Near-ultraviolet photon-counting dual-comb spectroscopy.

Ultraviolet spectroscopy provides unique insights into the structure of matter with applications ranging from fundamental tests to photochemistry in the Earth's atmosphere and astronomical observations from space telescopes1-8. At longer wavelengths, dual-comb spectroscopy, using two interfering laser frequency combs, has become a powerful technique capable of simultaneously providing a broad spectral range and very high resolution9. Here we demonstrate a photon-counting approach that can extend the unique advantages of this method into ultraviolet regions where nonlinear frequency conversion tends to be very inefficient. Our spectrometer, based on two frequency combs with slightly different repetition frequencies, provides a wide-span, high-resolution frequency calibration within the accuracy of an atomic clock, and overall consistency of the spectra. We demonstrate a signal-to-noise ratio at the quantum limit and an optimal use of the measurement time, provided by the multiplexed recording of all spectral data on a single photon-counter10. Our initial experiments are performed in the near-ultraviolet and in the visible spectral ranges with alkali-atom vapour, with a power per comb line as low as a femtowatt. This crucial step towards precision broadband spectroscopy at short wavelengths paves the way for extreme-ultraviolet dual-comb spectroscopy, and, more generally, opens up a new realm of applications for photon-level diagnostics, as encountered, for example, when driving single atoms or molecules.

Optical frequency domain reflectometry with broadened frequency sweep range assisted by a dual electro-optic frequency comb.

We propose an optical frequency domain reflectometry (OFDR) with the assistance of a dual electro-optic frequency comb (EOFC), which is intended to improve the system spatial resolution. As the spatial resolution of an OFDR system is inversely proportional to the frequency sweep range, the EOFC acts as a multi-frequency light source for collecting Rayleigh backscattering signals, which are combined to extend the effective frequency sweep range. By utilizing this technique, we have successfully expanded the experimental frequency sweep range to hundreds of gigahertz, achieving a sub-millimeter spatial resolution.

Dexamethasone Liposomes Alleviate Osteoarthritis in miR-204/-211-Deficient Mice by Repolarizing Synovial Macrophages to M2 Phenotypes.

We undertook this study to investigate the effects and mechanisms of dexamethasone liposome (Dex-Lips) on alleviating destabilization of the medial meniscus (DMM)-induced osteoarthritis (OA) in miR-204/-211-deficient mice. Dex-Lips was prepared by the thin-film hydration method. The characterization of Dex-Lips was identified by the mean size, zeta potential, drug loading, and encapsulation efficiencies. Experimental OA was established by DMM surgery in miR-204/-211-deficient mice, and then Dex-Lips was treated once a week for 3 months. Von Frey filaments was used to perform the pain test. The inflammation level was evaluated with quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Polarization of macrophages was evaluated by immunofluorescent staining. X-ray, micro-CT scanning, and histological observations were conducted in vivo on DMM mice to describe the OA phenotype. We found that miR-204/-211-deficient mice displayed more severe OA symptoms than WT mice after DMM surgery. Dex-Lips ameliorated DMM-induced OA phenotype and suppressed pain and inflammatory cytokine expressions. Dex-Lips could attenuate pain by regulating PGE2. Dex-Lips treatments reduced the expression of TNF-α, IL-1ß, and IL-6 in DRG. Moreover, Dex-Lips could reduce inflammation in the cartilage and serum. Additionally, Dex-Lips repolarize synovial macrophages to M2 phenotypes in miR-204/-211-deficient mice. In conclusion, Dex-Lips inhibited the inflammatory response and alleviated the pain symptoms of OA by affecting the polarization of macrophages.

High-speed performance evaluation of ultra-flexible polymer waveguides supporting meter-scale optical interconnects.

We demonstrate bandwidth measurement and high-speed data transmission of meter-scale connectorized ultra-flexible multimode waveguide links with a maximum length of 180 cm. The pulses propagating through the waveguides broadened linearly with the increase of the length from 20 cm to 240 cm and the estimated mode delay from the pulse broadening was 0.093 ps/cm. The corresponding waveguide bandwidth decreased inversely with the increase of waveguide length, leading to a bandwidth-length product of 42 GHz·m. Degradation in bandwidth due to the introduction of bending or twisting was small when the samples were bent with a bending radius as small as 1 mm for 3 turns or twisted for 4 full turns, respectively. Error-free transmission of 30 Gb/s non-return-to-zero (NRZ) signal was achieved with a record link length up to 140 cm to the best of our knowledge. Our results show that the demonstrated flexible waveguides have both excellent optical and mechanical properties and are ideal for high-speed optical interconnects application especially those have a strict requirement on flexibility.

