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Sökning: WFRF:(Zhang Hongxia)

  • Resultat 1-16 av 16
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1.
  • Chen, Liangliang, et al. (författare)
  • User-Friendly Genetic Conditional Knockout Strategies by CRISPR/Cas9
  • 2018
  • Ingår i: STEM CELLS INTERNATIONAL. - : HINDAWI LTD. - 1687-966X .- 1687-9678.
  • Tidskriftsartikel (refereegranskat)abstract
    • Loss-of-function studies are critically important in gene functional analysis of model organisms and cells. However, conditional gene inactivation in diploid cells is difficult to achieve, as it involves laborious vector construction, multifold electroporation, and complicated genotyping. Here, a strategy is presented for generating biallelic conditional gene and DNA regulatory region knockouts in mouse embryonic stem cells by codelivery of CRISPR-Cas9 and short-homology-arm targeting vectors sequentially or simultaneously. Collectively, a simple and rapid method was presented to knock out any DNA element conditionally. This approach will facilitate the functional studies of essential genes and regulatory regions during development.
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2.
  • Hu, Min, et al. (författare)
  • Hyperandrogenism and insulin resistance induce gravid uterine defects in association with mitochondrial dysfunction and aberrant ROS production.
  • 2019
  • Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 316:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Women with polycystic ovary syndrome (PCOS) are at increased risk of miscarriage, which often accompanies the hyperandrogenism and insulin resistance seen in these patients. However, neither the combinatorial interaction between these two PCOS-related etiological factors nor the mechanisms of their actions in the uterus during pregnancy are well understood. We hypothesised that hyperandrogensim and insulin resistance exert a causative role in miscarriage by inducing defects in uterine function that are accompanied by mitochondrial-mediated oxidative stress, inflammation and perturbed gene expression. Here we tested this hypothesis by studying the metabolic, endocrine and uterine abnormalities in pregnant rats after exposure to daily injection of 5α-dihydrotestosterone (DHT, 1.66 mg/kg body weight/day) and/or insulin (6.0 IU/day) from gestational day 7.5 to 13.5. We showed that while DHT-exposed and insulin-exposed pregnant rats presented impaired insulin sensitivity, DHT+insulin-exposed pregnant rats exhibited hyperandrogenism and peripheral insulin resistance, which mirrors pregnant PCOS patients. Compared to controls, hyperandrogenism and insulin resistance in the dam was associated with alterations in uterine morphology and aberrant expression of genes responsible for decidualization, placentation, angiogenesis and insulin signaling. Moreover, we observed changes in uterine mitochondrial function and homeostasis and suppression of both oxidative and antioxidative defenses in response to the hyperandrogenism and insulin resistance. These findings demonstrate that hyperandrogenism and insulin resistance induce mitochondria-mediated damage and a resulting imbalance between oxidative and antioxidative stress responses in the gravid uterus.
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3.
  • Hu, Min, et al. (författare)
  • Perturbed ovarian and uterine glucocorticoid receptor signaling accompanies the balanced regulation of mitochondrial function and NFκB-mediated inflammation under conditions of hyperandrogenism and insulin resistance.
  • 2019
  • Ingår i: Life sciences. - : Elsevier BV. - 1879-0631 .- 0024-3205. ; 232
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed to determine whether glucocorticoid receptor (GR) signaling, mitochondrial function, and local inflammation in the ovary and uterus are intrinsically different in rats with hyperandrogenism and insulin resistance compared to controls.Female Sprague Dawley rats were exposed to daily injections of human chorionic gonadotropin and/or insulin.In both the ovary and the uterus, decreased expression of the two GR isoforms was concurrent with increased expression of Fkbp51 but not Fkbp52 mRNA in hCG+insulin-treated rats. However, these rats exhibited contrasting regulation of Hsd11b1 and Hsd11b2 mRNAs in the two tissues. Further, the expression of several oxidative phosphorylation-related proteins decreased in the ovary and uterus following hCG and insulin stimulation, in contrast to increased expression of many genes involved in mitochondrial function and homeostasis. Additionally, hCG+insulin-treated rats showed increased expression of ovarian and uterine NFκB signaling proteins and Tnfaip3 mRNA. The mRNA expression of Il1b, Il6, and Mmp2 was decreased in both tissues, while the mRNA expression of Tnfa, Ccl2, Ccl5, and Mmp3 was increased in the uterus. Ovaries and uteri from animals co-treated with hCG and insulin showed increased collagen deposition compared to controls.Our observations suggest that hyperandrogenism and insulin resistance disrupt ovarian and uterine GR activation and trigger compensatory or adaptive effects for mitochondrial homeostasis, allowing tissue-level maintenance of mitochondrial function in order to limit ovarian and uterine dysfunction. Our study also suggests that hyperandrogenism and insulin resistance activate NFκB signaling resulting in aberrant regulation of inflammation-related gene expression.
