Publications by authors named "Gui-Zhen Wang"

38 Publications

Comprehensive analysis of BTN3A1 in cancers: mining of omics data and validation in patient samples and cellular models.

FEBS Open Bio 2021 Sep 4;11(9):2586-2599. Epub 2021 Aug 4.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Butyrophilin 3A1 (BTN3A1), a major histocompatibility complex-associated gene that encodes a membrane protein with two extracellular immunoglobulin domains and an intracellular B30.2 domain, is critical in T-cell activation and adaptive immune response. Here, the expression of BTN3A1 in cancers was analyzed in eight databases comprising 86 733 patients of 33 cancers, and the findings were validated in patient samples and cell models. We showed that BTN3A1 was expressed in most cancers, and its expression level was strongly correlated with clinical outcome of 13 cancers. Mutations of BTN3A1 were detected, and the mutations were distributed throughout the entire gene. Gene set enrichment analysis showed that BTN3A1 co-expression genes and interacting proteins were enriched in immune regulation-related pathways. BTN3A1 was associated with tumor-infiltrating immune cells and was co-expressed with multiple immune checkpoints in patients with breast cancer (BRCA) and non-small cell lung cancer (NSCLC). We reported that BTN3A1 was downregulated in 46 of 65 (70.8%) NSCLCs, and its expression level was inversely associated with clinical outcome of the patients. BTN3A1 in tumor samples was lower than in counterpart normal tissues in 31 of 38 (81.6%) BRCAs. Bioinformatics analyses showed that BTN3A1 could be a target gene of transcription factor Spi-1 proto-oncogene (SPI1), and our 'wet' experiments showed that ectopic expression of SPI1 upregulated, whereas silencing of SPI1 downregulated, BTN3A1 expression in cells. These results suggest that BTN3A1 may function as a tumor suppressor and may serve as a potential prognostic biomarker in NSCLCs and BRCAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/2211-5463.13256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409294PMC
September 2021

CXCL13 Signaling in the Tumor Microenvironment.

Adv Exp Med Biol 2021 ;1302:71-90

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Chemokines have emerged as important players in tumorigenic process. An extensive body of literature generated over the last two or three decades strongly implicate abnormally activated or functionally disrupted chemokine signaling in liaising most-if not all-hallmark processes of cancer. It is well-known that chemokine signaling networks within the tumor microenvironment are highly versatile and context-dependent: exert both pro-tumoral and antitumoral activities. The C-X-C motif chemokine ligand 13 (CXCL13), and its cognate receptor CXCR5, represents an emerging example of chemokine signaling axes, which express the ability to modulate tumor growth and progression in either way. Collateral evidence indicate that CXCL13-CXCR5 axis may directly modulate tumor growth by inducing proliferation of cancer cells, as well as promoting invasive phenotypes and preventing their apoptosis. In addition, CXCL13-CXCR5 axis may also indirectly modulate tumor growth by regulating noncancerous cells, particularly the immune cells, within the tumor microenvironment. Here, we review the role of CXCL13, together with CXCR5, in the human tumor microenvironment. We first elaborate their patterns of expression, regulation, and biological functions in normal physiology. We then consider how their aberrant activity, as a result of differential overexpression or co-expression, may directly or indirectly modulate the growth of tumors through effects on both cancerous and noncancerous cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-030-62658-7_6DOI Listing
July 2021

Upregulation of wild-type p53 by small molecule-induced elevation of NQO1 in non-small cell lung cancer cells.

Acta Pharmacol Sin 2021 May 25. Epub 2021 May 25.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.

The tumor suppressor p53 is usually inactivated by somatic mutations in malignant neoplasms, and its reactivation represents an attractive therapeutic strategy for cancers. Here, we reported that a new quinolone compound RYL-687 significantly inhibited non-small cell lung cancer (NSCLC) cells which express wild type (wt) p53, in contract to its much weaker cytotoxicity on cells with mutant p53. RYL-687 upregulated p53 in cells with wt but not mutant p53, and ectopic expression of wt p53 significantly enhanced the anti-NSCLC activity of this compound. RYL-687 induced production of reactive oxygen species (ROS) and upregulation of Nrf2, leading to an elevation of the NAD(P)H:quinoneoxidoreductase-1 (NQO1) that can protect p53 by inhibiting its degradation by 20S proteasome. RYL-687 bound NQO1, facilitating the physical interaction between NQO1 and p53. NQO1 was required for RYL-687-induced p53 accumulation, because silencing of NQO1 by specific siRNA or an NQO1 inhibitor uridine, drastically suppressed RYL-687-induced p53 upregulation. Moreover, a RYL-687-related prodrug significantly inhibited tumor growth in NOD-SCID mice inoculated with NSCLC cells and in a wt p53-NSCLC patient-derived xenograft mouse model. These data indicate that targeting NQO1 is a rational strategy to reactivate p53, and RYL-687 as a p53 stabilizer bears therapeutic potentials in NSCLCs with wt p53.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41401-021-00691-8DOI Listing
May 2021

Suppression of Musashi‑2 by the small compound largazole exerts inhibitory effects on malignant cells.

Int J Oncol 2020 05 19;56(5):1274-1283. Epub 2020 Feb 19.

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.

RNA‑binding protein Musashi‑2 (MSI2) serves as a regulator of numerous pivotal biological processes associated with cancer initiation, development and resistance to treatment, and may represent a promising drug target. However, whether MSI2 inhibition is of value in antitumor treatment remains to be determined. The present study demonstrated that MSI2 was upregulated in non‑small cell lung cancer (NSCLC) and was inversely associated with the clinical outcome of the patients. Molecular docking analysis demonstrated that the small compound largazole binds to and may be a potential inhibitor of MSI2. Largazole markedly decreased the protein and mRNA levels of MSI2 and suppressed its downstream mammalian target of rapamycin signaling pathway. Largazole also inhibited the proliferation and induced apoptosis of NSCLC and chronic myeloid leukemia (CML) cells (including bone marrow mononuclear cells harvested from CML patients). These results indicate that MSI2 is an emerging therapeutic target for NSCLC and CML, and the MSI2 inhibitor largazole may hold promise as a treatment for these malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijo.2020.4993DOI Listing
May 2020

Systematic identification of CDC34 that functions to stabilize EGFR and promote lung carcinogenesis.

