Directly modulated parity-time symmetric single-mode Fabry-Perot laser.

Effective manipulation of resonant mode, output power and modulation bandwidth of lasers are all of vital importance for practical application scenarios such as communication systems. We show that by breaking the parity-time (PT) symmetry, single mode operation lasing can be realized in an intrinsic multiple mode Fabry-Perot (FP) resonator. Two identical FP resonators are employed to establish a symmetric system and high output power can be achieved with lower fabrication difficulty and intracavity losses compared with ring resonators. The small-signal response and direct modulation of the PT-symmetric FP laser have also been demonstrated with electrical pumping. Our work opens new avenues for mode selection of high-performance FP lasers and provides a cost-effective candidate for practical applications such as communication systems.

Hybrid-integrated wideband tunable optoelectronic oscillator.

As a photonic-based microwave signal generation method, the optoelectronic oscillator (OEO) has the potential of meeting the increasing demand of practical applications for high frequency, broadband tunability and ultra-low phase noise. However, conventional OEO systems implemented with discrete optoelectronic devices have a bulky size and low reliability, which extremely limits their practical applications. In this paper, a hybrid-integrated wideband tunable OEO with low phase noise is proposed and experimentally demonstrated. The proposed hybrid integrated OEO achieves a high integration level by first integrating a laser chip with a silicon photonic chip, and then connecting the silicon photonic chip with electronic chips through wire-bonding to microstrip lines. A compact fiber ring and an yttrium iron garnet filter are also adopted for high-Q factor and frequency tuning, respectively. The integrated OEO exhibits a low phase noise of -128.04 dBc/Hz @ 10 kHz for an oscillation frequency of 10 GHz. A wideband tuning range from 3 GHz to 18 GHz is also obtained, covering the entire C, X, and Ku bands. Our work demonstrates an effective way to achieve compact high-performance OEO based on hybrid integration, and has great potential in a wide range of applications such as modern radar, wireless communication, and electronic warfare systems.

Phase-diagram investigation of frustrated 1D and 2D Ising models in OEO-based Ising machine.

Ising machines have emerged as promising solvers for combinatorial optimization problems in recent years. In practice, these problems are often mapped into a frustrated Ising model due to randomness or competing interactions, which reduces the success ratio for finding the optimal solution. In this study, we simulate one-dimensional and two-dimensional frustrated Ising models in an Ising machine based on the optoelectronic oscillator. Our experiment aims to show the relationship between the Fourier mode of the coupling matrix and the spin distribution under frustration. The results prove the validity of the theoretical predictions and provide insights into the behavior of Ising machines in the presence of frustration. We believe it would help to develop a better strategy to improve the performance of Ising machines.

Simple method for microwave photonic temperature interrogation with high resolution and sensitivity.

We propose a microwave photonic temperature interrogation system with high resolution and sensitivity based on temperature-to-time mapping with a simple structure. In this work, a bidirectional chirped optical signal is constructed, and the temperature information is mapped to the time interval change of the output pulses by filtering the bidirectional chirped optical signal using the transmission spectrum of a Fabry-Perot filter. Only a low-speed oscilloscope is required to extract the time interval of the output pulses in the proposed scheme, and complex data processing as well as synchronizing processes are avoided. In a proof-of-concept experiment, a high temperature interrogation sensitivity of 18.24 µs/°C and a high resolution of 0.035°C are realized, demonstrating good potential for practical applications.

Bandwidth superposition of linearly chirped microwave waveforms based on a Fourier domain mode-locked optoelectronic oscillator.

Optoelectronic oscillators (OEOs) are promising for radar, communication and electronic countermeasure systems. Among them, frequency-scanning OEOs with wide instantaneous bandwidth are needed for many advanced applications. In this work, we demonstrate a novel system to generate bandwidth-doubled linearly chirped microwave waveforms (LCMWs) based on bandwidth superposition using a Fourier domain mode-locked OEO (FDML OEO). In the proposed system, bandwidth-doubling is achieved by re-modulating the generated LCMW of the FDML OEO onto a frequency-scanning optical carrier signal with the help of an external Mach-Zehnder modulator. LCMWs with wide frequency scanning instantaneous bandwidth of 10 GHz are experimentally obtained. Meanwhile, these LCMWs are tunable in an ultra-wide frequency range from 1 to 39 GHz. Moreover, they are with high frequency sweep linearity of 0.5%. Our work presents a simple method to generate tunable wide-band LCMWs for potential microwave sources.