Single-exposure multi-wavelength diffraction imaging with blazed grating.

Multi-wavelength diffraction imaging is a lensless, high-resolution imaging technology. To avoid multiple exposures and enable high-speed data collection, here an innovative setup for the single-exposure multi-wavelength diffraction imaging based on a blazed grating is proposed. Since the blazed angle varies with the wavelength, the diffraction patterns for the individual wavelengths can be separated from each other and recorded in a single measurement at one time. A method of high-precision position alignment between different wavelength patterns is proposed in our system to achieve good image quality and high resolution. Experiments on a phase-only USAF resolution target and biological samples were carried out to verify the effectiveness of our proposed method. This proposed setup has such advantages as a simpler structure, fast recording, and algorithm robustness.

Early assessment of acute ischemic stroke in rabbits based on multi-parameter near-field coupling sensing.

BACKGROUND: Early diagnosis and continuous monitoring are the key to emergency treatment and intensive care of patients with acute ischemic stroke (AIS). Nevertheless, there has not been a fully accepted method targeting continuous assessment of AIS in clinical. METHODS: Near-field coupling (NFC) sensing can obtain the conductivity related to the volume of intracranial components with advantages of non-invasiveness, strong penetrability and real-time monitoring. In this work, we built a multi-parameter monitoring system that is able to measure changes of phase and amplitude in the process of electromagnetic wave (EW) reflection and transmission. For investigating its feasibility in AIS detection, 16 rabbits were chosen to establish AIS models by bilateral common carotid artery ligation and then were enrolled for monitoring experiments. RESULTS: During the 6 h after AIS, the reflection amplitude (RA) shows a decline trend with a range of 0.69 dB and reflection phase (RP) has an increased variation of 6.48° . Meanwhile, transmission amplitude (TA) and transmission phase (TP) decrease 2.14 dB and 24.29° , respectively. The statistical analysis illustrates that before ligation, 3 h after ligation and 6 h after ligation can be effectively distinguished by the four parameters individually. When all those parameters are regarded as recognition features in back propagation (BP) network, the classification accuracy of the three different periods reaches almost 100%. CONCLUSION: These results prove the feasibility of multi-parameter NFC sensing to assess AIS, which is promised to become an outstanding point-of-care testing method in the future.

High-resolution multi-wavelength lensless diffraction imaging with adaptive dispersion correction.

Multi-wavelength imaging diffraction system is a promising phase imaging technology due to its advantages of no mechanical movement and low complexity. In a multi-wavelength focused system, spectral bandwidth and dispersion correction are critical for high resolution reconstruction. Here, an optical setup for the multi-wavelength lensless diffraction imaging system with adaptive dispersion correction is proposed. Three beams with different wavelengths are adopted to illuminate the test object, and then the diffraction patterns are recorded by a image sensor. The chromatic correction is successfully realized by a robust refocusing technique. High-resolution images can be finally retrieved through phase retrieval algorithm. The effectiveness and reliability of our method is demonstrated in numerical simulation and experiments. The proposed method has the potential to be an alternative technology for quantitative biological imaging.

Wideband and high-resolution spectroscopy based on an ultra-fine electro-optic frequency comb with seed lightwave selection via injection locking.

The digital ultra-fine electro-optic frequency comb (UFEOFC) enables high-resolution spectroscopy in various applications with a limited bandwidth. In this Letter, we propose a novel, to the best of our knowledge, UFEOFC-based dual-comb spectroscopy to realize megahertz resolution and broadened bandwidth. An UFEOFC with 1 MHz line-spacing and 18 GHz bandwidth is generated and resolved in a dual-comb interferometer working in quasi-integer-ratio mode. One line selected from a master EOFC with 18 GHz line-spacing via optical injection locking serves as the seed lightwave. Successive selection of 20 lines realizes wideband measurement covering 360 GHz, and a reflectance spectrum of a phase-shift fiber Bragg grating is obtained in the demonstration. A spectrum with 360,000 lines is demodulated in 26 ms due to the low injection lock dead time set to be 300µs between adjacent lines, by which the figure of merit reaches 3.39×107. The system promotes more prospects in practical spectroscopic and sensing applications.

