Quercetin in Osteoporosis Treatment: A Comprehensive Review of Its Mechanisms and Therapeutic Potential.

PURPOSE OF REVIEW: This review aims to provide a theoretical basis and insights for quercetin's clinical application in the prevention and treatment of osteoporosis (OP), analyzing its roles in bone formation promotion, bone resorption inhibition, anti-inflammation, antioxidant effects, and potential mechanisms. RECENT FINDINGS: OP, a prevalent bone disorder, is marked by reduced bone mineral density and impaired bone architecture, elevating the risk of fractures in patients. The primary approach to OP management is pharmacotherapy, with quercetin, a phytochemical compound, emerging as a focus of recent interest. This natural flavonoid exerts regulatory effects on bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts and promotes bone health and metabolic equilibrium via anti-inflammatory and antioxidative pathways. Although quercetin has demonstrated significant potential in regulating bone metabolism, there is a need for further high-quality clinical studies focused on medicinal quercetin.

Systematic DOE Approach for Dry Granulation Study at Early Clinical Stage of Novel Drugs: An Industrial Case.

In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.

Real-time adaptive optical self-interference cancellation for in-band full-duplex transmission using SARSA(λ) reinforcement learning.

Self-interference (SI) due to signal leakage from a local transmitter is an issue in an in-band full-duplex (IBFD) transmission system, which would cause severe distortions to a receiving signal of interest (SOI). By superimposing a local reference signal with the same amplitude and opposite phase, the SI signal can be fully canceled. However, as the manipulation of the reference signal is usually operated manually, it is difficult to ensure a high speed and high accurate cancellation. To overcome this problem, a real-time adaptive optical SI cancellation (RTA-OSIC) scheme using a SARSA(λ) reinforcement learning (RL) algorithm is proposed and experimentally demonstrated. The proposed RTA-OSIC scheme can automatically adjust the amplitude and phase of a reference signal by adjusting a variable optical attenuator (VOA) and a variable optical delay line (VODL) achieved through an adaptive feedback signal, which is generated by evaluating the quality of the received SOI. To verify the feasibility of the proposed scheme, a 5 GHz 16QAM OFDM IBFD transmission experiment is demonstrated. By using the proposed RTA-OSIC scheme, for an SOI at three different bandwidths of 200, 400, and 800 MHz, the signal can be adaptively and correctly recovered within 8 time periods (TPs), which is the required time of a single adaptive control step. The cancellation depth for the SOI with a bandwidth of 800 MHz is 20.18 dB. The short- and long-term stability of the proposed RTA-OSIC scheme is also evaluated. The experimental results indicate that the proposed approach could be a promising solution for real-time adaptive SI cancellation in future IBFD transmission systems.

Broadband photonic-assisted microwave receiver with high cross-channel interference suppression and image rejection.

A broadband photonic-assisted microwave receiver with high cross-channel interference suppression and image rejection is proposed and experimentally demonstrated. At the input of the microwave receiver, a microwave signal is injected into an optoelectronic oscillator (OEO), which functions as a local oscillator (LO) to generate a low-phase noise LO signal as well as a photonic-assisted mixer to down-convert the input microwave signal to the intermediate frequency (IF). A microwave photonic filter (MPF), realized by the joint operation of a phase modulator (PM) in the OEO and a Fabry-Perot laser diode (FPLD), is used as a narrowband filter to select the IF signal. Thanks to the wide bandwidth of the photonic-assisted mixer and the wide frequency tunable range of the OEO, the microwave receiver can support broadband operation. The high cross-channel interference suppression and image rejection are enabled by the narrowband MPF. The system is evaluated experimentally. A broadband operation from 11.27 to 20.85 GHz is demonstrated. For a multi-channel microwave signal with a channel spacing of 2 GHz, a cross-channel interference suppression ratio of 21.95 dB and an image rejection ratio of 21.51 dB are realized. The spurious-free dynamic range (SFDR) of the receiver is also measured to be 98.25 dB·Hz2/3. The performance of the microwave receiver for multi-channel communications is also experimentally evaluated.

Dual-loop parity-time symmetric system with a rational loop length ratio.