Ultra-fast full-field optical characterization of CW lasers based on optical frequency comb, wavelength-to-time mapping and phase-diversity.

Optical frequency comb (OFC), a periodic optical pulse train in time domain, has been widely employed to measure optical frequency due to its equidistant modes in the frequency domain. Here, we propose and demonstrate a novel optical spectrum analyzer for CW lasers based on stretching the OFC in a dispersive element and mapping the frequency comb into the time domain. The optical spectrum analyzer also provides instantaneous full-field (wavelength, amplitude and phase) optical characterization capability by combining with optical phase-diversity technology. Experimental results show that we successfully trace the evolution of modulated lasers with a measurement speed of ∼51 MHz (related to the pulse repetition of the OFC) and a high spectral resolution of ∼21 pm. Thanks to the use of wavelength-to-time mapping and OFC, the single channel measurement range of the proposed system can reach ∼10 nm, which breaks the restriction of the bandwidth of photodetector.

Microwave photonic injection locking frequency divider based on a tunable optoelectronic oscillator.

We present a novel broadband divide-by-2 microwave photonic injection locking frequency divider (ILFD) based on a dual-loop optoelectronic oscillator (OEO). In the proposed scheme, a tunable microwave photonic filter is used to replace the traditional electrical filter, which makes sure a large tuning range of the ILFD. The microwave photonic ILFD whose center frequency tracks the tunable frequency of the free-running OEO, links up with every single locking range together. Thus the frequency range is only determined by the tunable OEO. In the experiment, a wide operating frequency range from 4.51 GHz to 34.88 GHz is realized. Furthermore, a divide-by-3 ILFD is experimentally demonstrated with the help of a frequency mixer.

Prognostic Significance of ACP5 in Human Gastric Cancer.

INTRODUCTION: Tartrate-resistant acid phosphatase (ACP5) plays crucial roles in multiple pathological processes, including the genesis and progression of malignant tumors. We performed this study with the purpose of determining whether ACP5 is a crucial biomarker significantly related to prognoses of gastric cancer (GC) patients. METHODS: The expression level of ACP5 level was assessed among 170 GC specimens using immunohistochemistry. The associations between ACP5 expression and clinicopathological variables were evaluated. Univariate and multivariate Cox regression analyses were performed to confirm independent prognostic factors for GC patients. RESULTS: It was revealed that ACP5 expression level in GC tissue was significantly associated with depth of invasion (p = 0.029) and TNM stage (p = 0.036). ACP5 was demonstrated by multivariate Cox regression analysis to be an independent prognostic factor for overall survival (OS) (p = 0.001) and recurrence-free survival (RFS) (p = 0.011) of GC patients. CONCLUSIONS: The expression of ACP5 in GC tissue was significantly higher than that in normal tissues, and its overexpression was associated with a poorer prognosis, suggesting its potential roles in preventing and treating GC.

Photonic-assisted radio frequency self-interference cancellation and frequency down-conversion based on polarization multiplexing modulation.

We report a photonic-assisted radio frequency self-interference cancellation (RF-SIC) and frequency down-conversion scheme based on a dual-polarization Mach-Zehnder modulator (DP-MZM) by using a polarization manipulation method. In the proposed scheme, the self-interference signal is directly canceled in the optical domain by simply controlling the polarization states between the output of the DP-MZM and the polarizer. Frequency down-conversion is achieved by optoelectronic frequency mixing. In the proof-of-concept experiment, the interference cancellation of the single-frequency signal and wideband signal was conducted. The proposed RF-SIC and frequency down-conversion system has flexible tunability, simple structure, and low cost, which can find potential applications in radio-over-fiber systems.

Photonic generation of multiband and multi-format microwave signals based on a single modulator.