EBioMedicine 2020 Mar 27;53:102689. Epub 2020 Feb 27.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

Background: How the oncoprotein epidermal growth factor receptor (EGFR) evades proteolytic degradation and accumulates in non-small cell lung cancer (NSCLC) remains unclear, and ubiquitin pathway genes (UPGs) that are critical to NSCLC needs to be systematically identified.

Methods: A total of 696 UPGs (including E1, E2, E3, and deubiquitinases) were silenced by small interfering RNA (siRNA) library in NSCLC cells, the candidates were verified, and their significance was evaluated in patients with NSCLC. The effects of a candidate gene on EGFR were investigated in vitro and in vivo.

Findings: We report 31 candidates that are required for cell proliferation, with the E2 ubiquitin conjugase CDC34 as the most significant one. CDC34 is elevated in tumor tissues in 76 of 114 (66.7%) NSCLCs and inversely associated with prognosis, is higher in smoker patients than nonsmoker patients, and is induced by tobacco carcinogens in normal human lung epithelial cells. Forced expression of CDC34 promotes, whereas knockdown of CDC34 inhibits, NSCLC cell proliferation in vitro and in vivo. CDC34 competes with c-Cbl to bind Y1045 to inhibit polyubiquitination and degradation of EGFR. In EGFR-L858R and EGFR-T790M/Del (exon 19)-driven lung tumor growth in mouse models, knockdown of CDC34 significantly inhibits tumor formation.

Interpretation: These results demonstrate that an E2 enzyme is capable of competing with E3 ligase to stabilize substrates, and CDC34 represents an attractive therapeutic target for NSCLCs.

Funding: National Key Research and Development Program of China, National Natural Science Foundation of China, and the CAMS Innovation Fund for Medical Sciences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2020.102689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047192PMC
March 2020

Emotion-behavior decoupling in individuals with schizophrenia, bipolar disorder, and major depressive disorder.

J Abnorm Psychol 2020 May 13;129(4):331-342. Epub 2020 Jan 13.

Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences.

Failure in translating emotional salience into effortful behavior is thought to be a core feature of anhedonia and avolition in individuals with schizophrenia (SCZ), but little is known about emotion-behavior coupling in individuals with bipolar disorder (BD) and major depressive disorder (MDD). In this study, we compared emotion-behavior correspondence in participants with SCZ, BD, and MDD. Forty-two participants with SCZ, 44 participants with MDD, 43 participants with BD, and 43 healthy controls were recruited. A computerized anticipatory and consummatory pleasure task was used to evaluate emotion-behavior correspondence. Clinical ratings of negative symptoms and self-report anhedonia questionnaires were also administered. We found that participants with SCZ, MDD, and BD exhibited different levels of negative symptoms and self-reported anhedonia, as well as emotion-behavior decoupling. In SCZ participants, both desirable and undesirable images elicited lower correspondence between self-reported liking and behavior. In MDD and BD participants, undesirable images elicited lower emotion-behavior correspondence under both direct stimulus presentation and representation conditions, whereas deficits in emotion-behavior coupling under desirable conditions were only observed when stimuli were present. Taken together, emotion-behavior decoupling showed both common and unique patterns in participants with SCZ, MDD, and BD, and showed some associations with negative symptoms and anhedonia across the combined clinical sample. This finding may be helpful for early identification and the development of novel interventions for different psychiatric diagnoses. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1037/abn0000499DOI Listing
May 2020

Systematic analysis of concentrations of 52 elements in tumor and counterpart normal tissues of patients with non-small cell lung cancer.

Cancer Med 2019 12 23;8(18):7720-7727. Epub 2019 Oct 23.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Many studies have documented the abnormal concentrations of major/trace elements in serum or malignant tissues of patients, but very few works systematically tested the concentrations of elements in tumor tissues in comparison with paired adjacent normal tissues from the same patients.

Methods: Tumor and adjacent normal lung tissues were obtained from 93 patients with previously untreated NSCLC, and 43 patients whose tumor and paired normal lung tissues reached 200 mg or more were selected for measurement of the elements' concentrations using an inductively coupled plasma-atomic emission spectrometer.

Results: We found that the concentrations of the 52 elements varied from 0.4 ng/g tissue (Lu, Pd, and Tm) to 1 658 000 ng/g (Na), 1 951 000 ng/g (P), and 2 495 000 ng/g (K). Thirty eight of the 52 (73.1%) elements showed approximately equal concentrations in tumor and adjacent normal lung tissues of the patients. The concentrations of nine elements (K, P, Mg, Zn, Rb, Cu, Se, Cs, and Tl) in tumor samples were significantly higher than their paired normal lung tissues, and five elements (Na, Fe, Cr, Cd, and Ge) exhibited decreased concentrations in cancer samples compared to counterpart normal lung tissues. Low Fe in tumor samples was associated with smoking history, whereas low Cr was associated with histology (squamous cell carcinoma) of the patients.

Conclusions: Our results demonstrate that measurement of elements' concentrations in both cancer and paired normal tissues is important to get insights into the roles of these elements in carcinogenesis, and therapeutic approaches to normalize the elements are warranted to treat NSCLCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.2629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912044PMC
December 2019

The Aryl hydrocarbon receptor mediates tobacco-induced PD-L1 expression and is associated with response to immunotherapy.