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4.
  • Zhang, Hongxia, et al. (författare)
  • Effects of angular misalignment in interferometric detection of distributed polarization coupling
  • 2009
  • Ingår i: Measurement science and technology. - : IOP Publishing. - 0957-0233 .- 1361-6501. ; 20:9, s. 095112-
  • Tidskriftsartikel (refereegranskat)abstract
    • White light interferometry is used to measure the distributed polarization coupling (DPC) in polarization-maintaining fibers (PMFs). By using a scanning Michelson interferometer to compensate the optical path difference (OPD) induced by the modal birefringence of PMFs, both the coupling strength and positions of the coupling points can be acquired. In ideal DPC measurement, the two reflective mirrors on the fixed and scanning arms of the Michelson interferometer are normal to each other. But in practice, the movable reflective mirror cannot be aligned normally to the fixed mirror exactly, which leads to an angular misalignment. The angular misalignment causes a variation of the OPD, which will reduce the fringe visibility. The theoretical simulation is investigated correspondingly. Consequently, the angular error leads to the miscalculation of the polarization coupling intensity. Based on the experimental results, a revised coupling strength calculation equation is proposed to minimize the influence of angular misalignment.
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5.
  • Zhang, Hongxia, et al. (författare)
  • Improved low concentration gas detection system based on intracavity fiber laser
  • 2011
  • Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 82:2, s. 023104-
  • Tidskriftsartikel (refereegranskat)abstract
    • The improvement of a low concentration gas detection system based on the intracavity fiber laser is proposed in this paper. The sensitivity of the system is deduced based on Lambert-Beer law. The optimized system was established with the gas cell made elaborately. In order to apply the wavelength sweeping technique, the fiber Bragg grating reflector was substituted by the wavelength independent Faraday rotation reflector. The sensitivity of the system for acetylene detection is reduced to less than 100 ppm by using the average of three absorption spectra. The acetylene detection coefficients of variation with different concentrations are measured. The gas measurement system is validated to detect low concentration gas effectively.
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6.
  • Zhang, Hongxia, et al. (författare)
  • Mitigation of the birefringence dispersion on the polarization coupling measurement in a long-distance high-birefringence fiber
  • 2012
  • Ingår i: Measurement science and technology. - : IOP Publishing. - 0957-0233 .- 1361-6501. ; 23:2, s. 025203-
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to the birefringence dispersion, the polarization coupling parameter measurement in high-birefringence fiber decreases obviously with the fiber length, especially for long-distance fibers. In this paper, two methods for mitigating the birefringence dispersion in a long-distance fiber are proposed. The first method is a spectral-domain measurement method. The experimental setup and results are described in detail. The other method is a time-domain numerical dispersion compensation algorithm to amend the coupling strength calculation equation. It is based on the fact that the interferogram envelope area is constant even with the existence of birefringence dispersion. The experimental result shows that the time-domain algorithm has high accuracy, and the absolute deviation is less than 1%. The two methods are validated to mitigate the birefringence dispersion in the long-distance high-birefringence fiber effectively.
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7.
  • Chen, Hongxia, et al. (författare)
  • PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation
  • 2024
  • Ingår i: Molecular Cancer Research. - 1541-7786. ; 22:1, s. 94-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells.
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8.