By exploring the relationship between the gain/loss and the coupling coefficient, parity-time (PT) symmetry has been well explored in the photonics and optoelectronics fields to achieve unique functions, such as sidemode suppression, non-reciprocal light propagation, and unidirectional invisibility. In general, a PT-symmetric system has an architecture with two identical coupled resonators or loops. In this Letter, we explore the possibility of implementing a PT-symmetric system having an architecture with one resonator having a loop length that is a rational number of times the length of the other resonator, to increase the sidemode suppression ratio. A theoretical analysis is performed, which is validated by a proof-of-concept experiment in which a fiber ring laser having two loops with a length ratio being a rational number of 200/3, supporting single-longitudinal-mode lasing at 1555.88 nm, is demonstrated. Thanks to the non-identical loop lengths, the sidemode suppression ratio is increased, which is 53.2 dB in the experiment.

Simple polarization-insensitive coherent RoF link with increased capacity.

A simple polarization-insensitive coherent radio-over-fiber (RoF) link with increased spectrum efficiency and transmission capacity is proposed and demonstrated. Instead of using two polarization splitters (PBSs), two 90° hybrids, and four pairs of balanced photodetectors (PDs) in a conventional polarization-diversity coherent receiver (PDCR), a simplified PDCR with only one PBS, one optical coupler (OC), and two PDs is employed in the coherent RoF link. At the simplified receiver, a novel, to the best of our knowledge, digital signal processing (DSP) algorithm is proposed to achieve polarization-insensitive detection and demultiplexing of two spectrally overlapping microwave vector signals as well as the elimination of the joint phase noise originating from the transmitter and the local oscillator (LO) laser sources. An experiment is performed. The transmission and detection of two independent 16QAM microwave vector signals at identical microwave carrier frequencies of 3 GHz with a symbol rate of 0.5 GSym/s over a 25-km single-mode fiber (SMF) is demonstrated. Thanks to the spectrum superposition of the two microwave vector signals, the spectral efficiency as well as the data transmission capacity is increased.

Non-orthogonal multiple access in a radio over fiber link based on optical-domain power allocation.

Non-orthogonal multiple access (NOMA) in a radio over fiber (RoF) link based on optical-domain power allocation is proposed and demonstrated. The NOMA is implemented at the RoF transmitter where two spectrum-overlapped microwave vector signals with an identical power level are modulated on an optical carrier to generate two orthogonally polarized optical signals. By passing the optical signals through a polarization controller (PC) and a polarizer, the power levels of the two optical signals are controlled to achieve optical power allocation (OPA). The optical signals are then transmitted over a fiber to the receiver. Since the power levels of the two microwave vector signals applied to the modulator are identical and the power allocation is implemented in the optical domain, the nonlinearity due to the higher-power input microwave vector signal is reduced, leading to an increase in the dynamic range. At the receiver, the two optical signals are detected at a photodetector (PD). To demultiplex the two microwave vector signals, a digital signal processing (DSP) algorithm is developed. The proposed approach is evaluated experimentally. The results show that the transmission performance in terms of error vector magnitude (EVM) is improved thanks to the increased dynamic range.

Subacute thyroiditis presenting as simple acute headache was misdiagnosed as meningitis: case report and literature review.

BACKGROUND: The relationship between headache and thyrotoxicosis has been occasionally mentioned in case reports, but there are few related reports. Thus, the relationship cannot be determined. Few cases of subacute thyroiditis (SAT) presenting as simple headache have been reported. CASE PRESENTATION: This case report describes a middle-aged male patient who came to our hospital with acute headache for 10 days. He was initially misdiagnosed as meningitis due to headache, fever, and increased C-reactive protein. Routine antibacterial and antiviral therapy did not improve his symptoms. Blood test suggested thyrotoxicosis, and color ultrasound suggested SAT sonography. He was diagnosed with SAT. With the treatment of SAT, the headache was relieved after the thyrotoxicosis improved. CONCLUSION: This patient is the first detailed report of SAT presenting with simple headache, which is helpful for clinicians to differentiate and diagnose atypical SAT.

Methyl cinnamate protects against dextran sulfate sodium-induced colitis in mice by inhibiting the MAPK signaling pathway.

