| 1. |
- Xie, Yuan, et al.
(författare)
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Wnt signaling regulates MFSD2A-dependent drug delivery through endothelial transcytosis in glioma
- 2023
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 25:6, s. 1073-1084
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Tidskriftsartikel (refereegranskat)abstract
- Background: Systemic delivery of anti-tumor therapeutic agents to brain tumors is thwarted by the blood-brain barrier (BBB), an organotypic specialization of brain endothelial cells (ECs). A failure of pharmacological compounds to cross BBB is one culprit for the dismal prognosis of glioblastoma (GBM) patients. Identification of novel vascular targets to overcome the challenges posed by the BBB in tumors for GBM treatment is urgently needed.Methods: Temozolomide (TMZ) delivery was investigated in CT2A and PDGFB-driven RCAS/tv-a orthotopic glioma models. Transcriptome analysis was performed on ECs from murine gliomas. Mfsd2a deficient, Cav1 deficient, and Mfsd2a EC-specific inducible mice were developed to study the underlying molecular mechanisms.Results: We demonstrated that inhibiting Wnt signaling by LGK974 could increase TMZ delivery and sensitize glioma to chemotherapy in both murine glioma models. Transcriptome analysis of ECs from murine gliomas revealed that Wnt signaling inhibition enhanced vascular transcytosis as indicated by the upregulation of PLVAP and downregulation of MFSD2A. Mfsd2a deficiency in mice enhances TMZ delivery in tumors, whereas constitutive expression of Mfsd2a in ECs suppresses the enhanced TMZ delivery induced by Wnt pathway inhibition in murine glioma. In addition, Wnt signaling inhibition enhanced caveolin-1 (Cav1)-positive caveolae-mediated transcytosis in tumor ECs. Moreover, Wnt signaling inhibitor or Mfsd2a deficiency fails to enhance TMZ penetration in tumors from Cav1-deficient mice.Conclusions: These results demonstrated that Wnt signaling regulates MFSD2A-dependent TMZ delivery through a caveolae-mediated EC transcytosis pathway. Our findings identify Wnt signaling as a promising therapeutic target to improve drug delivery for GBM treatment.
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| 2. |
- Xie, Yuan, et al.
(författare)
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Key molecular alterations in endothelial cells in human glioblastoma uncovered through single-cell RNA sequencing
- 2021
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Ingår i: JCI Insight. - : American Society For Clinical Investigation. - 2379-3708. ; 6:15
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Tidskriftsartikel (refereegranskat)abstract
- Passage of systemically delivered pharmacological agents into the brain is largely blocked by the blood-brain-barrier (BBB), an organotypic specialization of brain endothelial cells (ECs). Tumor vessels in glioblastoma (GBM), the most common malignant brain tumor in humans, are abnormally permeable, but this phenotype is heterogeneous and may differ between the tumor's center and invasive front. Here, through single-cell RNA sequencing (scRNA-seq) of freshly isolated ECs from human glioblastoma and paired tumor peripheral tissues, we have constructed a molecular atlas of human brain ECs providing unprecedented molecular insight into the heterogeneity of the human BBB and its molecular alteration in glioblastoma. We identified 5 distinct EC phenotypes representing different states of EC activation and BBB impairment, and associated with different anatomical locations within and around the tumor. This unique data resource provides key information for designing rational therapeutic regimens and optimizing drug delivery.
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| 3. |
- Yang, Fan, et al.