  • Hu, Min, et al. (författare)
  • Suppression of uterine and placental ferroptosis by N-acetylcysteine in a rat model of polycystic ovary syndrome. : Ferroptosis and N-acetylcysteine
  • 2021
  • Ingår i: Molecular human reproduction. - : Oxford University Press (OUP). - 1460-2407 .- 1360-9947. ; 27:12
  • Tidskriftsartikel (refereegranskat)abstract
    • The mechanisms that link hyperandrogenism and insulin resistance to the increased miscarriage rate in women with polycystic ovary syndrome (PCOS) remain elusive. Previous studies demonstrate that increased uterine and placental ferroptosis is associated with oxidative stress-induced fetal loss in a pre-clinical PCOS-like rat model. Here, we investigated the efficacy and molecular mechanism of action of the antioxidant N-acetylcysteine (NAC) in reversing gravid uterine and placental ferroptosis in pregnant rats exposed to 5α-dihydrotestosterone (DHT) and insulin. Molecular and histological analyses showed that NAC attenuated DHT and insulin-induced uterine ferroptosis, including dose-dependent increases in anti-ferroptosis gene content. Changes in other molecular factors after NAC treatment were also observed in the placenta exposed to DHT and insulin, such as increased glutathione peroxidase 4 protein level. Further, increased apoptosis inducing factor mitochondria associated 2 mRNA expression was seen in the placenta but not in the uterus. Additionally, NAC was not sufficient to rescue DHT+insulin-induced mitochondria-morphological abnormalities in the uterus, whereas the same treatment partially reversed such abnormalities in the placenta. Finally, we demonstrated that NAC selectively normalized uterine leukemia inhibitory factor, osteopontin/secreted phosphoprotein 1, progesterone receptor, and homeobox A11 mRNA expression and placental estrogen related receptor beta and trophoblast specific protein alpha mRNA expression. Collectively, our data provide insight into how NAC exerts beneficial effects on differentially attenuating gravid uterine and placental ferroptosis in a PCOS-like rat model with fetal loss. These results indicate that exogenous administration of NAC represents a potential therapeutic strategy in the treatment of hyperandrogenism and insulin resistance-induced uterine and placental dysfunction.
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9.
  • Li, Haimeng, et al. (författare)
  • Sleep microenvironment improvement for the acute plateau entry population through a novel nasal oxygen supply system
  • 2024
  • Ingår i: Building and Environment. - : Elsevier. - 0360-1323 .- 1873-684X. ; 256
  • Tidskriftsartikel (refereegranskat)abstract
    • Most people who have moved to high-altitude areas temporarily suffer from sleep disorders. Sleep deprivation negatively affects not only people's daytime activities but also their health. However, most of the existing nonpharmaceutical intervention methods have the problems of discomfort, restricted movement, or high cost. This study involved the use of an oxygen-rich flow of air in the breathing area during sleep to fight hypoxia and aid with altitude acclimatization when people first traveled to a highland plateau. The associated nasal breathing targeted oxygen supply system (NBTOSS) was designed and optimized by numerical simulation and full-scale experiments. Blood oxygen saturation (SaO2) and pulse rate (PR) monitoring experiments were conducted on subjects exposed to hypoxia at a high altitude (Lhasa, 3646.31 m) with or without assistance from the novel oxygen system and on a lowland plain (Xi'an, 397.5 m) as a comparison. The size of the affected area, concentration target value, and oxygen consumption were used as evaluation indices. Experiments have demonstrated the feasibility of creating an oxygen-enriched microenvironment in breathing area during sleep. The results of the testing showed that the oxygen supply area was uniformly covered and that the degree of hypoxia in subjects was effectively alleviated, with average SaO2 increasing to 95% ± 1%. Maintaining oxygen levels during sleep for temporary residents of high altitudes with less oxygen consumption and minimal oxygen supply costs is discussed to provide a healthy and comfortable oxygen-enriched environment.
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10.