Effective and non-toxic therapeutic agents are lacking for the prevention and treatment of colitis. Previous studies found that methyl cinnamate (MC), extracted from galangal ( Alpinia officinarum Hance), has anti-inflammatory properties. However, whether MC is effective as anti-colitis therapy remains unknown. In this study, we investigate the therapeutic effects of MC on dextran sulfate sodium (DSS)-induced colitis in mice and further explore its potential mechanism of action. MC treatment relieves symptoms associated with DSS-induced colitis, including the recovery of DSS-induced weight loss, decreases the disease activity index score, and increases the colon length without toxic side effects. MC treatment protects the integrity of the intestinal barrier in mice with DSS-induced colitis and inhibits the overexpression of pro-inflammatory cytokines in vivo and in vitro. Moreover, the MAPK signaling pathway is found to be closely related to the treatment with MC of colitis. Western blot analysis show that phosphorylation of the p38 protein in colon tissues treated with MC is markedly reduced and phosphorylation levels of the p38, JNK and ERK proteins are significantly decreased in RAW 264.7 cells treated with MC, indicating that the mechanism of MC in treating DSS-induced colitis could be achieved by inhibiting the MAPK signaling pathway. Furthermore, 16S RNA sequencing analysis show that MC can improve intestinal microbial dysbiosis in mice with DSS-induced colitis. Altogether, these findings suggest that MC may be a novel therapeutic candidate with anti-colitis efficacy. Furthermore, MC treatment relieves the symptoms of colitis by inhibiting the MAPK signaling pathway and improving the intestinal microbiota.

Microwave photonic link to transmit four microwave vector signals on a single optical carrier based on coherent detection and digital signal processing.

A microwave photonic link to transmit four independent microwave vector signals modulated on a single optical carrier based on coherent detection and digital signal processing (DSP) is proposed and experimentally demonstrated. At the transmitter, a continuous-wave (CW) light wave is modulated by four independent microwave vector signals with an identical center microwave frequency at a dual-polarization dual-drive Mach-Zehnder modulator (DP-DDMZM), to generate four intensity-modulated optical signals, with two signals sharing one of the two orthogonal polarization states. After transmission over a single-mode fiber (SMF), the optical signals are applied to a polarization- and phase- diversity coherent receiver to which a light wave from a second laser source as a local oscillator (LO) is also applied. To eliminate the joint phase noise and the unstable offset frequency from the transmitter and the LO laser sources and to perform polarization demultiplexing, a digital noise cancellation algorithm and a polarization demultiplexing algorithm are developed. The proposed approach is evaluated experimentally. For four independent 16 quadrature amplitude modulation (16-QAM) microwave vector signals at 4 GHz with a symbol rate of 0.5 GSymbol/s, error-free transmission over a 9-km SMF is achieved when the received optical power at the coherent receiver is higher than -21 dBm with forward error correction (FEC).

Single-mode narrow-linewidth fiber ring laser with SBS-assisted parity-time symmetry for mode selection.

A single-longitudinal-mode narrow-linewidth fiber ring laser with stimulated Brillouin scattering (SBS) assisted parity-time (PT) symmetry for mode selection in a single fiber loop is proposed and experimentally demonstrated. When an optical pump is launched into the fiber loop along one direction, an SBS gain for the Stokes light along the opposite direction is produced. For two light waves at the Stokes frequency propagating along the two opposite directions, one will have a net gain and the other will have a net loss. By incorporating a fiber Bragg grating (FBG) with partial reflection in the loop, mutual coupling between the two counterpropagating Stokes light waves is achieved. The SBS gain can be controlled by tuning the angle between the polarization directions of the pump and the Stokes light waves through a polarization controller (PC). Once the gain and loss coefficients between the two counterpropagating light waves are controlled to be identical in magnitude, and that the gain coefficient is greater than the coupling coefficient caused by the FBG, PT symmetry breaking is achieved, making the mainmode to sidemode ratio highly enhanced, single mode lasing is thus achieved. The approach is evaluated experimentally. For a fiber ring laser with a cavity length of 8.02 km, single-mode lasing with a narrow 3-dB linewidth of 368 Hz and a sidemode suppression ratio of around 33 dB is demonstrated. The wavelength tunable range from 1550.02 to 1550.18 nm is also demonstrated.

Photonic generation of a microwave waveform with an ultra-long temporal duration using a frequency-shifting dispersive loop.

A photonic approach to generate a linearly chirped microwave waveform (LCMW) with an ultra-long temporal duration is proposed and experimentally demonstrated. The microwave waveform generation is achieved based on spectral-shaping and wavelength-to-time (SS-WTT) mapping by using a Mach-Zehnder interferometer (MZI) and a frequency-shifting dispersive loop (FSDL), respectively. To make the generated microwave waveform have an ultra-long temporal duration, the FSDL is operating to allow a spectrally shaped optical pulse to recirculate in a dispersive loop multiple times with a low propagating loss, to generate a microwave waveform with a temporal duration that is more than one order of magnitude longer than that of a microwave waveform generated using a dispersive element without recirculation. To generate a LCMW, the spectral shaper is configured to have a free spectral range (FSR) that is linearly increasing or decreasing with optical wavelength. The proposed approach is experimentally demonstrated. Two LCMWs, by allowing an optical pulse recirculating in the FSDL for three and seven round trips, tripled and septupled temporal durations of 64 and 182 ns are generated. The generation of two LCMWs with ultra-long temporal durations of 370 ns and 450 ns are also demonstrated.