We report a photonic scheme to generate multiband and multi-format microwave signals based on a commercial dual-polarization Mach-Zehnder modulator (DP-MZM). The key novelty of this work is the compact signal generator benefitting from the single modulator and the flexible multi-format signals at the multiband. The upper Mach-Zehnder modulator (MZM) of the DP-MZM is used to generate an optical frequency comb, while the lower MZM is driven by baseband electrical coding or single-chirp signal to obtain the multi-format modulated optical signal. The proposed scheme is theoretically analyzed and experimentally demonstrated. A multiband phase-coded microwave signal with a bit rate of 2 Gb/s and complementary linearly chirped microwave waveform pairs with a time duration of 1 µs and a bandwidth of 2 GHz have been successfully generated. The performance of pulse compression of generated signals is also demonstrated.

Dual-chirp Fourier domain mode-locked optoelectronic oscillator.

Optoelectronic oscillators (OEOs) have been widely investigated to generate ultra-pure single-frequency microwave signals. Here, we propose and experimentally demonstrate a dual-chirp Fourier domain mode-locked (FDML) OEO to generate dual-chip microwave waveforms. In the proposed FDML OEO, a frequency-scanning dual-passband microwave photonics filter based on phase-modulation-to-intensity-modulation conversion using an optical notch filter and two laser diodes is incorporated into the OEO cavity. Fourier domain mode-locking operation is achieved by synchronizing the scanning period of the filter to the cavity round-trip time. Tunable dual-chirp microwave waveforms with a large time-bandwidth product are generated directly from the FDML OEO cavity in the experiment, which can be used in modern radar systems to improve its range-Doppler resolution.

Multiple-frequency measurement based on a Fourier domain mode-locked optoelectronic oscillator operating around oscillation threshold.

We propose and experimentally demonstrate a photonic-assisted approach to microwave frequency measurement based on frequency-to-time mapping using a Fourier domain mode-locked optoelectronic oscillator (FDML OEO) operating around oscillation threshold. A relationship between the frequency of the unknown input microwave signals and the time difference of the output pulses is established with the help of the frequency scanning capability of the FDML OEO and, thus, can be used for microwave frequency measurement. The proposed scheme is characterized as having broad bandwidth, high resolution, multiple-frequency detection capability, and tunable measurement range. Microwave frequency measurement with a measurement range up to 16 GHz and a low measurement error of 0.07 GHz is realized.

Microwave photonics frequency-to-time mapping based on a Fourier domain mode locked optoelectronic oscillator.

An approach to microwave photonics frequency-to-time mapping (MWP FTM) is proposed based on a Fourier domain mode locked optoelectronic oscillator (FDML OEO). In this approach, a relationship between the frequency of the input microwave signal and the time difference of the output pulses is established with the help of the fast frequency scanning capability of the FDML OEO. The ability to measure the microwave spectral information in the time domain using the proposed system has the potential to enable new metrology and signal processing schemes with a superior performance in terms of real-time bandwidth and operation speed compare with traditional approaches. As an application example, single and multi-tone microwave frequency measurement are experimentally demonstrated based on the proposed MWP FTM system.

Integrated optoelectronic oscillator.

With the rapid development of the modern communication systems, radar and wireless services, microwave signal with high-frequency, high-spectral-purity and frequency tunability as well as microwave generator with light weight, compact size, power-efficient and low cost are increasingly demanded. Integrated microwave photonics (IMWP) is regarded as a prospective way to meet these demands by hybridizing the microwave circuits and the photonics circuits on chip. In this article, we propose and experimentally demonstrate an integrated optoelectronic oscillator (IOEO). All of the devices needed in the optoelectronic oscillation loop circuit are monolithically integrated on chip within size of 5×6cm2. By tuning the injection current to 44 mA, the output frequency of the proposed IOEO is located at 7.30 GHz with phase noise value of -91 dBc/Hz@1MHz. When the injection current is increased to 65 mA, the output frequency can be changed to 8.87 GHz with phase noise value of -92 dBc/Hz@1MHz. Both of the oscillation frequency can be slightly tuned within 20 MHz around the center oscillation frequency by tuning the injection current. The method about improving the performance of IOEO is carefully discussed at the end of in this article.

Interaction between RAD51 and MCM Complex Is Essential for RAD51 Foci Forming in Colon Cancer HCT116 Cells.

