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1.
Toxicology ; 435: 152422, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32112805

RESUMO

Ribavirin has been proven to be an antiviral treatment, whereas there are still risks of hemolysis and congenital malformation. Abnormal cardiac development contributes to the occurrence and development of many heart diseases. However, there is so far no evidence that ribavirin induces human cardiac developmental toxicity. Herein, we employed the cardiac differentiation model of human induced pluripotent stem cells (hiPSCs) to determine the impact of ribavirin on heart development. Our data showed that ribavirin at clinically high concentrations (5 and 10 µM) significantly inhibited the proliferation and differentiation of hiPSCs from mesoderm to cardiac progenitor cells and cardiac progenitor cells to cardiomyocytes, but not from pluripotent status to mesoderm. Meanwhile, DCFH-DA staining revealed that ribavirin could increase ROS content in the mid-phase of differentiation. In addition, ribavirin treatment (1, 5 and 10 µM) remarkably caused DNA damage which was shown by the increase of γH2AX-positive cells and upregulation of the p53 during the differentiation of hiPSCs from mesoderm to cardiac progenitor cells. Moreover, exposuring to ribavirin (5 and 10 µM) markedly upregulated the expression of lncRNAs Gas5 in both mid-phase and late phase of differentiation and HBL1 in the mid-phase. In conclusion, our results suggest that ribavirin is detrimental in cardiac differentiation of hiPSCs, which may be associated with DNA damage, upregulated p53 and increased Gas5. It may provide the evidence for the rational clinical application of ribavirin.

2.
FEBS Open Bio ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053740

RESUMO

Iron overload affects the cell cycle of various cell types, but the effect of iron overload on human pluripotent stem cells (hPSCs) has not yet been reported. Here, we show that the proliferation capacities of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) were significantly inhibited by ferric ammonium citrate (FAC) in a concentration-dependent manner. Additionally, deferoxamine (DFO) protected hESCs/hiPSCs against FAC-induced cell cycle arrest. However, iron overload did not affect pluripotency in hESCs/hiPSCs. Further, treatment of hiPSCs with FAC resulted in excess reactive oxygen species production and DNA damage. Collectively, our findings provide new insights into the role of iron homeostasis in the maintenance of self-renewal in hPSCs.

3.
J Cell Physiol ; 235(3): 2753-2760, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31541452

RESUMO

Cardiomyocytes differentiated from human-induced pluripotent stem cells (hiPSCs) hold great potential for therapy of heart diseases. However, the underlying mechanisms of its cardiac differentiation have not been fully elucidated. Hippo-YAP signal pathway plays important roles in cell differentiation, tissue homeostasis, and organ size. Here, we identify the role of Hippo-YAP signal pathway in determining cardiac differentiation fate of hiPSCs. We found that cardiac differentiation of hiPSCs were significantly inhibited after treatment with verteporfin (a selective and potent YAP inhibitor). During hiPSCs differentiation from mesoderm cells (MESs) into cardiomyocytes, verteporfin treatment caused the cells retained in the earlier cardiovascular progenitor cells (CVPCs) stage. Interestingly, during hiPSCs differentiation from CVPC into cardiomyocytes, verteporfin treatment induced cells dedifferentiation into the earlier CVPC stage. Mechanistically, we found that YAP interacted with transcriptional enhanced associate domain transcription factor 3 (TEAD3) to regulate cardiac differentiation of hiPSCs during the CVPC stage. Consistently, RNAi-based silencing of TEAD3 mimicked the phenotype as the cells treated with verteporfin. Collectively, our study suggests that YAP-TEAD3 signaling is important for cardiomyocyte differentiation of hiPSCs. Our findings provide new insight into the function of Hippo-YAP signal in cardiovascular lineage commitment.