Optoelectronic oscillator with improved sidemode suppression by joint use of spectral Vernier effect and parity-time symmetry.

An optoelectronic oscillator (OEO) with improved sideband suppression by joint use of the spectral Vernier effect and parity-time (PT) symmetry is proposed and experimentally demonstrated. The spectral Vernier effect is implemented using two mutually coupled loops with different loop lengths, to increase the effective free spectral range (FSR). To further increase the mode selection capability to ensure stable single-frequency oscillation with an increased sidemode suppression ratio (SMSR), PT symmetry is implemented, in which the two mutually coupled loops are controlled with balanced gain and loss. Thanks to the combined effects, stable single-mode oscillation with a significantly increased SMSR is achieved. The proposed OEO is studied theoretically and evaluated experimentally. The results show that for a generated microwave signal at 10 GHz, the SMSR is 67.68 dB, which is increased by 11.20 dB or 26.05 dB, when using only the spectral Vernier effect or only the PT symmetry. Thanks to the long length of the longer loop, good phase noise performance is still maintained. The measurement shows that a phase noise as low as -124.5 dBc/Hz at an offset frequency of 10 kHz is achieved.

Optical processor for a binarized neural network.

We propose and experimentally demonstrate an optical processor for a binarized neural network (NN). Implementation of a binarized NN involves multiply-accumulate operations, in which positive and negative weights should be implemented. In the proposed processor, the positive and negative weights are realized by switching the operations of a dual-drive Mach-Zehnder modulator (DD-MZM) between two quadrature points corresponding to two binary weights of +1 and -1, and the multiplication is also performed at the DD-MZM. The accumulation operation is realized by dispersion-induced time delays and detection at a photodetector (PD). A proof-of-concept experiment is performed. A binarized convolutional neural network (CNN) accelerated by the optical processor at a speed of 32 giga floating point operations/s (GFLOPS) is tested on two benchmark image classification tasks. The large bandwidth and parallel processing capability of the processor has high potential for next generation data computing.

Multi-task photonic time-delay reservoir computing based on polarization modulation.

We propose and experimentally demonstrate a multi-task photonic time-delay reservoir computing (RC) system based on polarization modulation. The key component in the system is a polarization modulator (PolM) that functions, jointly with a polarization controller (PC) and a polarizer, as an equivalent Mach-Zehnder modulator (MZM) to perform electrical to optical conversion and to provide nonlinear operation. By adjusting the bias of the equivalent MZM, the nonlinear function can be optimized for different tasks to achieve the best multi-task performance. In this paper, the task-independent information processing capacity (IPC) of the time-delay RC system is evaluated. The results show that the readout bias of the equivalent MZM leads to a different IPC which can be optimized for different tasks. Two benchmark tasks (NARMA10 and IPIX radar signal prediction) are performed experimentally. The readout bias is adjusted independently for each of the two tasks to give a minimum normalized mean square error (NMSE), which are 0.2103 and 0.0031 for the NARMA10 and IPIX radar signal prediction tasks at a speed of 1.06 Mb/s, respectively.

Parity-time-symmetric optoelectronic oscillator based on higher-order optical modulation.

An optoelectronic oscillator (OEO) for single-frequency microwave generation, enabled by broken parity time (PT) symmetry based on higher-order modulation using a Mach-Zehnder modulator, is proposed and demonstrated. Instead of using two physically separated mutually coupled loops with balanced gain and loss, the PT symmetry is realized using a single physical loop to implement two equivalent loops with the gain loop formed by the beating between the optical carrier and the ±1st-order sidebands and the loss loop formed by the beating between the ±1st-order sidebands and the ±2nd-order sidebands at a photodetector. The gain and loss coefficients are made identical in magnitude by controlling the incident light power to the modulator and the modulator bias voltage. Once the gain/loss coefficient is greater than the coupling coefficient, the PT symmetry is broken, and a single-frequency oscillation without using an ultra-narrow passband filter is achieved. The approach is evaluated experimentally. For an OEO with a loop length of 10.1 km, a single-frequency microwave signal at 9.997 GHz with a 55-dB sidemode suppression ratio and -142-dBc/Hz phase noise at a 10-kHz offset frequency is generated. No mode hopping is observed during a 5-hour measurement period.

