| 1. |
- Li, Peng, et al.
(författare)
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Transcriptional reactivation of OTX2, RX1 and SIX3 during reprogramming contributes to the generation of RPE cells from human iPSCs
- 2016
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Ingår i: International Journal of Biological Sciences. - : Ivyspring International Publisher. - 1449-2288. ; 12:5, s. 505-517
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Tidskriftsartikel (refereegranskat)abstract
- Directed differentiation of human induced pluripotent stem cells (iPSCs) into retinal pigmented epithelium (RPE) holds great promise in cell replacement therapy for patients suffering from degenerative eye diseases, including age-related macular degeneration (AMD). In this study, we generated iPSCs from human dermal fibroblasts (HDFs) by electroporation with episomal plasmid vectors encoding OCT4, SOX2, KLF4, L-MYC together with p53 suppression. Intriguingly, cell reprogramming resulted in a metastable transcriptional activation and selective demethylation of neural and retinal specification-associated genes, such as OTX2, RX1 and SIX3. In contrast, RPE progenitor genes were transcriptionally silent in HDFs and descendant iPSCs. Overexpression of OCT4 and SOX2 directly stimulated the expression of OTX2, RX1 and SIX3 in HDFs and iPSCs. Luciferase and chromatin immunoprecipitation (ChIP) assays further identified an OCT4- and two SOX2-binding sites located in the proximal promoter of OTX2. Histone acetylation and methylation on the local promoter also participated in the reactivation of OTX2. The transcriptional conversion of RX1 and SIX3 genes partially attributed to DNA demethylation. Subsequently, iPSCs were induced into the RPE cells displaying the characteristics of polygonal shapes and pigments, and expressing typical RPE cell markers. Taken together, our results establish readily efficient and safe protocols to produce iPSCs and iPSC-derived RPE cells, and underline that the reactivation of anterior neural transcription factor OTX2, eye field transcription factor RX1 and SIX3 in iPSCs is a feature of pluripotency acquisition and predetermines the potential of RPE differentiation.
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| 2. |
- Feng, Ruizhi, et al.
(författare)
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Mutations in TUBB8 and Human Oocyte Meiotic Arrest.
- 2016
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Ingår i: The New England journal of medicine. - 1533-4406. ; 374:3, s. 223-232
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Tidskriftsartikel (refereegranskat)abstract
- Background Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown. Methods We sequenced the exomes of five members of a four-generation family, three of whom had infertility due to oocyte meiosis I arrest. We performed Sanger sequencing of a candidate gene, TUBB8, in DNA samples from these members, additional family members, and members of 23 other affected families. The expression of TUBB8 and all other β-tubulin isotypes was assessed in human oocytes, early embryos, sperm cells, and several somatic tissues by means of a quantitative reverse-transcriptase-polymerase-chain-reaction assay. We evaluated the effect of the TUBB8 mutations on the assembly of the heterodimer consisting of one α-tubulin polypeptide and one β-tubulin polypeptide (α/β-tubulin heterodimer) in vitro, on microtubule architecture in HeLa cells, on microtubule dynamics in yeast cells, and on spindle assembly in mouse and human oocytes. Results We identified seven mutations in the primate-specific gene TUBB8 that were responsible for oocyte meiosis I arrest in 7 of the 24 families. TUBB8 expression is unique to oocytes and the early embryo, in which this gene accounts for almost all the expressed β-tubulin. The mutations affect chaperone-dependent folding and assembly of the α/β-tubulin heterodimer, disrupt microtubule behavior on expression in cultured cells, alter microtubule dynamics in vivo, and cause catastrophic spindle-assembly defects and maturation arrest on expression in mouse and human oocytes. Conclusions TUBB8 mutations have dominant-negative effects that disrupt microtubule behavior and oocyte meiotic spindle assembly and maturation, causing female infertility. (Funded by the National Basic Research Program of China and others.).
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| 3. |
- Feng, Ruizhi, et al.
(författare)
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MiRNA-320 in the human follicular fluid is associated with embryo quality in vivo and affects mouse embryonic development in vitro.