Colon cancer remains one of the most common digestive system malignancies in the World. This study investigated the possible interaction between RAD51 and minichromosome maintenance proteins (MCMs) in HCT116 cells, which can serve as a model system for forming colon cancer foci. The interaction between RAD51 and MCMs was detected by mass spectrometry. Silenced MCM vectors were transfected into HTC116 cells. The expressions of RAD51 and MCMs were detected using Western blotting. Foci forming and chromatin fraction of RAD51 in HCT116 cells were also analyzed. The results showed that RAD51 directly interacted with MCM2, MCM3, MCM5, and MCM6 in colon cancer HTC116 cells. Suppression of MCM2 or MCM6 by shRNA decreased the chromatin localization of RAD51 in HTC116 cells. Moreover, silenced MCM2 or MCM6 decreased the foci forming of RAD51 in HTC116 cells. Our study suggests that the interaction between MCMs and RAD51 is essential for the chromatin localization and foci forming of RAD51 in HCT116 cell DNA damage recovery, and it may be a theoretical basis for analysis of RAD51 in tumor samples of colon cancer patients.

Long Non-Coding RNA HOXA Transcript at the Distal Tip as a Putative Biomarker of Metastasis and Prognosis: a Meta-Analysis.

BACKGROUND: Many studies demonstrated that the expression level of HOTTIP in cancerous tissues was significantly higher than that in adjacent normal tissues. Increased expression of HOTTIP was associated with metastasis and a poor prognosis. METHODS: The current meta-analysis collected all relevant articles and explored the association of HOTTIP expression levels with lymph node metastasis (LNM), distant metastasis (DM), and overall survival (OS) in multiple cancers. Literature collections were conducted by searching a number of electronic databases (up to December 31, 2015). The Meta-analysis was conducted using RevMan5.3 software and Stata SE12.0. RESULTS: A total of 602 patients with cancer from seven studies were included. The Meta-analysis results showed that lymph node metastasis occurred more frequently in patients with high HOTTIP expression than in patients with low HOTTIP expression (OR = 2.22, 95% CI: 1.47 - 3.37, p = 0.0002, fixed-effects model), and a similar result was observed between HOTTIP expression and distant metastasis (OR = 3.30 (95% CI: 1.78 - 6.12, p = 0.0001, fixed-effects model). Moreover, we found that cancer patients with high HOTTIP expression had a poorer overall survival than those with low HOTTIP expression (HR = 2.23, 95% CI: 1.64 - 2.83, p = 0.000, fixed-effects model). CONCLUSIONS: HOTTIP may serve as an independent biomarker for predicting the clinical outcome of cancer patients.

MEX3A promotes colorectal cancer migration, invasion and EMT via regulating the Wnt/ß-catenin signaling pathway.

BACKGROUND: Mex-3 RNA binding family members are well-established to be important in cancer development and progression. However, the functions of Mex-3 RNA binding family member A (MEX3A) in colorectal cancer (CRC) metastasis remain poorly understood. In this study, we aim to reveal the function and the mechanism of MEX3A in promoting CRC metastasis. METHODS: We used multiple databases including TCGA database, UALCAN, LinkedOmics, CancerSEA, GeneMANIA and STRING database to investigate the expression, the functions and underlying molecular mechanism of MEX3A in CRC. Multiple experimental methods were adapted to determine the study, including real-time PCR (qPCR), immunohistochemistry (IHC), western blot (WB), transfection, transwell migration and invasion assays, immunofluorescence (IF). RESULTS: We found that MEX3A was significantly upregulated and correlated to tumor stage and lymph nodal metastasis in CRC through bioinformatics analysis and tissue immunohistochemistry (IHC). The higher expression of MEX3A in CRC correlated with poor recurrence-free survival (RFS) and overall survival (OS). In vitro studies showed that knockdown of MEX3A suppressed EMT transition, invasion and metastasis of CRC cells. Mechanistically, we revealed that MEX3A promotes epithelial-mesenchymal transition (EMT), invasion and metastasis of CRC cells by upregulating the Wnt/ß-catenin signaling pathway. CONCLUSION: In conclusion, our study reveals that MEX3A promotes CRC migration, invasion and EMT via regulating the Wnt/ß-catenin signaling pathway and could be a novel therapeutic target for this patient population.

Pumilio1 regulates NPM3/NPM1 axis to promote PD-L1-mediated immune escape in gastric cancer.