  • Li, Xuemei, et al. (författare)
  • Perfluorooctanesulfonate and related fluorochemicals in the Amur tiger (Panthera tigris altaica) from China
  • 2008
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 42:19, s. 7078-7083
  • Tidskriftsartikel (refereegranskat)abstract
    • Perfluorinated compounds (PFCs) are used in a variety of industrial applications. We tested the hypothesis that, in Amur tigers (Panthera tigris altaica), captivity in industrialized areas increases PFC levels, potentially presenting a health risk to these animals. Serum samples were collected from 100 tigers from industrialized or nonindustrialized regions in China with nonpoint sources of PFCs. Mean concentrations of PFCs in these samples ranged from 1.57 ± 0.83 ng/mL in nonindustrial Hailin to 4.31 ± 2.90 ng/mL in industrial Beijing. PFC concentrations were significantly higher in tigers from the industrial city of Harbin than those from Hailin (p < 0.05). Perfluorooctanesulfonate (PFOS) was the most abundant PFC in all tigers and increased with age, regardless of industrial/nonindustrial background (p < 0.01). However, PFOS concentrations were 2-4 orders of magnitude less than the current no-observed-effect level. In addition, overall PFC levels in Amur tigers were low compared with various species living in other countries, consistent with the relatively short history of PFC use in China. These results are consistent with the hypothesis that captivity in industrialized areas increases PFC levels in Amurtigers. They also suggestthat PFC accumulation will persist, and even increase, with continued use of PFCs in China.
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11.
  • Pan, Yitao, et al. (författare)
  • Associations of urinary 5-methyl-2'-deoxycytidine and 5-hydroxymethyl-2'-deoxycytidine with phthalate exposure and semen quality in 562 Chinese adult men
  • 2016
  • Ingår i: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 94, s. 583-590
  • Tidskriftsartikel (refereegranskat)abstract
    • 5-methyl-2'-deoxycytidine (5mdC) and 5-hydroxymethyl-2'-deoxycytidine (5hmdC), products of DNA methylation and hydroxymethylation processes, have been detected previously in human urine, but their associations with environmental chemicals or healthy outcomes are unclear. The present investigation explored the associations between urinary 5mdC and 5hmdC with phthalate exposure and semen quality. We assessed semen parameters including sperm concentration, motility, and morphology, before measuring urinary 5mdC, 5hmdC and 13 phthalate metabolites among 562 subfertile men from Nanjing, China. Urinary 5mdC and 5hmdC were positively associated with the levels of low molecular weight phthalate metabolites (Low-MWP), high molecular weight phthalate metabolites (High-MWP), and the sum of all phthalate metabolites (ΣPAEs), respectively. Urinary 5mdC was associated with below-reference sperm concentration (odds ratios for increasing quartiles=1.0, 2.2, 3.0, 2.0; p for trend =0.02), sperm motility (1.0, 1.1, 1.9, 1.3; p for trend =0.05), and sperm morphology (1.0, 1.4, 2.3, 1.5; p for trend =0.05). Sperm concentration was associated with the highest quartile of urinary 5hmdC [odds ratio=1.9 (95% CI: 1.1, 3.6)]. Our findings showed significant associations between urinary 5mdC and 5hmdC with phthalate metabolites and semen parameters, which suggested urinary 5mdC and 5hmdC may be promising biomarkers in future epidemiological studies.
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12.