Nat Commun 2019 03 8;10(1):1125. Epub 2019 Mar 8.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Whether tobacco carcinogens enable exposed cells immune escape resulting in carcinogenesis, and why patients who smoke respond better to immunotherapies than non-smokers, remains poorly understood. Here we report that cigarette smoke and the carcinogen benzo(a)pyrene (BaP) induce PD-L1 expression on lung epithelial cells in vitro and in vivo, which is mediated by aryl hydrocarbon receptor (AhR). Anti-PD-L1 antibody or deficiency in AhR significantly suppresses BaP-induced lung cancer. In 37 patients treated with anti-PD-1 antibody pembrolizumab, 13/16 (81.3%) patients who achieve partial response or stable disease express high levels of AhR, whereas 12/16 (75%) patients with progression disease exhibit low levels of AhR in tumor tissues. AhR inhibitors exert significant antitumor activity and synergize with anti-PD-L1 antibody in lung cancer mouse models. These results demonstrate that tobacco smoke enables lung epithelial cells to escape from adaptive immunity to promote tumorigenesis, and AhR predicts the response to immunotherapy and represents an attractive therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-08887-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408580PMC
March 2019

The red wine component ellagic acid induces autophagy and exhibits anti-lung cancer activity in vitro and in vivo.

J Cell Mol Med 2019 01 24;23(1):143-154. Epub 2018 Oct 24.

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Red wine consists of a large amount of compounds such as resveratrol, which exhibits chemopreventive and therapeutic effects against several types of cancers by targeting cancer driver molecules. In this study, we tested the anti-lung cancer activity of 11 red wine components and reported that a natural polyphenol compound ellagic acid (EA) inhibited lung cancer cell proliferation at an efficacy approximately equal to that of resveratrol. EA markedly increased the expression of the autophagosomal marker LC3-II as well as inactivation of the mechanistic target of rapamycin signalling pathway. EA elevated autophagy-associated cell death by down-regulating the expression of cancerous inhibitor of protein phosphatase 2A (CIP2A), and CIP2A overexpression attenuated EA-induced autophagy of lung cancer cells. Treating tumour-bearing mice with EA resulted in significant inhibition of tumour growth with suppression of CIP2A levels and increased autophagy. In addition, EA potentiated the inhibitory effects of the natural compound celastrol on lung cancer cells in vitro and in vivo by enhancing autophagy and down-regulating CIP2A. These findings indicate that EA may be a promising chemotherapeutic agent for lung cancer, and that the combination of EA and celastrol may have applicability for the treatment of this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.13899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307804PMC
January 2019

[Establishment of fingerprint of Astragali Radix polysaccharides based on endo-1,4-β-mannanase hydrolysis and identification of Astragali Radix of different germplasm resources].

Zhongguo Zhong Yao Za Zhi 2018 Jul;43(14):2964-2972

University of Louisville, Louisville 40292, America.

The polysaccharides of different germplasm resources of Astragalus membranaceus var. mongholicus〓(cultured Astragalus Radix (RA) and natural RA) and A. membranaceus (MJ) (cultured RA and natural RA) were studied by using the optimal enzymatic conditions of endo-1,4-β-mannanase. Saccharide fingerprints were obtained for the identification and evaluation of the germplasm resources of RA by Fluorophore-assisted Carbohydrate Electrophoresis (FACE). The data were analyzed by principal component analysis to obtain the difference between RA of different germplasm resources. The results showed that trisaccharide, tetrasaccharide and pentasaccharide of endo-1,4-β-mannanase hydrolyzate could be used as the differential fragments to distinguish MG (cultured RA and natural RA); the pentasaccharide and hexasaccharide can be used as differentially expressed carbohydrate fragments that distinguish MJ (cultured RA and natural RA); the trisaccharide and tetrasaccharide can be used as the differential fragments to distinguish the cultured MG and cultured MJ. Studies have shown that polysaccharide products degraded by endo-1,4-β-mannanase can well distinguish RA species (MG and MJ), growth mode (cultured RA and natural RA). This study laid the foundation for the quality evaluation of Astragalus medicinal herbs and screening of active oligosaccharides.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19540/j.cnki.cjcmm.20180315.003DOI Listing
July 2018

Genome-wide identification of transcription factors that are critical to non-small cell lung cancer.

Cancer Lett 2018 10 18;434:132-143. Epub 2018 Jul 18.

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & School of Medicine, University of Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

To systematically unveil transcription factors (TFs) that are critical to lung carcinogenesis, here we conducted a genome-wide lethality screening in non-small cell lung cancer (NSCLC) cells and reported that among the 1530 TFs tested, 21 genes were required for NSCLC cell proliferation and were negatively or positively associated with overall survival (OS) of patients with NSCLC. These included 11 potential tumor suppressing genes (AFF3, AhR, AR, CBFA2T3, CHD4, KANK2, NR3C2, PTEN, PRDM16, RB1, and STK11) and 10 potential oncogenic TFs (BARX1, DLX6, ELF3, EN1, ETV1, FOXE1, HOXB7, IRX4, IRX5, and SALL1). The expression levels of IRX5 were positively associated with OS of smoker and inversely associated with OS of non-smoker patients with lung adenocarcinoma. We showed that tobacco carcinogen benzo(a)pyrene (BaP) induced upregulation of IRX5 in lung epithelial cells, and Cyclin D1 was a downstream target of IRX5. Furthermore, silencing of IRX5 by lentivirus mediated transfection of short hairpin RNA significantly inhibited tumor growth in nude mice. These results indicate that tobacco smoke can modulate TFs to facilitate lung carcinogenesis, and inhibition of IRX5 may have therapeutic potentials in NSCLCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2018.07.020DOI Listing
October 2018

[Quantitative apportionment of slope aspect and altitude to soil moisture and temperature and plant distribution on alpine meadow].

Ying Yong Sheng Tai Xue Bao 2017 May;28(5):1489-1497

College of Grassland Science, Gansu Agricultural University/Ministry of Education Key Laboratory of Grassland Ecosystem/Sino-USA Center for Grazing Land Ecosystem Sustainability, Lanzhou 730070, China.

