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Sökning: WFRF:(Zhang Kexin)

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1.
  • Li, Ao, et al. (författare)
  • Genome architecture and selective signals compensatorily shape plastic response to a new environment
  • 2023
  • Ingår i: The Innovation. - 2666-6758. ; 4:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Transcriptional plasticity interacts with natural selection in complex ways and is crucial for the survival of species under rapid climate change. How 3D genome architecture affects transcriptional plasticity and its interaction with genetic adaptation are unclear. We transplanted estuarine oysters to a new environment and found that genes located in active chromatin regions exhibited greater transcriptional plasticity, and changes in these regions were negatively correlated with selective signals. This indicates a trade-off be- tween 3D active regions and selective signals in shaping plastic responses to a new environment. Specifically, a mutation, lincRNA, and changes in the accessibility of a distal enhancer potentially affect its interaction with the ManIIa gene, which regulates the muscle function and survival of oysters. Our findings reveal that 3D genome architecture compensates for the role of genetic adaptation in environmental response to new environments and provide insights into synergetic genetic and epigenetic interactions critical for fitness-related trait and survival in a model marine species.
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2.
  • Sampson, Joshua N., et al. (författare)
  • Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
  • 2015
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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3.
  • Wang, Kui, et al. (författare)
  • Efficient electro-demulsification of O/W emulsions and simultaneous oil removal enabled by a multiscale porous biocarbon electrode
  • 2024
  • Ingår i: Chemical Engineering Journal. - : Elsevier BV. - 1385-8947 .- 1873-3212. ; 481
  • Tidskriftsartikel (refereegranskat)abstract
    • Emulsion wastewater contain substantial amounts of oil and various additives, which pose threats to the environment and human health. Demulsification is a crucial pretreatment stage for wastewater. This study aims to identify a novel electro-demulsification method with high oil removal efficiency and low energy consumption. Modified carbonized birch wood with a unique isotropic multiscale pore structure is used as a self-standing electrode to treat a toluene oil-in-water (O/W) emulsion. The electrode must have a highly porous structure to facilitate efficient water diffusion and oil adsorption. It must also have high electronic conductivity to expedite polarized molecular electrophoresis to realize penetration into the pores and, subsequently, demulsification. Guided by an applied electric field force, polarized O/W droplets are drawn toward the electrode, revealing electrical characteristics distinct from those of polarized organic molecules. This electric field force augments the capture and adhesion of droplets by the electric double layer at the electrode interface. Consequently, adsorbed droplets in close proximity to the electrode rupture due to the combined influence of the electric field force and the electrostatic effects stemming from the electrode's multiscale porous structure. This synergistic action enables demulsification to occur efficiently at low energy consumption levels. This study has revealed that electro-demulsification can effectively treat toluene emulsions stabilized by various surfactants and microemulsion containing toluene. Therefore, this electro-demulsification technology can be further developed for various types of water pollution.
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4.
  • Yamamoto, Io, et al. (författare)
  • Telomeric double-strand DNA-binding proteins DTN-1 and DTN-2 ensure germline immortality in Caenorhabditis elegans.
  • 2021
  • Ingår i: eLife. - 2050-084X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Telomeres are nucleoprotein complexes at the ends of chromosomes and are indispensable for the protection and lengthening of terminal DNA. Despite the evolutionarily conserved roles of telomeres, the telomeric double-strand DNA (dsDNA)-binding proteins have evolved rapidly. Here, we identified double-strand telomeric DNA-binding proteins (DTN-1 and DTN-2) in Caenorhabditis elegans as non-canonical telomeric dsDNA-binding proteins. DTN-1 and DTN-2 are paralogous proteins that have three putative MYB-like DNA-binding domains and bind to telomeric dsDNA in a sequence-specific manner. DTN-1 and DTN-2 form complexes with the single-strand telomeric DNA-binding proteins POT-1 and POT-2 and constitutively localize to telomeres. The dtn-1 and dtn-2 genes function redundantly, and their simultaneous deletion results in progressive germline mortality, which accompanies telomere hyper-elongation and chromosomal bridges. Our study suggests that DTN-1 and DTN-2 are core shelterin components in C. elegans telomeres that act as negative regulators of telomere length and are essential for germline immortality.