Microwave frequency measurement with high accuracy and wide bandwidth based on whispering-gallery mode barcode.

We propose and experimentally demonstrate a novel method for photonic-assisted microwave frequency measurement based on whispering-gallery mode (WGM) barcode, which is a dense spectrum generated by a micro-resonator that supports a large number of optical modes. The measurement relies on the relation between the microwave frequency and its unique barcode. The proposed system has the advantages of wide bandwidth, high accuracy, and multiple-frequency measurement capability. Microwave frequency measurement from 1 to 20 GHz is experimentally demonstrated with a measurement error of 40 kHz. For multi-tone signals, the frequency resolution is demonstrated to be less than 20 MHz. A dynamic multi-tone microwave signal consists of a 16-20 GHz linear frequency-modulated (LFM) signal, and a 10 GHz signal is measured to show the capability of multiple-frequency measurement. The system stability is also evaluated, and a self-reference method is proposed to maintain a long-term high-accuracy measurement.

Real-time channel conditional distribution tracking for intelligent decoding of optical IMDD signals.

In this Letter, we propose a real-time machine learning scheme of a tracking optical intensity-modulation and direct-detection (IMDD) system's conditional distribution using linear optical sampling and inline Gaussian mixer modeling (GMM) programming. End-to-end conditional distribution tracking enables an adaptive decoding of optical IMDD signals, with robustness to the bias point shift of the optical intensity modulator. Experimental demonstration is conducted over a 20-Gbits/s optical pulse amplitude modulation-4 (PAM-4) modulation system. Optical PAM-4 signals are optically down-sampled by short pulses to 250 Msa/s. Then, statistical characters of signal distribution can be estimated using inline GMM processing. Due to the real-time learned distribution, intelligent decoding of received signals exhibits a perfect adaptation to the changing bias point of a Mach-Zendner intensity modulator, enhancing the communication reliability with bit error rate (BER) below 3.8⋅10-3. In addition, the proposed scheme also provides the possibility of practical implementation to other machine learning signal decoding methods.

Rayleigh speckle-based wavemeter with high dynamic range and fast reference speckle establishment process assisted by optical frequency combs.

Compact speckle-based spectrometers that acquire lightwave wavelength from the speckle generated by turbid media are promising for high-resolution spectral analysis. For these devices, the reference establishment process is time consuming, and it is very difficult to obtain reference speckles covering a wide bandwidth with high resolution, which restricts the dynamic range in frequency (the ratio of bandwidth to resolution). In this Letter, we introduce optical frequency combs (OFCs) to the system to overcome these problems, which exist in the wavemeter based on Rayleigh speckle obtained from a single-mode fiber. In the experiment, the proposed wavemeter has a 1.5 nm bandwidth with 60 am resolution, covering a dynamic range in the frequency of 2×107, and a fast reference speckle establishment process that takes only 0.9 ms. The proposed method assisted by OFCs is a good prospect for a more practical speckle-based wavemeter with higher dynamic ranges.

Direct bandwidth measurement of multimode waveguides based on an optical sampling technique.

We demonstrate direct bandwidth measurement of 11-cm-long multimode polymer waveguides based on an optical sampling technique for the first time, to our knowledge. The pulse shape can be recovered after transmission due to the advantages such as high bandwidth and high refresh rate of optical sampling technology. A reduction in averaged bandwidth (bandwidth-length product) from 241 GHz (27 GHz·m) to 180 GHz (20 GHz·m) of straight waveguides is observed when using mode scramblers to fully stimulate the higher-order modes. The effects such as bending and crossing structure of the waveguides on the bandwidth are also investigated. The proposed method is effective for measuring the bandwidth and dispersion of meter- and centimeter-long waveguides, fibers, and optical devices.

Inflammation suppression by dexamethasone via inhibition of CD147-mediated NF-κB pathway in collagen-induced arthritis rats.