For understanding the effect of aspect and altitude of hill on soil moisture and temperature as well as the vegetation community, we selected an alpine meadow located on a hill in north-eastern Tibet Plateau as our study area. Data on soil moisture and temperature, as well as plant distribution pattern in this mountain ecosystem were collected. We used regression analysis, CCA ordination and variance decomposition, to determine the impacts of the key factors (aspect, altitude, soil temperature and moisture) on plant diversity distribution in 189 sample sites of the hill. The results showed that the plant diversity of shady aspect and bottomland was highest and lowest, respectively. The plant diversity of the shady aspect and on the ridge of the hill increased initially and then decreased with the increasing altitude, but the plant diversity of the sunny aspect increased with the increasing altitude. At 0-30 cm soil layer, the soil temperature of the sunny aspect was higher than that of other aspects, but the soil temperature at 0-20 cm soil layer did not change with the increa-sing altitude. The soil moisture of shady aspect was higher than that of other aspects, and increased with the increasing altitude. The aspect and altitude explained 100% of soil temperature changes and 51.8% of soil moisture variation. Aspect alone explained 72.2% of soil temperature variation and altitude alone explained 51.8% of soil moisture variation, which had the highest contribution rate individually. Most plants were distributed on the shady aspect and on the ridge, and at medium altitude. Sedges mainly grew on the shady aspect, while Gramineae grew on the sunny aspect, the ridge was an ecotone. Cyperaceae, Gramineae and Leguminosae were mainly distributed in low altitude zone. Hill aspect and altitude totally explained 28.6% of plant abundance variation, hill aspect alone explained 19.9% of plant abundance variation. The management of grassland production and ecological restoration in alpine meadow ecosystem should consider the effect of landform on soil and vegetation, and the hill aspect should be priority factor instead of altitude when planning management interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13287/j.1001-9332.201705.032DOI Listing
May 2017

[Evaluation and selection of species diversity index under grazing disturbance in alpine mea-dow].

Ying Yong Sheng Tai Xue Bao 2017 Jun;28(6):1824-1832

College of Grassland Science, Gansu Agricultural University/Ministry of Education Key Laboratory of Grassland Ecosystem/Sino-USA Center for Grazing Land Ecosystem Sustainability, Lanzhou 730070, China.

The research selected the plots of six grazing intensities in an alpine meadow in north-eastern Tibet Plateau in four years (2012-2015) and studied the relation between ten species diversity indexes, including two measured indexes (Richness and Abundance) in field and two indexes of each dominance, evenness, richness, integrated indexes, and grazing intensity as well as grazing time aiming at scientific selection of biodiversity index under grazing disturbance. The results indicated that the abundance was a better index than importance value to calculate biodiversity level because it was more sensitive to grazing disturbance. Dominance indexes, including Berger-Parker and Dominance, were not sensitive to grazing intensity and grazing time because they could not clarify the effect of grazing disturbance on dominant species in plant community. Evenness indexes, including Equitability and Evenness, had not relation with grazing intensity, however, the evenness index had a negative correlation with grazing time and it was not influenced by occasional species as well as the variation coefficient of species abundance. Hereby, the evenness index could be chosen for studying evenness change at temporal scale. Richness indexes, including Menhinick and Margalef, had no relation with grazing time, however, the Margalef index had a positive correlation with grazing intensity and the index was not influenced by occasional species. Integrated index, including Shannon and Simpson indexes, had no relation with grazing intensity, however, the Shannon index had a significant positive correlation with species richness and abundance and the index was not influenced by occasional species, and it significantly increased along grazing time. Hereby, Shannon index could be used as an index of studying plant species diversity in long-term. In ten diversity indexes, only the measured indexes in field, including richness and abundance, were signifi-cantly negatively correlated with grazing intensity, and positively correlated with grazing time, and the two indexes were not influenced by occasional species. Hereby, the combination of species richness and abundance mea-sured in field could be considered as the most important indexes for studying plant species diversity under grazing disturbance. Besides, the selection of biodiversity indexes must consider the spatial-temporal feature of grazing, diversity components and research purpose.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13287/j.1001-9332.201706.026DOI Listing
June 2017

[Relation between species distribution of plant community and soil factors under grazing in alpine meadow].

Ying Yong Sheng Tai Xue Bao 2017 Dec;28(12):3891-3898

College of Grassland Science, Gansu Agricultural University/Ministry of Education Key Laboratory of Grassland Ecosystem/Sino-USA Centers for Grazing Land Ecosystem Sustainability, Lanzhou 730070, China.

The research selected the alpine meadow located in the northeastern margin of the Qinghai-Tibet Plateau to study the changes of vegetation community and soil properties under different grazing intensities, as well as the quantitative relation between the distribution patterns of plant species and the physical and chemical properties of soil. The results showed that the grazing caused the differentiation of the initial vegetation community with the dominant plants, Elymus nutans and Stipa grandis. In the plots with high and low grazing intensities, the dominant plants had changed to Kobresia humilis and Melissitus ruthenica, and E. nutans and Poa crymophila, respectively. With the increase of grazing intensity, the plant richness, importance value and biomass were significantly decreased. The sequence of plant species importance value in each plot against grazing intensity could be fitted by a logarithmic model. The number of required plant species was reduced while the importance value of the remaining plant species accounted for 50% of the importance value in the whole vegetation community. The available P, available K, soil compaction, soil water content, stable infiltration rate and large aggregate index were significantly changed with grazing intensity, however, the changes were different. The CCA ordination showed that the soil compaction was the key factor affecting the distribution pattern of the plant species under grazing. The variance decomposition indicated that the soil factors together explained 30.5% of the distribution of the plant species, in particular the soil physical properties alone explained 22.8% of the distribution of the plant species, which had the highest rate of contribution to the plant species distribution. The soil physical properties affected the distribution pattern of plant species on grazed alpine meadow.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13287/j.1001-9332.201712.005DOI Listing
December 2017

Genomic variations in paired normal controls for lung adenocarcinomas.