  • Pan, Yitao, et al. (författare)
  • Dietary exposure to di-isobutyl phthalate increases urinary 5-methyl-2'-deoxycytidine level and affects reproductive function in adult male mice
  • 2017
  • Ingår i: Journal of Environmental Sciences(China). - : Elsevier. - 1001-0742 .- 1878-7320. ; 61, s. 14-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Phthalates are a large family of ubiquitous environmental pollutants suspected of being endocrine disruptors. Epidemiological studies have associated phthalate metabolites with decreased reproductive parameters and linked phthalate exposure with the level of urinary 5-methyl-2'-deoxycytidine (5mdC, a product of methylated DNA). In this study, adult male mice were exposed to 450mg di-isobutyl phthalate (DiBP)/(kg·day) via dietary exposure for 28days. Mono-isobutyl phthalate (MiBP, the urinary metabolite) and reproductive function parameters were determined. The levels of 5mdC and 5-hydroxymethyl-2'-deoxycytidine (5hmdC) were measured in urine to evaluate if their contents were also altered by DiBP exposure in this animal model. Results showed that DiBP exposure led to a significant increase in the urinary 5mdC level and significant decreases in sperm concentration and motility in the epididymis, accompanied with reduced testosterone levels and down-regulation of the P450 cholesterol side-chain cleavage enzyme (P450scc) gene in the mice testes. Our findings indicated that exposure to DiBP increased the urinary 5mdC levels, which supported our recent epidemiological study about the associations of urinary 5mdC with phthalate exposure in the male human population. In addition, DiBP exposure impaired male reproductive function, possibly by disturbing testosterone levels; P450scc might be a major steroidogenic enzyme targeted by DiBP or other phthalates.
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13.
  • Pan, Yitao, et al. (författare)
  • First Report on the Occurrence and Bioaccumulation of Hexafluoropropylene Oxide Trimer Acid : An Emerging Concern
  • 2017
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 51:17, s. 9553-9560
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we report on the occurrence of a novel perfluoroalkyl ether carboxylic acid, ammonium perfluoro-2-[(propoxy)propoxy]-1-propanoate (HFPO-TA), in surface water and common carp (Cyprinus carpio) collected from the Xiaoqing River and in 'residents residing near a fluoropolymer production plant in Huantai County, China. Compared with the levels upstream of the Xiaoqing River, HFPO-TA concentrations (5200-68500 ng/L) were approximately 120-1600-times higher downstream after receiving fluoropolymer plant effluent from a tributary. The riverine discharge' of HFPO-TA was estimated to be 4.6 t/yr, accounting for 22% of total PFAS discharge. In the wild common carp collected downstream from the point source, HFPO-TA was detected in the blood (median: 1510 ng/mL), liver (587 ng/g ww), and muscle (118 ng/g ww). The log BCFbiood of HFPO-TA (2.18) was significantly higher than that of PFOA (1.93). Detectable levels of HFPO-TA were also found in the sera of residents (median: 2.93 ng/mL). This is the first report on the environmental occurrence and bioaccumulation of this novel chemical. Our results indicate an emerging usage of HFPO-TA in the fluoropolymer manufacturing industry and raise concerns about the toxicity and potential health risks of HFPO-TA to aquatic organisms and humans.
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14.
  • Pan, Yitao, et al. (författare)
  • Worldwide Distribution of Novel Perfluoroether Carboxylic and Sulfonic Acids in Surface Water
  • 2018
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 52:14, s. 7621-7629
  • Tidskriftsartikel (refereegranskat)abstract
    • Driven by increasingly stringent restrictions on long-chain per- and polyfluoroalkyl substances (PFASs), novel fluorinated compounds have emerged on the market. Here we report on the occurrences of several perfluoroalkyl ether carboxylic and sulfonic acids (PFECAs and PFESAs), including hexafluoropropylene oxide dimer and trimer acids (HFPO-DA and HFPO-TA), ammonium 4,8-dioxa-3 H-perfluorononanoate (ADONA), chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA), and its hydrogen-substituted analogue (6:2 H-PFESA) in surface waters from China ( n = 106), the United States ( n = 12), the United Kingdom ( n = 6), Sweden ( n = 10), Germany ( n = 14), The Netherlands ( n = 6), and Korea ( n = 6). Results showed that HFPO-DA, HFPO-TA, and 6:2 Cl-PFESA (median = 0.95, 0.21, and 0.31 ng/L, respectively) were frequently detected in all countries, indicating ubiquitous dispersal and distribution in global surface waters. The presence of 6:2 H-PFESA was widely detected in China (detection rate > 95%) but not in any other country. Only trace levels of ADONA (0.013-1.5 ng/L) were detected in the Rhine River flowing through Germany. The estimated total riverine mass discharges of HFPO-DA, HFPO-TA, and ΣPFESAs reached 2.6, 6.0, and 4.3 ton/year in five of the major river systems in China. Our results indicated that novel PFECAs and PFESAs might become global contaminants, and future investigations are warranted.
