmed that Se defect can adjust the adsorption energy of Zn2+ ions. This means that the adsorption/desorption process of Zn2+ ions on VSe2-x-SS is more reversible than that on pure SS-supported VSe2 (VSe2-SS). As a result, the Zn//VSe2-x-SS battery showed more excellent electrochemical performance than Zn//VSe2-SS. The VSe2-x-SS electrode shows a good specific capacity of 265.2 mA h g-1 (0.2 A g-1 after 150 cycles), satisfactory rate performance, and impressive cyclic stability. In addition, we also have explored the energy-storage mechanism of Zn2+ ions in this VSe2-x-SS electrode material. This study provides an effective strategy for the rational design of electrode materials for electrochemical energy-storage devices.

16.
Sci Rep ; 11(1): 9194, 2021 04 28.
Article in English | MEDLINE | ID: mdl-33911133

ABSTRACT

The effects of high potassium and normal potassium treatments on protein expression in roots of flue-cured tobacco plant HKDN-5 at the seedling stage were analyzed by an unlabeled protein quantification technique. The results showed that 555 proteins were differentially expressed (245 proteins were down-regulated and 310 proteins were up-regulated) in high potassium treatment compared with normal potassium treatment. Differentially expressed proteins were involved in 96 metabolic pathways (42 metabolic pathways, 21 synthetic pathways as well as catabolic pathways, including fatty acid metabolism, phenylpropane biosynthesis, ketone body synthesis and degradation, and butyric acid metabolism. Root processing of high potassium concentrations leads to increases in the synthesis of peroxidase, superoxide dismutase and acyl-coenzyme-A synthetase. Additional proteomic differences observed in tobacco roots grown in high potassium include proteins involved with genetic information processing as well as environmental sensing. Examples include RNA helicase, ABC transporters and large subunit GTPases. These up-regulated differentially expressed proteins function mainly in protein translation, ribosome structure and protein synthesis. This indicates that under high potassium treatment, root protein synthetic processes are accelerated and substance metabolism pathways are enhanced; thus, providing the material and energetic basis for root growth.


Subject(s)
Nicotiana/metabolism , Plant Proteins/metabolism , Plant Roots/metabolism , Potassium/pharmacology , Proteome/drug effects , Seedlings/metabolism , Plant Roots/drug effects , Plant Roots/growth & development , Seedlings/drug effects , Seedlings/growth & development , Stress, Physiological , Nicotiana/drug effects , Nicotiana/growth & development
17.
Zhongguo Zhong Yao Za Zhi ; 46(2): 388-390, 2021 Jan.
Article in Chinese | MEDLINE | ID: mdl-33645126

ABSTRACT

Two phloroglucinol compounds(1-2) were isolated and purified from 95% ethanol extract of Dryopteris fragrans through various column chromatographies on silica gel, Sephadex LH-20, medium pressure column chromatography, and preparative HPLC. Their structures were elucidated as 2',4',6'-trihydroxy-5'-methyl acetate-3'-methyl-1'-butyrophenone(1) and aspidinol B(2) based on their chemical and physicochemical methods and spectroscopic data. Compound 1 is a new phloroglucinol compound named "dryofraginol".


Subject(s)
Dryopteris , Chromatography, High Pressure Liquid , Ethanol , Phloroglucinol , Plant Extracts
18.
Horm Metab Res ; 52(7): 532-539, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32375182

ABSTRACT

Although glucagon-like peptide-1 (GLP-1) analogue has been reported to suppress oxidative stress in non-alcoholic fatty liver disease (NAFLD), an effective therapeutic agent for NAFLD is currently unavailable. Therefore, in this study, we aimed to investigate the protective effects of the GLP-1 analogue liraglutide against lipotoxicity-induced oxidative stress in HepG2 cells and to elucidate the underlying mechanisms. HepG2 cells were cultured for 48 hours and treated with a free fatty acid (FFA) mixture: FFA mixture and liraglutide or FFA mixture, liraglutide, and exendin (9-39). Lipid accumulation was examined by oil red O staining. Oxidative stress was assessed by measuring the levels of intracellular reactive oxygen species using 2',7'-dichlorofluorescein diacetate and thiobarbituric acid-reactive substances, whereas antioxidant capacity was assessed by measuring the activity of superoxide dismutase and catalase. Expression of the nuclear factor erythroid-2-related factor 2 (NRF2) gene and the genes encoding antioxidant enzymes was analyzed using quantitative RT-PCR. Cellular and nuclear NRF2 expression levels were assessed using immunofluorescence cell staining and western blotting. Liraglutide treatment reduced high fat-induced lipid formation and the levels of oxidative stress markers and increased antioxidant enzyme activity in HepG2 cells. Liraglutide treatment increased the mRNA expression of NRF2 target genes, induced NRF2 nuclear translocation, and increased nuclear NRF2 levels without altering NRF2 mRNA expression. Collectively, these results indicate that liraglutide exhibits a protective effect against lipotoxicity-induced oxidative stress, possibly via modulation of NRF2 and expression of antioxidant enzymes in liver cells.