4.
Opt Lett ; 44(18): 4503-4506, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31517917

RESUMO

A chromatic dispersion (CD) immune microwave photonic phase shifter (MPPS) based on double-sideband (DSB) modulation is proposed and demonstrated. An optical spectrum processor introduces the phase shift to the MPPS. The DSB signals along two orthogonal polarizations are demodulated to two RF signals with both quadrature amplitude and phase items, transferring the CD-induced power fading to the phase item of the synthetic RF signals. Experimental results show that the RF signals over 14-25 GHz obtain random phase shift in 360° range without a power fading point (PFP) after passing through a dispersion compensation fiber with CD of -331 ps/nm. The phase variation and power variation of the phase-shifted signal are <±5.7° and <±0.9 dB, respectively, at the original PFP at 16 GHz.

5.
Opt Express ; 27(14): 20064-20072, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31503756

RESUMO

In this paper, we propose an all-optical system for the generation of binary phase-coded microwave pulses without baseband components. The scheme is based on a dual-parallel Mach-Zehnder modulator (DPMZM). By properly applying the coding signals and the microwave signals to the precisely biased DPMZM, accurate π phase shift binary phase-coded microwave pulses without baseband components can be generated. The proposed system has an extremely simple and stable all-optical structure, leading to a large frequency tuning range and a high signal quality. The operation of the system is very easy. The generation of the 2-Gbit/s 14-GHz and 4-Gbit/s 16-GHz binary phase-coded microwave pulses under different coding signal amplitudes and microwave carrier powers are experimental verified. The results show that the proposed binary phase-coded microwave pulses generation system has high quality and performance.

6.
Opt Express ; 27(15): 20774-20784, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31510166

RESUMO

A photonic microwave phase-coded pulse generator is proposed and experimentally demonstrated based on the principle of vector sum. The key component of the proposed pulse generator is an integrated polarization-division multiplexing Mach-Zehnder modulator (PDM-MZM) and a 90° hybrid coupler. By properly setting the data sequences applied to the specially biased PDM-MZM, binary and quaternary phase-coded microwave pulses (PCMPs) that are free from the background signals can be generated. Since no filters and polarization adjustment are involved, the proposed pulse generator is characterized by a simple structure, low-loss, flexible frequency tunability and high long-term stability. The experimental results show that background-free 4 Gb/s Barker and Frank PCMPs at 18 GHz and 2 Gb/s Barker and Frank PCMPs at 24 GHz are successfully generated. The calculated pulse compression ratio and peak-to-side lobe ratio are in good agreement with the theoretical values.

7.
Opt Lett ; 44(12): 3138-3141, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31199400

RESUMO

A photonic microwave frequency shift keying (FSK) signal generator is proposed and experimentally demonstrated based on an equivalent photonic switch (EPS). The EPS is constructed using a polarization-multiplexing dual-drive Mach-Zehnder modulator (PM-DMZM). By properly controlling the data sequences and RF signals applied to the PM-DMZM, microwave FSK signals with flexible frequency intervals can be obtained. The proposed FSK signal generator features the advantages of a simple structure, low loss, good stability, and great frequency tunability. In addition, the proposed setup can also be easily reconfigured to generate microwave amplitude shift keying and phase shift keying signals. The experimental results show that 2 Gb/s at 5/14 GHz and 1 Gb/s at 6/20 GHz microwave FSK signals are successfully generated, after transmission over 5 km single-mode fiber. The required received optical power at 7% forward error correction threshold is only -14.48 dBm.

8.
Opt Lett ; 44(8): 2121-2124, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30985826

RESUMO

Distributed coherent aperture radar (DCAR) is an important direction for next-generation radar due to its high sensitivity. The challenge to realize DCAR is the synchronization among geographically distributed radar units. We propose an optical network for DCAR synchronization. The proposed network achieves functions of phase-coded pulse generation, time synchronization, and phase synchronization with the help of microwave photonics techniques. Proof-of-concept experiments are conducted in fiber and space transmission scenarios. The combined radar beams have negligible energy loss when synchronization is achieved.