Oncotarget 2017 Nov 24;8(61):104113-104122. Epub 2017 Oct 24.

Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

Somatic genomic mutations in lung adenocarcinomas (LUADs) have been extensively dissected, but whether the counterpart normal lung tissues that are exposed to ambient air or tobacco smoke as the tumor tissues do, harbor genomic variations, remains unclear. Here, the genome of normal lung tissues and paired tumors of 11 patients with LUAD were sequenced, the genome sequences of counterpart normal controls (CNCs) and tumor tissues of 513 patients were downloaded from TCGA database and analyzed. In the initial screening, genomic alterations were identified in the "normal" lung tissues and verified by Sanger capillary sequencing. In CNCs of TCGA datasets, a mean of 0.2721 exonic variations/Mb and 5.2885 altered genes per sample were uncovered. The C:G→T:A transitions, a signature of tobacco carcinogen N-methyl-N-nitro-N-nitrosoguanidine, were the predominant nucleotide changes in CNCs. 16 genes had a variant rate of more than 2%, and CNC variations in , , , , , and were associated with poor prognosis whereas alterations in and were associated with favorable clinical outcome of the patients. This study identified the genomic alterations in CNC samples of LUADs, and further highlighted the DNA damage effect of tobacco on lung epithelial cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.22020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732791PMC
November 2017

Somatic Mutations and Splicing Variants of Focal Adhesion Kinase in Non-Small Cell Lung Cancer.

J Natl Cancer Inst 2018 02;110(2)

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences and University of Chinese Academy of Sciences, Beijing, China.

Background: Overexpression of focal adhesion kinase (FAK) has been reported in lung cancer, but the somatic mutations and alternative splicing variants of this nonreceptor tyrosine kinase remain to be investigated.

Methods: FAK in 91 lung cancer patients was sequenced using genomic DNA and cDNA samples of tumor and paired normal lung tissues as templates, and the RNA-seq data of The Cancer Genome Atlas (TCGA) data set were assessed. The biological functions of abnormal FAK transcripts and their response to FAK inhibitors were analyzed in eight cell lines using tyrosine kinase activity assay, trypan blue exclusion assay, MTT (3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide) assay, and transwell assay.

Results: We identified an internal tandem duplication (ITD), an A1004S point mutation, an exon 5-27 deletion (ΔE5-27) truncation variant, and four FAK6,7 splicing variants (containing exons for Boxes 6 and 7) in seven (7.7%) patients. Smokers had more FAK abnormalities than nonsmokers. In FAK-ITD, the sequence encoding the C-terminal of the FERM domain and kinase domain was duplicated in-frame and produced a protein product with elevated autophosphorylation and sensitivity to FAK inhibitors. FAK6,7 was detected in the tumor but not counterpart normal lung tissues of four (4.4%) patients. In TCGA RNA-seq data, Box 6 and/or Box 7 (Box 6/7)-containing FAK variants were positive in 42 (8.3%) of 508 lung adenocarcinomas (LUADs) and 37 (7.4%) of 501 lung squamous cell carcinomas, and smokers had higher expression of Box 6/7 (+) FAK than reformed or nonsmokers with LUAD. FAK6,7 promoted cell proliferation and migration, exhibited increased autophosphorylation, and was more sensitive to FAK inhibitor compared with wild-type FAK.

Conclusions: Somatic mutations and splicing variants of FAK may have a role in lung carcinogenesis and represent potential biomarkers for FAK-targeted therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djx157DOI Listing
February 2018

Complex Roles of Annexin A2 in Host Blood-Brain Barrier Invasion by Cryptococcus neoformans.

CNS Neurosci Ther 2017 Apr 28;23(4):291-300. Epub 2017 Jan 28.

Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Institute of Medical Mycology, Second Military Medical University, Shanghai, China.

Introduction: Fungal transversal across the brain microvascular endothelial cells (BMECs) is the essential step for the development of cryptococcal meningoencephalitis. Annexin A2 (AnxA2) is an important signaling protein involved in several intracellular processes such as membrane trafficking, endocytosis, and exocytosis.

Aim: To investigate the roles and mechanism of AnxA2 during cryptococcal transversal of BMECs.

Results: Cryptococcus neoformans infection initiated upregulation of AnxA2 in mouse BMECs. Blockade with anti-AnxA2 antibody led to a reduction in fungal transcytosis activity but no change in its adhesion efficiency. Intriguingly, AnxA2 depletion caused a significant increase in fungal association activity but had no effect on their transcytosis. AnxA2 suppression resulted in marked reduction in its partner protein S100A10, and S100A10 suppression in BMECs significantly reduced the cryptococcal transcytosis efficiency. Furthermore, AnxA2 dephosphorylation at Tyr23 and dephosphorylation of downstream cofilin were required for cryptococcal transversal of BMECs, both of which might be primarily involved in the association of C. neoformans with host cells.

Conclusions: Our work indicated that AnxA2 played complex roles in traversal of C. neoformans across host BMECs, which might be dependent on downstream cofilin to inhibit fungal adhesion but rely on its partner S100A10 to promote cryptococcal transcytosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cns.12673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492751PMC
April 2017

Six-band terahertz metamaterial absorber based on the combination of multiple-order responses of metallic patches in a dual-layer stacked resonance structure.

Sci Rep 2017 01 25;7:41373. Epub 2017 Jan 25.

School of Physics and Electronics, Hunan University, Changsha 410082, China.