Abnormal regulation of RNA binding proteins (RBPs) plays an essential role in tumorigenesis and progression, but their functions and mechanisms remain largely elusive. Previously, we reported that Pumilio 1 (PUM1), a RBP, could regulate glycolysis metabolism and promote the progression of gastric cancer (GC). However, the role of PUM1 in tumor immune regulation remains largely elusive. In this study, we report that PUM1 induces immune escape through posttranscriptional regulation of PD-L1 in GC. We used multiplexed immunohistochemistry to analyze the correlation between PUM1 expression and immune microenvironment in GC. The effect of PUM1 deficiency on tumor killing of T cells was examined in vitro and in vivo. The molecular mechanism of PUM1 was evaluated via RNA immunoprecipitation, chromatin immunoprecipitation, Western blot, co-immunoprecipitation, and RNA stability assays. Clinically, elevated PUM1 expression is associated with high-expression of PD-L1, lack of CD8+ T cell infiltration and poor prognosis in GC patients. PUM1 positively regulates PD-L1 expression and PUM1 reduction enhances T cell killing of tumors. Mechanistically, PUM1 directly binds to nucleophosmin/nucleoplasmin 3 (NPM3) mRNA and stabilizes NPM3. NPM3 interacts with NPM1 to promote NPM1 translocation into the nucleus and increase the transcription of PD-L1. PUM1 inhibits the anti-tumor activity of T cells through the PUM1/NPM3/PD-L1 axis. In summary, this study reveals the critical post-transcriptional effect of PUM1 in the modulation of PD-L1-dependent GC immune escape, thus provides a novel indicator and potential therapeutic target for cancer immunotherapy.

The predictive effect of immune therapy and chemotherapy under T cell-related gene prognostic index for Gastric cancer.

Background: Gastric cancer (GC) is one of the most common malignancies in the human digestive tract. CD4+T cells can eliminate tumor cells directly through the mechanism of cytolysis, they can also indirectly attack tumor cells by regulating the tumor TME. A prognostic model of CD4+T cells is urgently needed to improve treatment strategies and explore the specifics of this interaction between CD4+T cells and gastric cancer cells. Methods: The detailed data of GC samples were downloaded from the Cancer Genome Atlas (TCGA), GSE66229, and GSE84437 datasets. CD4+ T cell-related genes were identified to construct a risk-score model by using the Cox regression method and validated with the Gene Expression Omnibus (GEO) dataset. In addition, postoperative pathological tissues of 139 gastric cancer patients were randomly selected for immunohistochemical staining, and their prognostic information were collected for external verification. Immune and molecular characteristics of these samples and their predictive efficacy in immunotherapy and chemotherapy were analysed. Results: The training set and validation set had consistent results, with GC patients of high PROC and SERPINE1 expression having poorer prognosis. In order to improve their clinical application value, we constructed a risk scoring model and established a high-precision nomogram. Low-risk patients had a better overall survival (OS) than high-risk patients, consistent with the results from the GEO cohort. Furthermore, the risk-score model can predict infiltration of immune cells in the tumor microenvironment of GC, as well as the response of immunotherapy. Correlations between the abundance of immune cells with PROC and SERPINE1 genes were shown in the prognostic model according to the training cohort. Finally, sensitive drugs were identified for patients in different risk subgroup. Conclusion: The risk model not only provides a basis for better prognosis in GC patients, but also is a potential prognostic indicator to distinguish the molecular and immune characteristics of the tumor, and its response to immune checkpoint inhibitor (ICI) therapy and chemotherapy.

Large-scale coherent Ising machine based on optoelectronic parametric oscillator.

Ising machines based on analog systems have the potential to accelerate the solution of ubiquitous combinatorial optimization problems. Although some artificial spins to support large-scale Ising machines have been reported, e.g., superconducting qubits in quantum annealers and short optical pulses in coherent Ising machines, the spin stability is fragile due to the ultra-low equivalent temperature or optical phase sensitivity. In this paper, we propose to use short microwave pulses generated from an optoelectronic parametric oscillator as the spins to implement a large-scale Ising machine with high stability. The proposed machine supports 25,600 spins and can operate continuously and stably for hours. Moreover, the proposed Ising machine is highly compatible with high-speed electronic devices for programmability, paving a low-cost, accurate, and easy-to-implement way toward solving real-world optimization problems.