(författare)
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Uncovering a Distinct Gene Signature in Endothelial Cells Associated With Contrast Enhancement in Glioblastoma
- 2021
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Glioblastoma (GBM) is the most aggressive and lethal type of brain tumors. Magnetic resonance imaging (MRI) has been commonly used for GBM diagnosis. Contrast enhancement (CE) on T1-weighted sequences are presented in nearly all GBM as a result of high vascular permeability in glioblastomas. Although several radiomics studies indicated that CE is associated with distinct molecular signatures in tumors, the effects of vascular endothelial cells, the key component of blood brain barrier (BBB) controlling vascular permeability, on CE have not been thoroughly analyzed. Methods Endothelial cell enriched genes have been identified using transcriptome data from 128 patients by a systematic method based on correlation analysis. Distinct endothelial cell enriched genes associated with CE were identified by analyzing difference of correlation score between CE-high and CE-low GBM cases. Immunohistochemical staining was performed on in-house patient cohort to validate the selected genes associated with CE. Moreover, a survival analysis was conducted to uncover the relation between CE and patient survival. Results We illustrated that CE is associated with distinct vascular molecular imprints characterized by up-regulation of pro-inflammatory genes and deregulation of BBB related genes. Among them, PLVAP is up-regulated, whereas TJP1 and ABCG2 are down-regulated in the vasculature of GBM with high CE. In addition, we found that the high CE is associated with poor prognosis and GBM mesenchymal subtype. Conclusion We provide an additional insight to reveal the molecular trait for CE in MRI images with special focus on vascular endothelial cells, linking CE with BBB disruption in the molecular level. This study provides a potential new direction that may be applied for the treatment optimization based on MRI features.
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| 4. |
- Deng, Xiangyi, et al.
(författare)
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ECO : An Integrated Gene Expression Omnibus for Mouse Endothelial Cells In Vivo
- 2022
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Ingår i: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial cell (EC) plays critical roles in vascular physiological and pathological processes. With the development of high-throughput technologies, transcriptomics analysis of EC has increased dramatically and a large amount of informative data have been generated. The dynamic patterns of gene expression in ECs under various conditions were revealed. Unfortunately, due to the lack of bioinformatics infrastructures, reuse of these large-scale datasets is challenging for many scientists. Here, by systematic re-analyzing, integrating, and standardizing of 203 RNA sequencing samples from freshly isolated mouse ECs under 71 conditions, we constructed an integrated mouse EC gene expression omnibus (ECO). The ECO database enables one-click retrieval of endothelial expression profiles from different organs under different conditions including disease models, genetic modifications, and clinically relevant treatments in vivo. The EC expression profiles are visualized with user-friendly bar-plots. It also provides a convenient search tool for co-expressed genes. ECO facilitates endothelial research with an integrated tool and resource for transcriptome analysis. The ECO database is freely available at https://heomics. shinyapps.io/ecodb/.
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| 5. |
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| 6. |
- Gong, Chensheng, et al.
(författare)
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Hybrid unidirectional meta-coupler for vertical incidence to a high-refractive-index waveguide in telecom wavelength
- 2017
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Ingår i: Optics Letters. - : OPTICAL SOC AMER. - 0146-9592 .- 1539-4794. ; 42:24, s. 5098-5101
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Tidskriftsartikel (refereegranskat)abstract
- Unidirectional optical manipulation, especially the coupling from a vertical light beam to a waveguide unidirectionally, is desirable in photonic integration. We first propose a hybrid unidirectional meta-coupler for vertical incidence to a high-refractive-index waveguide in telecom wavelength, a periodic plasmonic metasurface composed of metal-insulator-metal unit cells is used for phase matching. Three designs are given for devices working around wavelengths 0.85, 1.31, and 1.55 mu m. The simulated coupling efficiencies are all around 70%, and the 1 dB coupling bandwidths are 29, 82, and 105 nm, respectively. Our approach paves the way for the applications of optical metasurfaces to planar lightwave circuits. (C) 2017 Optical Society of America
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| 7. |
- Peng, Jianhao, et al.
(författare)
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Deep Reinforcement Learning for Energy-Efficient Power Control in Heterogeneous Networks
- 2022
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Ingår i: ICC 2022 - IEEE International Conference on Communications. - : IEEE. ; , s. 141-146
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Konferensbidrag (refereegranskat)abstract
- In a typical heterogeneous network (HetNet), in which a macro base station (BS) and multiple small BSs coexist on the same spectrum band, energy-efficiency (EE) performance is an important design metric and is highly related to the transmit power of BSs. Conventional methods optimize BSs' transmit power to enhance the EE by assuming that the global channel state information (CSI) is available. However, it is challenging or expensive to collect the instantaneous global CSI in the HetNet. In this paper, we utilize deep reinforcement learning (DRL) technique to design an intelligent power control algorithm, with which each BS can independently determine the transmit power based on only local information. Simulation results demonstrate that the proposed algorithm outperforms conventional methods in terms of both EE performance and time complexity.