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5.
  • Zhang, Jingjing, 1986, et al. (författare)
  • The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs the mitotic BRCA2-RAD51 function in cancer cells.
  • 2020
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast cancer susceptibility gene II (BRCA2) is central in homologous recombination (HR). In meiosis, BRCA2 binds to MEILB2 to localize to DNA double-strand breaks (DSBs). Here, we identify BRCA2 and MEILB2-associating protein 1 (BRME1), which functions as a stabilizer of MEILB2 by binding to an α-helical N-terminus of MEILB2 and preventing MEILB2 self-association. BRCA2 binds to the C-terminus of MEILB2, resulting in the formation of the BRCA2-MEILB2-BRME1 ternary complex. In Brme1 knockout (Brme1-/-) mice, the BRCA2-MEILB2 complex is destabilized, leading to defects in DSB repair, homolog synapsis, and crossover formation. Persistent DSBs in Brme1-/- reactivate the somatic-like DNA-damage response, which repairs DSBs but cannot complement the crossover formation defects. Further, MEILB2-BRME1 is activated in many human cancers, and somatically expressed MEILB2-BRME1 impairs mitotic HR. Thus, the meiotic BRCA2 complex is central in meiotic HR, and its misregulation is implicated in cancer development.
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6.
  • Cai, Demin, et al. (författare)
  • Co-option of PPARα in the regulation of lipogenesis and fatty acid oxidation in CLA-induced hepatic steatosis
  • 2021
  • Ingår i: Journal of Cellular Physiology. - : Wiley. - 0021-9541 .- 1097-4652. ; 236:6, s. 4387-4402
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonalcoholic-fatty-liver-disease (NAFLD) is the result of imbalances in hepatic lipid partitioning and is linked to dietary factors. We demonstrate that conjugated linoleic acid (CLA) when given to mice as a dietary supplement, induced an enlarged liver, hepatic steatosis, and increased plasma levels of fatty acid (FA), alanine transaminase, and triglycerides. The progression of NAFLD and insulin resistance was reversed by GW6471 a small-molecule antagonist of peroxisome proliferator-activated receptor α (PPARα). Transcriptional profiling of livers revealed that the genes involved in FA oxidation and lipogenesis as two core gene programs controlled by PPARα in response to CLA and GW6471 including Acaca and Acads. Bioinformatic analysis of PPARα ChIP-seq data set and ChIP-qPCR showed that GW6471 blocks PPARα binding to Acaca and Acads and abolishes the PPARα-mediated local histone modifications of H3K27ac and H3K4me1 in CLA-treated hepatocytes. Thus, our findings reveal a dual role of PPARα in the regulation of lipid homeostasis and highlight its druggable nature in NAFLD.
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7.
  • Han, Fang, et al. (författare)
  • Steppe development on the Northern Tibetan Plateau inferred from Paleogene ephedroid pollen
  • 2016
  • Ingår i: Grana. - : Informa UK Limited. - 0017-3134 .- 1651-2049. ; 55:1, s. 71-100
  • Tidskriftsartikel (refereegranskat)abstract
    • Steppe vegetation represents a key marker of past Asian aridification and is associated with monsoonal intensification. Little is, however, known about the origin of this pre-Oligocene vegetation, its specific composition and how it changed over time and responded to climatic variations. Here, we describe the morphological characters of Ephedraceae pollen in Eocene strata of the Xining Basin and compare the pollen composition with the palynological composition of Late Cretaceous and Paleocene deposits of the Xining Basin and the Quaternary deposits of the Qaidam Basin. We find that the Late Cretaceous steppe was dominated by Gnetaceaepollenites; in the transition from the Cretaceous to the Paleocene, Gnetaceaepollenites became extinct and Ephedripites subgenus Ephedripites dominated the flora with rare occurrences of Ephedripites subgen. Distachyapites; the middle to late Eocene presents a strong increase of Ephedripites subgen. Distachyapites; and the Quaternary/Recent is marked by a significantly lower diversity of Ephedraceae (and Nitrariaceae) compared to the Eocene. In the modern landscape of China, only a fraction of the Paleogene species diversity of Ephedraceae remains and we propose that these alterations in Ephedreaceae composition occurred in response to the climatic changes at least since the Eocene. In particular, the strong Eocene monsoons that enhanced the continental aridification may have played an important role in the evolution of Ephedripites subgen. Distachyapites triggering an evolutionary shift to wind-pollination in this group. Conceivably, the Ephedraceae/Nitrariaceae dominated steppe ended during the Eocene/Oligocene climatic cooling and aridification, which favoured other plant taxa.