Subject(s)
Fatty Acids, Nonesterified/toxicity , Liraglutide/pharmacology , Liver/drug effects , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/prevention & control , Cytoprotection/drug effects , Hep G2 Cells , Humans , Lipid Droplets/drug effects , Lipid Droplets/metabolism , Liver/metabolism , NF-E2-Related Factor 2/physiology , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/prevention & control , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Thiobarbituric Acid Reactive Substances/metabolism
19.
Sarcoma ; 2020: 3498549, 2020.
Article in English | MEDLINE | ID: mdl-33488267

ABSTRACT

Advances in molecular diagnostics have identified subsets of Ewing and Ewing-like sarcomas driven by variant translocations with unique biology. It is likely that patients with these tumours will have different clinical features and therapeutic outcomes. Nevertheless, the management of these patients both locally and within cooperative group trials depends on the local pathological diagnosis. It is not known what molecular diagnostic approaches are employed by local pathologists or if the exact translocation is commonly determined. In addition, it is not known what therapeutic approaches are employed for these patients or what cooperative trials are deemed appropriate for these patients by expert consensus. To answer these questions, we performed an international survey of oncologists and pathologists to better understand the diagnostic approaches used to identify variant translocations and the influence the findings have on therapy and clinical trial eligibility. An online survey was distributed to oncologists and pathologists primarily in North America. A total of 141 surveys were completed, representing a 28% response rate. The majority of respondents considered EWSR1-ETS gene family translocations (range 61-96%) to be Ewing sarcoma and would include them on the primary arm of a Ewing sarcoma clinical trial. There was a lack of consensus on how to classify and stratify BCOR-CCNB3, CIC-DUX4, and EWSR1+ with non-ETS partner fusions. Most respondents were either unsure how their institution tested, or their institution did not perform the test. In cases with atypical Ewing morphology, most respondents favoured additional fusion transcript testing. There is a lack of consensus regarding the classification and stratification of rare molecular subtypes in Ewing sarcoma. It is not clear how these alternative translocations have impacted outcomes for past clinical studies. This suggests a need for molecular confirmation of diagnoses and centralized or minimum standardization of testing for future trial enrolment.

20.
Oncogene ; 38(21): 4028-4046, 2019 05.
Article in English | MEDLINE | ID: mdl-30692632

ABSTRACT

The nuclear factor E2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling cascades is a key transcriptional pathway governing cellular oxidative stress and tumor development. Mammalian hepatitis B X-interacting protein (HBXIP) has critical roles in modulating cancer malignance and tumor progression. However, whether HBXIP interacts with KEAP1 and NRF2 is unclear. Here, we found that HBXIP can effectually compete with NRF2 for binding with KEAP1 protein via its highly conserved GLNLG motif. The HBXIP-mediated reduction in NRF2-KEAP1 complexes promotes NRF2 accumulation and nuclear entry, which facilities the activation of antioxidant response element (ARE)-dependent signaling cascades, thereby reducing the accumulation of endogenous cellular reactive oxygen species (ROS). We also found a strong positive correlation between HBXIP expression and NRF2 expression in breast cancer cells, tissue microarrays and clinical breast cancer tissues. Furthermore, this positive correlation was further confirmed via analysis of 1905 clinical cases of breast carcinoma provided by the cancer genomics database cBioPortal. Strikingly, disrupting the HBXIP-KEAP1 axis via mutating the GLNLG motif of HBXIP leads to potent inhibition of the malignancy of breast carcinoma both in vivo and in vitro. Our findings broaden our understanding of HBXIP as a modulation factor of cellular oxidative stress and address a novel regulatory mechanism governing redox homeostasis and the progression of breast carcinoma.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Proliferation/physiology , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , Neoplasm Metastasis/pathology , Animals , Antioxidant Response Elements/physiology , Cell Line, Tumor , Cell Nucleus/metabolism , Female , HEK293 Cells , Humans , MCF-7 Cells , Mice, Inbred BALB C , Oncogene Proteins/metabolism , Oxidative Stress/physiology , Protein Binding/physiology , Reactive Oxygen Species/metabolism , Signal Transduction/physiology
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