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15.
  • Pilban Jahromi, Siamak, et al. (författare)
  • The effect of supporting electrolyte concentrations on the growth of nickel nanostructures
  • 2021
  • Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388. ; 880
  • Tidskriftsartikel (refereegranskat)abstract
    • Nickel nanostructures (Ni NSs) were grown on poly N-methyl pyrrole (PMPy) surface via facile electrochemical deposition method. Morphology and crystalline properties of the fabricated Ni NSs were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), and cyclic voltammetry (CV). The size-strain plot model was employed to determine the average crystallite sizes of Ni NSs prepared at 0.001, 0.01 and 0.1 M of KCl concentrations, respectively. Results indicated that Ni NSs morphologies were influenced by the concentration of KCl electrolyte in which utilized as supporting electrolyte. The average crystallite size decreased as the KCl electrolyte concentration increased. An irregular structure consisting of microspheres with an average size of 2 µm, nanodendritic structure with an average thickness of 120 nm and a large-scale uniform nanowall structure with an average thickness of 70 nm were formed in the presence of 0.001, 0.01 and 0.1 M KCl concentrations, respectively. The electrochemical behavior of Ni NSs characterized by cyclic voltammetry (CV) in 1 M solution of KOH revealed an improvement in the redox reaction of the Ni nano wall (Ni NW) compared to other Ni NSs electrodes, thus making Ni NW a good candidate for future utilization in electrode materials of fuel cells.
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16.
  • Zhang, Ruyang, et al. (författare)
  • A Large-Scale Genome-Wide Gene-Gene Interaction Study of Lung Cancer Susceptibility in Europeans With a Trans-Ethnic Validation in Asians
  • 2022
  • Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 17:8, s. 974-990
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Although genome-wide association studies have been conducted to investigate genetic variation of lung tumorigenesis, little is known about gene-gene (G × G) interactions that may influence the risk of non-small cell lung cancer (NSCLC).Methods: Leveraging a total of 445,221 European-descent participants from the International Lung Cancer Consortium OncoArray project, Transdisciplinary Research in Cancer of the Lung and UK Biobank, we performed a large-scale genome-wide G × G interaction study on European NSCLC risk by a series of analyses. First, we used BiForce to evaluate and rank more than 58 billion G × G interactions from 340,958 single-nucleotide polymorphisms (SNPs). Then, the top interactions were further tested by demographically adjusted logistic regression models. Finally, we used the selected interactions to build lung cancer screening models of NSCLC, separately, for never and ever smokers.Results: With the Bonferroni correction, we identified eight statistically significant pairs of SNPs, which predominantly appeared in the 6p21.32 and 5p15.33 regions (e.g., rs521828C6orf10 and rs204999PRRT1, ORinteraction = 1.17, p = 6.57 × 10−13; rs3135369BTNL2 and rs2858859HLA-DQA1, ORinteraction = 1.17, p = 2.43 × 10−13; rs2858859HLA-DQA1 and rs9275572HLA-DQA2, ORinteraction = 1.15, p = 2.84 × 10−13; rs2853668TERT and rs62329694CLPTM1L, ORinteraction = 0.73, p = 2.70 × 10−13). Notably, even with much genetic heterogeneity across ethnicities, three pairs of SNPs in the 6p21.32 region identified from the European-ancestry population remained significant among an Asian population from the Nanjing Medical University Global Screening Array project (rs521828C6orf10 and rs204999PRRT1, ORinteraction = 1.13, p = 0.008; rs3135369BTNL2 and rs2858859HLA-DQA1, ORinteraction = 1.11, p = 5.23 × 10−4; rs3135369BTNL2 and rs9271300HLA-DQA1, ORinteraction = 0.89, p = 0.006). The interaction-empowered polygenetic risk score that integrated classical polygenetic risk score and G × G information score was remarkable in lung cancer risk stratification.Conclusions: Important G × G interactions were identified and enriched in the 5p15.33 and 6p21.32 regions, which may enhance lung cancer screening models.
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