| 1. |
- Xie, Xu-Qin, et al.
(författare)
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miR-124 Intensified Oxaliplatin-Based Chemotherapy by Targeting CAPN2 in Colorectal Cancer
- 2020
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Ingår i: MOLECULAR THERAPY-ONCOLYTICS. - : CELL PRESS. - 2372-7705. ; 17, s. 320-331
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Tidskriftsartikel (refereegranskat)abstract
- Our previous study demonstrated that miR-124 was downregulated in colorectal cancer (CRC) compared with normal mucosa, and the downregulated expression of miR-124 was an independent prognostic factor in CRC patients. However, the function of miR-124 in CRC patients treated with chemotherapy is currently unclear. The aim of this study was to determine the miR-124 expression and its regulative role in oxaliplatin (L-OHP)-based chemotherapy of CRC patients. We observed that low miR-124 expression was correlated with worse overall survival (OS) in the 220 patients who received postoperative chemotherapy of 5-fluorouracil [5-FU] +leucovorin+L-OHP (FOLFOX) or capecitabine+L-OHP (XELOX). miR-124 overexpression promoted L-OHP-induced, but not 5-FU-induced, cytotoxicity and apoptosis in HT29 and SW480 cells. CAPN2 was a direct target of miR124, and its protein expression was reduced by forced expression of miR-124. miR-124 inhibited tumorigenesis and promoted OS of mice bearing xenograft tumors, especially upon L-OHP treatment. miR-124 also promoted L-OHP-induced apoptosis and restrained CAPN2 protein expression in xenograft tumors. Our results suggest that miR-124 could be considered as both a predictor of L-OHP-based chemotherapy for personalized treatment and a therapeutic target for CRC.
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| 2. |
- Yaghootkar, Hanieh, et al.
(författare)
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Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity
- 2020
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 69:12, s. 2806-2818
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Tidskriftsartikel (refereegranskat)abstract
- Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.
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| 3. |
- Zhang, Jiliang, et al.
(författare)
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Generalized Polarization-Space Modulation
- 2020
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Ingår i: IEEE Transactions on Communications. - 0090-6778 .- 1558-0857. ; 68:1, s. 258-273
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Tidskriftsartikel (refereegranskat)abstract
- A novel generalized polarization-space modulation (GPSM) is proposed for polarized multiple-input multiple-output (MIMO) systems with a limit number of radio frequency (RF) chains. In the spatial domain, multiple dual-polarized (DP) transmit antennas are activated, and then combinations of those indices are used to convey information. While in the polarization domain, depending on the random input bits, only one polarization state is selected for each active DP transmit antenna to transmit information following the rule of the polarized shift keying. At the receiver, the maximum likelihood detector is employed as a benchmark to detect information bits being used to select the polarization state and activated DP antennas. In the detector, imperfect channel state information (CSI) is taken into account. Two less computationally complex detectors, i.e., a linear detector and a sphere decoding (SD) detector are proposed to relieve the computational burden. Sacrificing the average bit error probability (ABEP) performance, the proposed linear detector can reduce the computational complexity significantly. The proposed SD detector can achieve the optimum ABEP performance, while reducing computational complexity by reducing the search space. A closed-form union upper bound (UUB) on the ABEP of the GPSM system with imperfect CSI at the receiver is analytically derived and validated through simulations. From the UUB, a loose asymptotic bound on the ABEP, which sheds light on deriving the diversity gain and the coding gain, is derived. Numerical results show that the signal-to-noise ratio loss caused by increasing the number of transmit antennas is less than 3 dB while the spectral efficiency is increased by 7 b/z/Hz. Therefore, the GPSM can be a promising candidate of down link massive MIMO systems to achieve a high spectral efficiency with a limit number of RF chains.
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