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8.
  • Liu, Kexin, et al. (författare)
  • 100 Gbit/s THz Photonic Wireless Transmission in the 350-GHz Band With Extended Reach
  • 2018
  • Ingår i: IEEE Photonics Technology Letters. - : Institute of Electrical and Electronics Engineers (IEEE). - 1041-1135 .- 1941-0174. ; 30:11, s. 1064-1067
  • Tidskriftsartikel (refereegranskat)abstract
    • In this letter, we experimentally demonstrate terahertz (THz) photonic wireless transmission of high-speed quadrature-phase-shift-keying (QPSK) and 16 quadrature amplitude modulation (16-QAM) signals in the 350-GHz band, with an effort to extend the wireless reach of ultrafast 100 Gbit/s. In the experiment, a narrowband unitraveling-carrier photodiode (UTC-PD) is used for heterodyne generation of THz communication signals, which is transparent to optical modulation formats. Experimental results show that 30 GBd/s QPSK (60 Gbit/s) and 25 GBd/s 16-QAM signals (100 Gbit/s) are successfully transmitted over a 350-GHz wireless link with an extended distance of 2 m. This enhancement is enabled by combining the techniques of employing cutting-edge narrowband UTC-PD as the photomixing THz emitter, spectrally efficient modulation format and advanced digital signal processing algorithms. The achievement makes 100 Gbit/s THz wireless communication systems promising for future smart wireless services.
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9.
  • Liu, Kexin, et al. (författare)
  • Enhanced Accessibility of 350 GHz 100 Gbit/s 16-QAM Photonic Wireless Link
  • 2018
  • Ingår i: Proceedings 11th UK-Europe-China Workshop on Millimetre-Waves and Terahertz Technologies (UCMMT) Vol 1. - : Institute of Electrical and Electronics Engineers (IEEE).
  • Konferensbidrag (refereegranskat)abstract
    • We experimentally demonstrate an ultrafast terahertz (THz) photonic wireless communication link in the 350 GHz band with up to 100 Gbit/s data rate, with an emphasis on extending its wireless reach. By combining the techniques of using a cutting-edge narrow-band uni-traveling-carrier photodiode (UTC-PD) as the THz photo-mixing emitter, spectrally efficient modulation formats and advanced digital signal processing (DSP) algorithms, we successfully transmit 25 GBaud/s 16-quadrature amplitude modulation (16-QAM) signals (overall 100 Gbit/s data rate) over a 350 GHz wireless link with an extended distance of 2 m. This achievement pushes the accessibility of ultrafast 100 Gbit/s wireless communication beyond the state-of-the-art, and makes 100 Gbit/s ultrafast THz wireless communication systems promising for future smart high speed wireless access services.
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10.
  • Wang, Ke, et al. (författare)
  • Shadow prices of direct and overall carbon emissions in China's construction industry : A parametric directional distance function-based sensitive estimation
  • 2018
  • Ingår i: Structural Change and Economic Dynamics. - : ELSEVIER SCIENCE BV. - 0954-349X .- 1873-6017. ; 47, s. 180-193
  • Tidskriftsartikel (refereegranskat)abstract
    • Construction industry, together with building materials industries supplying it, is one of China's largest emitters of CO2. Structural change in construction industry has been promoted to mitigate CO2. This paper estimates CO2 shadow price of construction industry and its supporting materials industries in China so as to help them to mitigate CO2 cost-effectively. A parametric directional distance function model, taking into account all possible directional vectors, is applied to address issues regarding arbitrary selection of direction that will affect estimation of shadow price. Results show that there is larger potential for CO2 reduction in supporting material industries than in construction industry itself and shadow price of overall CO2 is much lower than that of direct CO2. The existence of enlarging heterogeneity in shadow prices among different regions provides strong support for introducing a national carbon trading market, thereby helping construction industry and building materials industries to reduce their abatement costs.