This paper reports on a numerical study of the six-band metamaterial absorber composed of two alternating stack of metallic-dielectric layers on top of a continuous metallic plane. Six obvious resonance peaks with high absorption performance (average larger than 99.37%) are realized. The first, third, fifth, and the second, fourth, sixth resonance absorption bands are attributed to the multiple-order responses (i.e., the 1-, 3- and 5-order responses) of the bottom- and top-layer of the structure, respectively, and thus the absorption mechanism of six-band absorber is due to the combination of two sets of the multiple-order resonances of these two layers. Besides, the size changes of the metallic layers have the ability to tune the frequencies of the six-band absorber. Employing the results, we also present a six-band polarization tunable absorber through varying the sizes of the structure in two orthogonal polarization directions. Moreover, nine-band terahertz absorber can be achieved by using a three-layer stacked structure. Simulation results indicate that the absorber possesses nine distinct resonance bands, and average absorptivities of them are larger than 94.03%. The six-band or nine-band absorbers obtained here have potential applications in many optoelectronic and engineering technology areas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep41373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264608PMC
January 2017

Proteomic identification of the oncoprotein STAT3 as a target of a novel Skp1 inhibitor.

Oncotarget 2017 Jan;8(2):2681-2693

Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

The S phase kinase-associated protein 1 (Skp1), an adaptor protein of the Skp1-Cul1-F-box protein complex, binds the ubiquitin E3 ligase Skp2 and is critical to its biological functions. Targeting of Skp1 by a small compound 6-O-angeloylplenolin (6-OAP) results in dissociation and degradation of Skp2 and mitotic arrest of lung cancer cells. Here, by using a proteome microarray containing 16,368 proteins and a biotinylated 6-OAP, we identified 99 proteins that could bind 6-OAP, with Skp1 and STAT3 sitting at the central position of the 6-OAP interactome. 6-OAP formed hydrogen bonds with Ser611/Ser613/Arg609 at the SH2 domain of STAT3 and inhibited the constitutive and interleukin-6-induced phosphorylated STAT3 (pSTAT3), leading to inhibitory effects on lung cancer cells and suppression of Skp2 transcription. STAT3 was overexpressed in tumor samples compared to counterpart normal lung tissues and was inversely associated with prognosis of the patients. 6-OAP inhibited tumor growth in SCID mice intravenously injected with lung cancer cells, and downregulated both STAT3 and Skp2 in tumor samples. Given that 6-OAP is a Skp1 inhibitor, our data suggest that this compound may target Skp1 and STAT3 to suppress Skp2, augmenting its anti-lung cancer activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.13153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356833PMC
January 2017

Long non-coding RNA stabilizes the Y-box-binding protein 1 and regulates the epidermal growth factor receptor to promote lung carcinogenesis.

Oncotarget 2016 Sep;7(37):59556-59571

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

Indoor and outdoor air pollution has been classified as group I carcinogen in humans, but the underlying tumorigenesis remains unclear. Here, we screened for abnormal long noncoding RNAs (lncRNAs) in lung cancers from patients living in Xuanwei city which has the highest lung cancer incidence in China due to smoky coal combustion-generated air pollution. We reported that Xuanwei patients had much more dysregulated lncRNAs than patients from control regions where smoky coal was not used. The lncRNA CAR intergenic 10 (CAR10) was up-regulated in 39/62 (62.9%) of the Xuanwei patients, which was much higher than in patients from control regions (32/86, 37.2%; p=0.002). A multivariate regression analysis showed an association between CAR10 overexpression and air pollution, and a smoky coal combustion-generated carcinogen dibenz[a,h]anthracene up-regulated CAR10 by increasing transcription factor FoxF2 expression. CAR10 bound and stabilized transcription factor Y-box-binding protein 1 (YB-1), leading to up-regulation of the epidermal growth factor receptor (EGFR) and proliferation of lung cancer cells. Knockdown of CAR10 inhibited cell growth in vitro and tumor growth in vivo. These results demonstrate the role of lncRNAs in environmental lung carcinogenesis, and CAR10-YB-1 represents a potential therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.10006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312331PMC
September 2016

Xinfeng capsule for the treatment of rheumatoid arthritis patients with decreased pulmonary function--a randomized controlled clinical trial.

Chin J Integr Med 2016 Mar 27;22(3):168-76. Epub 2016 Jan 27.

Department of Rheumatology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031, China.

Objective: To determine the effectiveness and safety of Xinfeng Capsules (XFC) for the treatment of rheumatoid arthritis (RA) patients with decreased pulmonary function.

Methods: This was a randomized controlled clinical trial of 80 RA patients. Participants were assigned to the trial group (40 cases) and the control group (40 cases) by block randomization. The trial group was treated with XFC, three pills each time three times daily for 2 months. The control group was treated with tripterygium glycoside (TPT), two pills each time three times daily for 2 months. Both groups were followed up after 2 months. The clinical effects, changes in joint and pulmonary function, and quality of life before and after treatment were observed; safety indices were also evaluated.

Results: Pain, swelling, tenderness, and duration of morning stiffness of joints were obviously decreased after treatment in both the trial and the control groups compared with baseline (P<0.01). Compared with before treatment, hand grip strength increased significantly after treatment in the trial group (P=0.0000); pulmonary function parameters such as forced expiratory volume in the first second of expiration/forced vital capacity (FEV1/FVC), 50% of the expiratory flow of forced vital capacity (FEF50), carbon monoxide diffusing capacity (DLco) were increased (P<0.01 or P<0.05); measures of quality of life such as role-physical, body pain, vitality and mental health were also improved after treatment in the trial group (all P<0.05). Joint swelling in the trial group decreased compared with the control group (P=0.0043), while hand grip strength was increased after treatment (P=0.0000). The increase in FEF50, DLco, and the dimensions of quality of life such as vitality and mental health were all significantly greater in the trial group than the control group (P<0.05 or P<0.01).

Conclusions: XFC not only relieved joint pain in RA patients, but also significantly improved the ventilation and diffusion function of the lungs. Therefore, XFC could improve the whole body function and enhance the quality of life of RA patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11655-015-2093-6DOI Listing
March 2016

The chemokine CXCL13 in lung cancers associated with environmental polycyclic aromatic hydrocarbons pollution.

Elife 2015 Nov 13;4. Epub 2015 Nov 13.

