| 1. |
- Lee, Chunsik, et al.
(författare)
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VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway
- 2023
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Ingår i: SIGNAL TRANSDUCTION AND TARGETED THERAPY. - : SPRINGERNATURE. - 2095-9907 .- 2059-3635. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.
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| 2. |
- Chen, Zhen, et al.
(författare)
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Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a "Tail Switching" Strategy on a Piperazinyl Azetidine Skeleton
- 2019
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 62:7, s. 3336-3353
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Tidskriftsartikel (refereegranskat)abstract
- Monoacylglycerol lipase (MAGL) is a senile hydrolase that degrades 2-arachidonoylglycerol (2-AG) in the endocannabinoid system (eCB). Selective inhibition of MAGL has emerged as a potential therapeutic approach for the treatment of diverse pathological conditions, including chronic pain, inflammation, cancer, and neurodegeneration. Herein, we disclose a novel array of reversible and irreversible MAGL inhibitors by means of "tail switching" on a piperazinyl azetidine scaffold. We developed a lead irreversible-binding MAGL inhibitor 8 and reversible-binding compounds 17 and 37, which are amenable for radiolabeling with C-11 or F-18. [C-11]8 ([C-11]MAGL-2-11) exhibited high brain uptake and excellent binding specificity in the brain toward MAGL. Reversible radioligands [C-11]17 ([C-11]PAD) and [F-18]37 ([F-18]MAGL-4-11) also demonstrated excellent in vivo binding specificity toward MAGL in peripheral organs. This work may pave the way for the development of MAGL-targeted positron emission tomography tracers with tunability in reversible and irreversible binding mechanisms.
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| 3. |
- Liu, Zhixi, et al.
(författare)
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The burden of hand, foot, and mouth disease among children under different vaccination scenarios in China: a dynamic modelling study
- 2021
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common illness in young children. A monovalent vaccine has been developed in China protecting against enterovirus-71, bivalent vaccines preventing HFMD caused by two viruses are under development.OBJECTIVE: To predict and compare the incidence of HFMD under different vaccination scenarios in China.METHODS: We developed a compartmental model to capture enterovirus transmission and the natural history of HFMD in children aged 0-5, and calibrated to reported cases in the same age-group from 2015 to 2018. We compared the following vaccination scenarios: different combinations of monovalent and bivalent vaccine; a program of constant vaccination to that of pulse vaccination prior to seasonal outbreaks.RESULTS: We estimate 1,982,819, 2,258,846, 1,948,522 and 2,398,566 cases from 2015 to 2018. Increased coverage of monovalent vaccine from 0 to 80% is predicted to decrease the cases by 797,262 (49.1%). Use of bivalent vaccine at an 80% coverage level would decrease the cases by 828,560. Use of a 2.0× pulse vaccination for the bivalent vaccine in addition to 80% coverage would reduce cases by over one million. The estimated R0 for HFMD in 2015-2018 was 1.08, 1.10, 1.35 and 1.17.CONCLUSIONS: Our results point to the benefit of bivalent vaccine and using a pulse vaccination in specific months over routine vaccination. Other ways to control HFMD include isolation of patients in the early stage of dissemination, more frequent hand-washing and ventilation, and better treatment options for patients.
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| 4. |
- Xiong, Shaobing, et al.
(författare)
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Direct Observation on p- to n-Type Transformation of Perovskite Surface Region during Defect Passivation Driving High Photovoltaic Efficiency
- 2021
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Ingår i: Joule. - : CELL PRESS. - 2542-4351. ; 5:2, s. 467-480
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Tidskriftsartikel (refereegranskat)abstract
- Perovskite solar cells (PSCs) suffer from significant nonradiative recombination, limiting their power conversion efficiencies. Here, for the first time, we directly observe a complete transformation of perovskite MAPbI(3) surface region energetics from p- to n-type during defect passivation caused by natural additive capsaicin, attributed to the spontaneous formation of a p-n homojunction in perovskite active layer. We demonstrate that the p-n homojunction locates at similar to 100 nm below perovskite surface. The energetics transformation and defect passivation promote charge transport in bulk perovskite layer and at perovskite/PCBM interface, suppressing both defect-assisted recombination and interface carrier recombination. As a result, an efficiency of 21.88% and a fill factor of 83.81% with excellent device stability are achieved, both values are the highest records for polycrystalline MAPbI(3) based p-i-n PSCs reported to date. The proposed new concept of synergetic defect passivation and energetic modification via additive provides a huge potential for further improvement of PSC performance.
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| 5. |
- Yang, Jianming, et al.
(författare)
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Energetics and Energy Loss in 2D Ruddlesden-Popper Perovskite Solar Cells
- 2020
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Ingår i: Advanced Energy Materials. - : WILEY-V C H VERLAG GMBH. - 1614-6832 .- 1614-6840. ; 10:23
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Tidskriftsartikel (refereegranskat)abstract
- 2D Ruddlesden-Popper perovskites (RPPs) are emerging as potential challengers to their 3D counterpart due to superior stability and competitive efficiency. However, the fundamental questions on energetics of the 2D RPPs are not well understood. Here, the energetics at (PEA)(2)(MA)(n)-1PbnI3n+1/[6,6]-phenyl-C61-butyric acid methyl ester (PCBM) interfaces with varying n values of 1, 3, 5, 40, and infinity are systematically investigated. It is found that n-n junctions form at the 2D RPP interfaces (n = 3, 5, and 40), instead of p-n junctions in the pure 2D and 3D scenarios (n = 1 and infinity). The potential gradient across phenethylammonium iodide ligands that significantly decreases surface work function, promotes separation of the photogenerated charge carriers with electron transferring from perovskite crystal to ligand at the interface, reducing charge recombination, which contributes to the smallest energy loss and the highest open-circuit voltage (V-oc) in the perovskite solar cells (PSCs) based on the 2D RPP (n = 5)/PCBM. The mechanism is further verified by inserting a thin 2D RPP capping layer between pure 3D perovskite and PCBM in PSCs, causing the V-oc to evidently increase by 94 mV. Capacitance-voltage measurements with Mott-Schottky analysis demonstrate that such V-oc improvement is attributed to the enhanced potential at the interface.
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