- 2015
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Previous work from our laboratory demonstrated the existence of miRNAs in human follicular fluid. In the current study, we have sought to identify miRNAs that might affect oocyte/embryo quality in patients undergoing intracytoplasmic sperm injection and to investigate their roles in in vitro fertilization outcomes in mouse oocytes. 53 samples were classified as Group 1 (high quality) if the day-3 embryos had seven and more cells or as Group 2 (low quality) if the embryos had six and fewer cells. TaqMan Human microRNAs cards and qRT-PCR were performed to verify differently expressed miRNAs. The function of the corresponding miRNA was investigated in mouse oocytes by injecting them with miRNA-inhibitor oligonucleotides. We found that hsa-miR-320a and hsa-miR-197 had significantly higher expression levels in the Group 1 follicular fluids than in Group 2 (p = 0.0073 and p = 0.008, respectively). Knockdown of mmu-miR-320 in mouse oocytes strongly decreased the proportions of MII oocytes that developed into two-cell and blastocyst stage embryos (p = 0.0048 and p = 0.0069, respectively). Wnt signaling pathway components had abnormal expression level in miR-320 inhibitor-injected oocytes. This study provides the first evidence that miRNAs in human follicular fluid are indicative of and can influence embryo quality.
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| 4. |
- Song, Kai, et al.
(författare)
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Constant Current Charging and Maximum System Efficiency Tracking for Wireless Charging Systems Employing Dual-Side Control
- 2020
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Ingår i: IEEE Transactions on Industry Applications. - 0093-9994 .- 1939-9367. ; 56:1, s. 622-634
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Tidskriftsartikel (refereegranskat)abstract
- Wireless power transfer (WPT) systems have attracted much attention because of their safety, convenience, and environmental friendliness. For wireless supercapacitor charging, the system efficiency and charging current are highly dependent on the load that varies over a wide range. In this article, a simultaneous maximum system efficiency (MSE) tracking and constant current (CC) charging control scheme for a supercapacitor is proposed. For CC charging, a double-sided LCC topology is chosen due to its characteristic of providing a load-independent output current. Furthermore, the impact of the coil internal resistance on the system characteristics (especially the charging current) is investigated, so a semiactive rectifier is introduced on the secondary side to achieve accurate CC charging and improve the system robustness. Based on the variable-step perturbation and observation algorithm, the MSE is tracked by searching for the minimum system input dc current using a primary-side buck converter on the premise that the charging current reaches its target value. The abovementioned two control loops are independent, and mutual communication is unnecessary when they cooperate; thus, the system is simplified. The simulation and experimental results show great consistency with the theoretical analysis. The experimental system maintains the MSE of 86% during charging the supercapacitor from 20 to 50 V with 2 A.
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| 5. |
- Teng, Yiran, et al.
(författare)
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Deep-reinforcement-learning-based RMSCA for space division multiplexing networks with multi-core fibers [Invited Tutorial]
- 2024
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Ingår i: Journal of Optical Communications and Networking. - 1943-0620 .- 1943-0639. ; 16:7, s. C76-C87
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Tidskriftsartikel (refereegranskat)abstract
- The escalating demands for network capacities catalyze the adoption of space division multiplexing (SDM) technologies. With continuous advances in multi-core fiber (MCF) fabrication, MCF-based SDM networks are positioned as a viable and promising solution to achieve higher transmission capacities in multi-dimensional optical networks. However, with the extensive network resources offered by MCF-based SDM networks comes the challenge of traditional routing, modulation, spectrum, and core allocation (RMSCA) methods to achieve appropriate performance. This paper proposes an RMSCA approach based on deep reinforcement learning (DRL) for MCF-based elastic optical networks (MCF-EONs). Within the solution, a novel state representation with essential network information and a fragmentation-aware reward function were designed to direct the agent in learning effective RMSCA policies. Additionally, we adopted a proximal policy optimization algorithm featuring an action mask to enhance the sampling efficiency of the DRL agent and speed up the training process. The performance of the proposed algorithm was evaluated with two different network topologies with varying traffic loads and fibers with different numbers of cores. The results confirmed that the proposed algorithm outperforms the heuristics and the state-of-the-art DRL-based RMSCA algorithm in reducing the service blocking probability by around 83% and 51%, respectively. Moreover, the proposed algorithm can be applied to networks with and without core switching capability and has an inference complexity compatible with real-world deployment requirements.
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