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11.
  • Yao, Defan, et al. (författare)
  • Molecular Engineered Squaraine Nanoprobe for NIR-II/Photoacoustic Imaging and Photothermal Therapy of Metastatic Breast Cancer
  • 2020
  • Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 12:4, s. 4276-4284
  • Tidskriftsartikel (refereegranskat)abstract
    • Various squaraine dyes have been developed for biological imaging. Nevertheless, squaraine dyes with emission in the second window (NIR-II, 1000-1700 nm) have few reports largely due to the short of a simple and universal design strategy. In this contribution, molecular engineering strategy is explored to develop squaraine dyes with NIR-II emission. First, NIR-I squaraine dye SQ2 is constructed by the ethyl-grafted 1,8-naphtholactam as donor units and square acid as acceptor unit in a donor-acceptor-donor (D-A-D) structure. To red-shift the fluorescence emission into NIR-II window, malonitrile, as a forceful electron-withdrawing group, is introduced to strengthen square acid acceptor. As a result, the fluorescence spectrum of acceptor-engineered squaraine dye SQ1 exhibits a significant red- shift into NIR-II window. To translate NIR-II fluorophores SQ1 into effective theranostic agents, fibronectin-targeting SQ1 nanoprobe was constructed and showed excellent NIR-II imaging performance in angiography and tumor imaging, including lung metastatic foci in deep tissue. Furthermore, SQ1 nanoprobe can be used for photoacoustic imaging and photothermal ablation of tumors. This research demonstrates that the donor-acceptor engineering strategy is feasible and effective to develop NIR-II squaraine dyes.
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12.
  • Zhang, Kexin, 1993 (författare)
  • Preserving Genetic Integrity in Reproduction: Insights from Telomere Protection and Sperm Head-Tail Junctions
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This doctoral thesis embarks on a meticulous exploration of genetic integrity within the expansive domain of reproductive biology. Its overarching objective is to decipher the intricacies that underlie the preservation of hereditary stability across generations. This multifaceted inquiry transcends the mere conservation of telomere integrity and delves into the intricate roles played by sperm head-tail junctions. These elements are integral in orchestrating the precise management of genetic information throughout the complex journey of reproduction. Paper I: This thesis begins by investigating the integral role of the protein MC2 (Male germ cell-upregulated coiled-coil domain-containing protein 2) in anchoring sperm heads to their tails, a pro-cess crucial for maintaining the integrity of male germ cells during spermiogenesis. The role of MC2 dysfunction in male sterility is significant, particularly in the context of its involvement in the rigid assembly of the head-to-tail coupling apparatus (HTCA). Our findings indicate that in the absence of functional MC2 protein, the HTCA region becomes disconnected from the nucleus, specifically during the elongation phase of spermatids. This disconnection leads to the production of acephalic spermatozoa and results in male sterility. As we shift our focus from the defects in spermiogenesis that cause male infertility to the earlier stage of spermatogenesis, specifically meiosis, we further reinforce the theme of maintaining genetic integrity throughout the reproductive process. Paper II: Building upon this foundation, we delve into the meiosis-specific telomere protein TERB1 that anchors telomeres to the nuclear envelope and facilitates the pairing of homologous chromo-somes. We found that although TERB1 has an MYB-like DNA-binding domain, it doesn't have the typical DNA-binding activity. Furthermore, the MYB domain of TERB1 is not necessary for telomere localization, homologous pairing, or fertility, but it does regulate the enrichment of cohesin and promotes the remodeling of axial elements. This function of the TERB1 MYB domain is likely crucial for maintaining telomeric DNA and genomic integrity by preventing meiotic telomere erosion over long evolutionary timescales. Paper III: Shifting focus from the previous mouse animal model to the Caenorhabditis elegans model, we elucidate the roles of double-stranded telomeric DNA-binding proteins DTN-1 and DTN-2, which also have MYB-like DNA-binding domains, in ensuring germline immortality in C. elegans. C. elegans, with its short lifespan and amenability to in vivo experimentation, provides a valuable animal model for understanding the protection of genetic material across generations. Keywords: Reproductive biology, Sperm head-tail junctions, HTCA, Telomeric DNA-binding proteins, TERB1, MYB domain, DTN-1 and DTN-2
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