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| 8. |
- Peng, Jianhao, et al.
(författare)
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Lightweight Cloud-Edge Collaborations for Intelligent Power Control in Energy-Efficient Heterogeneous Networks
- 2023
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Ingår i: GLOBECOM 2023 - 2023 IEEE Global Communications Conference. - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 7007-7012
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Konferensbidrag (refereegranskat)abstract
- This paper studies the global energy efficiency (GEE) optimization problem in a typical heterogeneous network (HetNet), where a macro base station (BS) and multiple micro BSs share the same spectrum band. Conventional optimization methods typically involve collecting global instantaneous channel state information (CSI) and utilizing centralized optimization algorithms to obtain the optimal transmit power and enhance the GEE. However, it is expensive to obtain the global instantaneous CSI in practical scenarios, and the optimization algorithms tend to be time-consuming. In this paper, we develop a lightweight cloud-edge collaboration framework based on the deep reinforcement learning (DRL) technique, such that the BSs in the edge do not need to exchange local instantaneous information with each other, and the core network in the cloud can collect only historical data rates and energy consumption information from each edge BS and feeds the calculated global reward back to them. Within the frame-work, we establish an independent actor-critic structure for each BS, and design a multi-agent independent actor-critic (MAIAC) power control algorithm, which enables each BS to determine its transmit power locally and enhance the GEE based on only local information. Simulation results indicate that the proposed MAIAC algorithm can achieve comparable GEE performance with conventional algorithms while requiring significantly less time complexity.
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| 9. |
- Wang, Jianhao, et al.
(författare)
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An Integrated Transcriptome Analysis Reveals IGFBP7 Upregulation in Vasculature in Traumatic Brain Injury
- 2021
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Ingår i: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Vasculature plays critical roles in the pathogenesis and neurological repair of traumatic brain injury (TBI). However, how vascular endothelial cells respond to TBI at the molecular level has not been systematically reviewed. Here, by integrating three transcriptome datasets including whole cortex of mouse brain, FACS-sorted mouse brain endothelial cells, and single cell sequencing of mouse brain hippocampus, we revealed the key molecular alteration of endothelial cells characterized by increased Myc targets and Epithelial-Mesenchymal Transition signatures. In addition, immunofluorescence staining of patients' samples confirmed that IGFBP7 was up-regulated in vasculature in response to TBI. TGF beta 1, mainly derived from microglia and endothelial cells, sufficiently induces IGFBP7 expression in cultured endothelial cells, and is significantly upregulated in response to TBI. Our results identified IGFBP7 as a potential biomarker of vasculature in response to TBI, and indicate that TGF beta signaling may contribute to the upregulation of IGFBP7 in the vasculature.
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| 10. |
- Wang, Nan, et al.
(författare)
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Lasing properties of a cholesteric liquid crystal containing aggregation-induced-emission material
- 2015
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Ingår i: Optics Express. - : Optical Society of America. - 1094-4087. ; 23:26, s. 33938-33946
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate band edge lasing action from a cholesteric liquid crystal (CLC) containing an aggregation-induced-emission (AIE) dye as gain material. AIE materials do not suffer aggregation-caused quenching, have strong resistance to photobleaching, and can show large Stokes shift. The amplified spontaneous emission (ASE) and lasing emission of the dye-doped CLC cell have been characterized, the lasing threshold has been estimated, and its resistance to photobleaching has been measured. AIE materials with their unique properties are especially suitable for acting as gain materials in liquid crystal lasers where defect structures lower the threshold for nanoscale aggregation effects. Our studies have shown that such AIE-dye-doped CLC is capable of lasing action with unusually large Stokes shift at moderate threshold with strong resistance to photobleaching.
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