Dexamethasone (Dex) exhibits broad-spectrum anti-inflammatory effects in chronic destructive rheumatoid arthritis. We present in vivo and in vitro evidence supporting the preventive effects and underlying mechanisms of Dex on collagen-induced arthritis (CIA)-induced synovial injuries. After successful induction of CIA, Wistar rats were administered Dex intraperitoneally (1 mg/kg) three times a week for more than 2 weeks. In vivo, paw swelling, arthritis scores, and histological evaluations were analyzed to determine the therapeutic effects of Dex on the progression of arthritis. In vitro, CIA fibroblast-like synoviocytes (FLSs) were treated for 48 h with vehicle (control group), 10 ng/mL IL-1α (IL-1α group), 10 ng/mL IL-1α + 10 µM Dex (Dex group), or 10 ng/mL IL-1α + 10 µg/mL anti-CD147 antibody (anti-CD147 group). Evaluations of FLSs proliferation, cell cycle, migration, gene expression of Cyclin D1, p27, p57, interleukin (IL)-1ß, IL-6, IL-17, tumor necrosis factor (TNF)-α, CD147, CypB, matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-13, ROS generation, protein expression of NF-κB and CD147, and translocation of NF-κB p65 were all conducted. The in vivo results showed that arthritis intensity was attenuated in the Dex-treated group. The in vitro findings demonstrated that treatment with Dex induced G0/G1 arrest and suppressed proliferation, migration, gene expression of IL-1ß, IL-6, IL-17, TNF-α, CD147, CypB, MMP-3, MMP-9, and MMP-13, ROS generation and protein expression of NF-κB and CD147. Translocation of NF-κB p65 was inhibited by both Dex and anti-CD147 monoclonal antibody treatment. We offer molecular evidence of the anti-rheumatism efficacy Dex through hindrance to CD147, splendidly stabilization of the oxidative stress by downregulating the NF-κB signaling pathway.

CypB-CD147 Signaling Is Involved in Crosstalk between Cartilage and FLS in Collagen-Induced Arthritis.

To investigate the crosstalk between cartilage and fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), we adopted an in vitro coculture system model of collagen-induced arthritis (CIA) cartilage and CIA FLS monolayer. CIA rat samples of the synovium and femur head were collected for isolation of FLS and coculture system. Cartilages were treated with vehicle (Ctrl group), 10 ng/mL interleukin- (IL-) 1α (IL-1α group), and 10 ng/mL IL-1α plus 10 µM dexamethasone (Dex group) for 3 days before coculture with FLS for further 2 days. After the coculture, FLS were collected to determine the influences of articular cartilage on synoviocytes. Whether the CypB-CD147 signaling pathway is involved in the interactions between cartilage and FLS is assayed. Results showed that IL-1α-stimulated CIA cartilage promoted the proliferation and reduced the apoptosis of FLS. Increased inflammatory cytokines and decreased p57 expression were found in cocultured FLS stimulated by IL-1α-challenged CIA cartilage. Upregulation of NF-κB and I-κB kinase ß (IKK-ß) and downregulation of the inhibitor of NF-κBα (I-κBα) protein were observed in cocultured FLS. After coculture, significant increases in the expression of cyclophilin B (CypB) and CD147 were observed in CIA cartilage and FLS, respectively. Furthermore, results of immunofluorescence staining showed that the anti-CD147 antibody significantly suppressed p65 nuclear translocation in cocultured FLS stimulated by IL-1α-challenged CIA cartilage. In conclusion, inflammatory effects in the cartilage-FLS coculture system are associated with the CypB-CD147 mediating NF-κB pathway which may further enhance the inflammation in RA.

Broadband and high-resolution electro-optic dual-comb interferometer with frequency agility.

We propose a broadband and high-resolution dual-comb interferometer (DCI) realized with dense electro-optic frequency combs (EOFCs), which are generated with two-stage electro-optic modulation and nonlinear fiber spectral broadening. The broadband coarse comb is generated in the first-stage modulation and the space between neighboring combs is filled with a dense electrical comb in the second-stage modulation. The spectral resolution of the DCI can be flexibly changed from 10 MHz to 1 GHz easily as required, and electro-optic DCIs with 10-MHz, 100-MHz, and 1-GHz frequency resolutions are experimentally realized. Meanwhile, DCI working in the quasi-integer-ratio mode is easily implemented in this system for the increased refresh rate and improved figure of merit especially for high resolution. As a demonstration, 150000 comb lines with 10 MHz frequency interval are resolved in the experiment.

Fast MHz spectral-resolution dual-comb spectroscopy with electro-optic modulators.