9.
Opt Lett ; 44(2): 255-258, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30644874

RESUMO

An optically controlled system for generating and continuously steering radio frequency (RF) signals with double orbital angular momentum (OAM) modes is proposed and experimentally demonstrated. The optical carrier's utilization efficiency can be doubled through the distinct electro-optical modulation, which is based on two single-sideband modulation operations on a single optical carrier through a customized dual-parallel Mach-Zehnder modulator. A constructive antenna phase feeding method of a circular antenna array for collectively forming and steering an OAM radio beam is proposed and illustrated. A proof-of-concept experiment is conducted to generate and steer a dual-mode RF-OAM beam to two different two-dimensional (2D) directions, independently and simultaneously. One 17 GHz OAM beam with mode L=1 is continuously steered to 2D directions (:, 0°, 0°), (:, 0°, 1.70°), (:, 0°, 3.87°), (:, 0°, 6.17°), and(:, 0°, 7.80°), with vortex properties, where ":" means "any value of." Meanwhile, the 19 GHz OAM beam with mode L=-1 carried is steered from (:, 0°, 0°) to (:, 0°, -6.72°), and the constellations are obtained successfully.

10.
Opt Lett ; 44(1): 155-158, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30645573

RESUMO

A Hilbert-transform-based broadband chromatic dispersion (CD) compensation scheme for radio-over-fiber links is proposed and experimentally demonstrated. By constructing a Hilbert transform path, CD-induced phase shifts, which initially lead to periodic power fading of the output RF signals, are transferred to the phases of the RF signals. As a result, the powers of the output RF signals are free from the effect of CD in a broadband frequency range. Experimental results show that a flat normalized amplitude-frequency response is actualized within 2-24 GHz, with only 3.02 dB/4.27 dB power fluctuation after transmission over an equivalent of a 38.6 km/43.6 km single-mode fiber. Besides, compared with a conventional dispersive path, the proposed CD compensation scheme significantly improves the third-order spurious-free dynamic range by 23.60 dB.

11.
Opt Express ; 26(1): 454-462, 2018 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-29328322

RESUMO

An optically-controlled phase-tunable microwave mixer based on a dual-drive dual-parallel Mach-Zehnder modulator (DDDP-MZM) is proposed, which supports wideband phase shift and immunity to power fading caused by chromatic dispersion. By using carrier-suppressed single side-band (CS-SSB) modulation for the local oscillator (LO) signal and carrier-suppressed double side-band (CS-DSB) modulation for the input signal, no vector superposition for the same output microwave frequency occurs, making the system immune from power fading caused by chromatic dispersion. Phase tuning is achieved by shifting the phase of the LO signal, and direct electrical tuning of the wideband microwave input signal is avoided, thus supporting large working bandwidth. A phase-shifted down-conversion experiment is carried out, where a phase shift with 0 ~390° and down-conversion are achieved with a phase variation of less than 5° and power variation less than 3.5 dBm when the input signal sweeps between 12 ~16 GHz. The mixer is simple and power-efficient since it uses a single compact modulator, and does not require any optical filters. No power notches are observed in the output microwave spectrum, proving that the dispersion-related frequency-selective fading is mitigated.

12.
Opt Lett ; 41(11): 2549-52, 2016 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-27244411

RESUMO

An indirect approach based on phase measurement is proposed to measure the rotational Doppler frequency shift, which takes full advantage of the phase structure of orbital angular momentum (OAM) beams in radio domain, using a vector network analyzer (VNA) as a phase discriminator. A proof-of-concept experiment is established by an optical-controlled system with the OAM state of 1. By analyzing the experiment's results, the rotational Doppler frequency shift is measured as 24.83 Hz (max error rate 0.67%) at 50π rad/s rotational velocity, deducing the rotational velocity as 50.18π (average error rate 0.36%).

13.
Opt Lett ; 39(9): 2652-5, 2014 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-24784069

RESUMO

A system for generating radio frequency signals with orbital angular momentum (OAM) is proposed and certificated for the first time, which employs an array of multiple optical-true-time-delay elements and circular antennas array (CAAs). A constructive Fourier series theory about CAAs collectively forming an OAM radio beam is demonstrated. An optical spectrum processor offers the four lines high-resolution time delay by adding a series of linear optical phase shifts. The OAM radio beam with topological charge L=1 is produced and measured successfully.

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