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

More than 90% of lung cancers are caused by cigarette smoke and air pollution, with polycyclic aromatic hydrocarbons (PAHs) as key carcinogens. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China, attributed to smoky coal combustion-generated PAH pollution. Here, we screened for abnormal inflammatory factors in non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used, and found that a chemokine CXCL13 was overexpressed in 63/70 (90%) of Xuanwei NSCLCs and 44/71 (62%) of smoker and 27/60 (45%) of non-smoker CR patients. CXCL13 overexpression was associated with the region Xuanwei and cigarette smoke. The key carcinogen benzo(a)pyrene (BaP) induced CXCL13 production in lung epithelial cells and in mice prior to development of detectable lung cancer. Deficiency in Cxcl13 or its receptor, Cxcr5, significantly attenuated BaP-induced lung cancer in mice, demonstrating CXCL13's critical role in PAH-induced lung carcinogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.09419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764582PMC
November 2015

Skp1 in lung cancer: clinical significance and therapeutic efficacy of its small molecule inhibitors.

Oncotarget 2015 Oct;6(33):34953-67

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China.

Skp1 is an essential adaptor protein of the Skp1-Cul1-F-box protein complex and is able to stabilize the conformation of some ubiquitin E3 ligases. However, the role Skp1 plays during tumorigenesis remains unclear and Skp1-targeting agent is lacking. Here we showed that Skp1 was overexpressed in 36/64 (56.3%) of non-small cell lung cancers, and elevated Skp1 was associated with poor prognosis. By structure-based high-throughput virtual screening, we found some Skp1-targeting molecules including a natural compound 6-O-angeloylplenolin (6-OAP). 6-OAP bound Skp1 at sites critical to Skp1-Skp2 interaction, leading to dissociation and proteolysis of oncogenic E3 ligases NIPA, Skp2, and β-TRCP, and accumulation of their substrates Cyclin B1, P27 and E-Cadherin. 6-OAP induced prometaphase arrest and exerted potent anti-lung cancer activity in two murine models and showed low adverse effect. These results indicate that Skp1 is critical to lung cancer pathogenesis, and Skp1 inhibitor inactivates crucial oncogenic E3 ligases and exhibits significant therapeutic potentials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.5547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741501PMC
October 2015

Down-regulation of microRNA-144 in air pollution-related lung cancer.

Sci Rep 2015 Sep 23;5:14331. Epub 2015 Sep 23.

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences &Graduate School of the University of Chinese Academy of Sciences, Beijing 100101.

Air pollution has been classified as a group 1 carcinogen in humans, but the underlying tumourigenic mechanisms remain unclear. In Xuanwei city of Yunnan Province, the lung cancer incidence is among the highest in China, owing to severe air pollution generated by the combustion of smoky coal, providing a unique opportunity to dissect lung carcinogenesis. To identify abnormal miRNAs critical for air pollution-related tumourigenesis, we performed microRNA microarray analysis in 6 Xuanwei non-small cell lung cancers (NSCLCs) and 4 NSCLCs from control regions where smoky coal was not used. We found 13 down-regulated and 2 up-regulated miRNAs in Xuanwei NSCLCs. Among them, miR-144 was one of the most significantly down-regulated miRNAs. The expanded experiments showed that miR-144 was down-regulated in 45/51 (88.2%) Xuanwei NSCLCs and 34/54 (63%) control region NSCLCs (p = 0.016). MiR-144 interacted with the oncogene Zeb1 at 2 sites in its 3' untranslated region, and a decrease in miR-144 resulted in increased Zeb1 expression and an epithelial mesenchymal transition phenotype. Ectopic expression of miR-144 suppressed NSCLCs in vitro and in vivo by targeting Zeb1. These results indicate that down-regulation of miR-144 is critical for air pollution-related lung cancer, and the miR-144-Zeb1 signalling pathway could represent a potential therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep14331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585805PMC
September 2015

Characterization of Somatic Mutations in Air Pollution-Related Lung Cancer.

EBioMedicine 2015 Jun 7;2(6):583-90. Epub 2015 Apr 7.

State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, and Shanghai Center for Systems Biomedicine, SJTU, Shanghai 200025, China.

Air pollution has been classified as Group 1 carcinogenic to humans, but the underlying tumorigenesis remains unclear. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China attributed to severe air pollution generated by combustion of smoky coal, providing a unique opportunity to dissect lung carcinogenesis of air pollution. Here we analyzed the somatic mutations of 164 non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used. Whole genome sequencing revealed a mean of 289 somatic exonic mutations per tumor and the frequent C:G → A:T nucleotide substitutions in Xuanwei NSCLCs. Exome sequencing of 2010 genes showed that Xuanwei and CR NSCLCs had a mean of 68 and 22 mutated genes per tumor, respectively (p < 0.0001). We found 167 genes (including TP53, RYR2, KRAS, CACNA1E) which had significantly higher mutation frequencies in Xuanwei than CR patients, and mutations in most genes in Xuanwei NSCLCs differed from those in CR cases. The mutation rates of 70 genes (e.g., RYR2, MYH3, GPR144, CACNA1E) were associated with patients' lifetime benzo(a)pyrene exposure. This study uncovers the mutation spectrum of air pollution-related lung cancers, and provides evidence for pollution exposure-genomic mutation relationship at a large scale.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2015.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534757PMC
June 2015

Celastrol induces proteasomal degradation of FANCD2 to sensitize lung cancer cells to DNA crosslinking agents.

Cancer Sci 2015 Jul 26;106(7):902-8. Epub 2015 May 26.

Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

The Fanconi anemia (FA) pathway plays a key role in interstrand crosslink (ICL) repair and maintenance of the genomic stability, while inhibition of this pathway may sensitize cancer cells to DNA ICL agents and ionizing radiation (IR). The active FA core complex acts as an E3 ligase to monoubiquitinate FANCD2, which is a functional readout of an activated FA pathway. In the present study, we aimed to identify FANCD2-targeting agents, and found that the natural compound celastrol induced degradation of FANCD2 through the ubiquitin-proteasome pathway. We demonstrated that celastrol downregulated the basal and DNA damaging agent-induced monoubiquitination of FANCD2, followed by proteolytic degradation of the substrate. Furthermore, celastrol treatment abrogated the G2 checkpoint induced by IR, and enhanced the ICL agent-induced DNA damage and inhibitory effects on lung cancer cells through depletion of FANCD2. These results indicate that celastrol is a FANCD2 inhibitor that could interfere with the monoubiquitination and protein stability of FANCD2, providing a novel opportunity to develop FA pathway inhibitor and combinational therapy for malignant neoplasms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.12679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520643PMC
July 2015

Independent controls of differently-polarized reflected waves by anisotropic metasurfaces.

Sci Rep 2015 Apr 15;5:9605. Epub 2015 Apr 15.

State Key Laboratory of Millimeter Waves, School of Information Science and Engineering, Southeast University, Nanjing 210096, China.

We propose a kind of anisotropic planar metasurface, which has capacity to manipulate the orthogonally-polarized electromagnetic waves independently in the reflection mode. The metasurface is composed of orthogonally I-shaped structures and a metal-grounded plane spaced by a dielectric isolator, with the thickness of about 1/15 wavelength. The normally incident linear-polarized waves will be totally reflected by the metal plane, but the reflected phases of x- and y-polarized waves can be controlled independently by the orthogonally I-shaped structures. Based on this principle, we design four functional devices using the anisotropic metasurfaces to realize polarization beam splitting, beam deflection, and linear-to-circular polarization conversion with a deflection angle, respectively. Good performances have been observed from both simulation and measurement results, which show good capacity of the anisotropic metasurfaces to manipulate the x- and y-polarized reflected waves independently.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep09605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397642PMC
April 2015

Tobacco smoke induces production of chemokine CCL20 to promote lung cancer.

Cancer Lett 2015 Jul 9;363(1):60-70. Epub 2015 Apr 9.

State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences & Graduate School of the University of Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

Tobacco kills nearly 6 million people each year, and 90% of the annual 1.59 million lung cancer deaths worldwide are caused by cigarette smoke. Clinically, a long latency is required for individuals to develop lung cancer since they were first exposed to smoking. In this study, we aimed to identify clinical relevant inflammatory factors that are critical for carcinogenesis by treating normal human lung epithelial cells with tobacco carcinogen nicotine-derived nitrosaminoketone (NNK) for a long period (60 days) and systematic screening in 84 cytokines/chemokines. We found that a chemokine CCL20 was significantly up-regulated by NNK, and in 78/173 (45.1%) patients the expression of CCL20 was higher in tumor samples than their adjacent normal lung tissues. Interestingly, CCL20 was up-regulated in 48/92 (52.2%) smoker and 29/78 (37.2%) nonsmoker patients (p = 0.05), and high CCL20 was associated with poor prognosis. NNK induced the production of CCL20, which promoted lung cancer cell proliferation and migration. In addition, an anti-inflammation drug, dexamethasone, inhibited NNK-induced CCL20 production and suppressed lung cancer in vitro and in vivo. These results indicate that CCL20 is crucial for tobacco smoke-caused lung cancer, and anti-CCL20 could be a rational approach to fight against this deadly disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2015.04.005DOI Listing
July 2015

Independent control of differently-polarized waves using anisotropic gradient-index metamaterials.

Sci Rep 2014 Sep 18;4:6337. Epub 2014 Sep 18.

State Key Laboratory of Millimeter Waves, School of Information Science and Engineering, Southeast University, Nanjing 210096, China.

We propose a kind of anisotropic gradient-index (GRIN) metamaterials, which can be used to control differently-polarized waves independently. We show that two three- dimensional (3D) planar lenses made of such anisotropic GRIN metamaterials are able to make arbitrary beam deflections for the vertical (or horizontal) polarization but have no response to the horizontal (or vertical) polarization. Then the vertically- and horizontally-polarized waves are separated and controlled independently to deflect to arbitrarily different directions by designing the anisotropic GRIN planar lenses. We make experimental verifications of the lenses using such a special metamaterial, which has both electric and magnetic responses simultaneously to reach approximately equal permittivity and permeability. Hence excellent impedance matching is obtained between the GRIN planar lenses and the air. The measurement results demonstrate good performance on the independent controls of differently-polarized waves, as observed in the numerical simulations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep06337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166714PMC
September 2014

[Treatment of rheumatoid arthritis by xinfeng capsule: an efficacy observation].

Zhongguo Zhong Xi Yi Jie He Za Zhi 2013 Dec;33(12):1599-602

Department of Rheumatology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China.

Objective: To observe the curative effect of Xinfeng Capsule (XC) in treatment of rheumatoid arthritis (RA).

Methods: Recruited were 80 active RA patients, who were randomly assigned to the normal control group and the treatment group, 40 in each group. All patients received the same routine anti-rheumatic treatment: Methotrexate 10 mg per week; Diclofenac 50 mg when pain was obvious, twice daily. Patients in the treatment group took XC 3 tablets each time, thrice daily. All treatment lasted for 12 consecutive weeks. Serum iron (SI), serum ferritin (SF), transferrin (TRF); and RA disease activity index (DAS-28) were detected in all patients.

Results: XC could improve HAQ, DAS-28, hypersensitive C reactive protein (hs-CRP), prostaglandins A (PGA), erythrocyte sedimentation rate (ESR), number of swelling joints, number of tender joints, and morning stiffness time in acute RA patients, showing statistical difference when compared with those of the control group (P < 0.01, P < 0.05). Compared with the control group, SI, SF, DAS-28, and TRF significantly decreased in the treatment group (P < 0.05).

Conclusion: XC could improve DAS-28, and SI reserve in patients with active RA, and lower DAS-28 related indicators.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2013
-->