Frequency-agile dual-comb spectroscopy (DCS) with electro-optic modulators (EOMs) promises to facilitate the implementation of DCS in many environmental applications. In this Letter, we demonstrate a 1 MHz resolution electro-optic dual-comb system with a measurement speed of 20 kHz. We generate an electro-optic frequency comb (EOFC) consisting of 50000 teeth with 1 MHz line spacing. Each comb tooth is well resolved by another EOFC with 2.5 GHz line spacing. We record transmittances of high Q-factor resonators within milliseconds. Our figure of merit is shown to be 36 times more sensitive than a configuration that would beat two combs of 1 MHz spacing.

Pharmacological modulation of melanocortin-4 receptor by melanocortin receptor accessory protein 2 in Nile tilapia.

The melanocortin-4 receptor (MC4R) acts as a member of G-protein coupled receptors and participate in food intake and energy expenditure. Melanocortin 2 receptor accessory protein 2 (MRAP2) plays a critical role in regulating MC4R signaling in mammals and zebrafish. However, evidence on their interaction in other teleost species remains elusive. Here, we cloned and assessed the evolutionary aspect and pharmacological modulation of MRAP2 on MC4R signaling in Nile tilapia (Oreochromis niloticus). Tissue distribution analysis of tmc4r and tmrap2 confirmed their co-expression in the brain region. tMRAP2 protein could form antiparallel homo-dimer and directly interacted with tMC4R in vitro and presence of tMRAP2 led to the reduction of agonist response and surface expression of tMC4R. Overall, our findings provide a comparative overview on the evolutionary conservation, genomic distribution, tissue-specific expression and pharmacological profile of the MC4R and MRAP2 in another non-mammalian teleost.

HDAC5 integrates ER stress and fasting signals to regulate hepatic fatty acid oxidation.

Disregulation of fatty acid oxidation, one of the major mechanisms for maintaining hepatic lipid homeostasis under fasting conditions, leads to hepatic steatosis. Although obesity and type 2 diabetes-induced endoplasmic reticulum (ER) stress contribute to hepatic steatosis, it is largely unknown how ER stress regulates fatty acid oxidation. Here we show that fasting glucagon stimulates the dephosphorylation and nuclear translocation of histone deacetylase 5 (HDAC5), where it interacts with PPARα and promotes transcriptional activity of PPARα. As a result, overexpression of HDAC5 but not PPARα binding-deficient HDAC5 in liver improves lipid homeostasis, whereas RNAi-mediated knockdown of HDAC5 deteriorates hepatic steatosis. ER stress inhibits fatty acid oxidation gene expression via calcium/calmodulin-dependent protein kinase II-mediated phosphorylation of HDAC5. Most important, hepatic overexpression of a phosphorylation-deficient mutant HDAC5 2SA promotes hepatic fatty acid oxidation gene expression and protects against hepatic steatosis in mice fed a high-fat diet. We have identified HDAC5 as a novel mediator of hepatic fatty acid oxidation by fasting and ER stress signals, and strategies to promote HDAC5 dephosphorylation could serve as new tools for the treatment of obesity-associated hepatic steatosis.

Linear optical sampling technique for simultaneously characterizing WDM signals with a single receiving channel.

Wavelength-division multiplexing (WDM) schemes have greatly increased optical transmission capacity, especially when using massively parallel optical frequency combs (OFCs) as carriers. In this paper, we show that linear optical sampling (LOS) is a kind of multiheterodyne process and it can be performed with arbitrary-shaped periodic waveforms. Meanwhile, it can be used for characterizing WDM signals with only a single receiving channel. We successfully demonstrate an observation of 40 WDM channels with 1 THz total bandwidth and total 800 Gbit/s data rate by only using one sampling channel. We show that the adoption of the concept of multiheterodyne detection can improve the performance of LOS technique, and can also greatly simplify multi-channel WDM monitoring systems.

Hybrid dual-comb interferometer with easily established mutual coherence and a very high refresh rate.

In this Letter, we propose a hybrid dual-comb interferometer (DCI) with a free-running mode-locked laser and an electro-optic frequency comb. The mutual coherence of this DCI is achieved by using an injection locking technique without any complicated phase-locking loops or post data processing algorithms. The proposed architecture is validated by resolving more than 10,000 comb lines of 250 MHz spacing with a refresh rate of 500 kHz. This combination of two kinds of optical frequency comb sources is suitable for wideband spectroscopic applications, where moderate spectral resolutions as well as high refresh rates are necessary.