Microwave frequency measurement using a silicon integrated microring resonator.

Photonics-assisted instantaneous frequency measurement of a microwave signal using a silicon integrated microring resonator (MRR) is proposed and experimentally demonstrated. The frequency of a microwave signal has a unique relationship with the power ratio between the two microwave signals at the outputs of two microwave photonic filters (MPF) with complementary frequency responses. The key device to implement the MPFs is a silicon integrated MMR, which is employed to convert a phase-modulated optical signal to an intensity-modulated optical signal by placing two optical carriers at the complementary slopes of the MRR. For a given frequency measurement range and resolution, an MRR is designed and fabricated, and its use for instantaneous microwave frequency (IMF) measurement is implemented. For the fabricated MRR, an IMF measurement range of 14-25 GHz with a measurement accuracy of ±0.2GHz is achieved.

Low jitter microwave pulse train generation based on an optoelectronic oscillator.

We demonstrate an approach to ultra-short pulse train generation with a low time jitter based on pulse compression of a frequency comb generated by a dual-loop optoelectronic oscillator (OEO). The proposed dual-loop OEO consists of two feedback loops, with one having a long loop length and the other a short loop length. In the long loop, a phase modulator (PM) cascaded with a Mach-Zehnder modulator (MZM) are employed, and in the short loop, only the MZM is included. Due to the Vernier effect, the use of the dual-loop structure can facilitate mode selection to generate a single-frequency microwave carrier with multiple optical sidebands corresponding to an optical comb. By adjusting the phase relationship between the optical sidebands using a dispersion compensating fiber (DCF), a stable optical pulse train is generated. Thanks to the low phase noise nature of an OEO, the generated pulse train has a low time jitter. The proposed approach is evaluated experimentally. A pulse train with a repetition frequency of 2.023 GHz and a pulse width of 40 ps is generated. The single-sideband (SSB) phase noise of the carrier frequency generated by the OEO is measured to be -118 dBc/Hz at a 10-kHz offset frequency, corresponding to a time jitter of the pulse train of 391.2 fs. The phase noise can be further reduced if an active cavity stabilization mechanism is adopted, enabling further reduction in the time jitter to the order of tens of femtoseconds.

Parity-time-symmetric frequency-tunable optoelectronic oscillator with a single dual-polarization optical loop.

We propose and experimentally demonstrate a parity-time (PT)-symmetric frequency-tunable optoelectronic oscillator (OEO) in which the PT symmetry is implemented based on a single dual-polarization optical loop. By employing the inherent birefringence of a z-cut lithium niobate (LiNbO3) phase modulator (PM), two mutually coupled optoelectronic loops supporting orthogonally polarized light waves with one experiencing a gain and the other a loss are implemented. By controlling the gain, loss, and the coupling coefficients between the two loops, the PT symmetry breaking condition is met, which enables the OEO to operate in single mode without using an ultranarrow passband optical or microwave filter. The frequency tunability is realized using a microwave photonic filter (MPF) implemented using the PM and a phase-shifted fiber Bragg grating (PS-FBG). The proposed PT-symmetric OEO is experimentally evaluated. A stable and frequency-tunable microwave signal from 2 to 12 GHz is generated. The phase noise of the generated signal at 11.8 GHz is measured, which is -124dBc/Hz at a frequency offset of 10 kHz.

Observation of PT-symmetry in a fiber ring laser.

A wavelength-tunable single-mode laser with a sub-kilohertz linewidth based on parity-time (PT)-symmetry is proposed and experimentally demonstrated. The proposed PT-symmetric laser is implemented based on a hybrid use of an optical fiber loop and a thermally tunable integrated microdisk resonator (MDR). The MDR, implemented based on the silicon-on-insulator, operates with the optical fiber loop to form two mutually coupled cavities with an identical geometry. By controlling two light waves passing through the two cavities, with one having a gain coefficient and the other a loss coefficient but with an identical magnitude, a PT-symmetric laser is implemented. Thanks to an ultranarrow passband of the cavity due to PT-symmetry, single-longitudinal mode lasing is achieved. The tuning of the wavelength is implemented by thermally tuning the MDR. The proposed PT-symmetric laser is demonstrated experimentally. Single-longitudinal mode lasing at a wavelength of around 1555 nm with a sub-kilohertz linewidth of 433 Hz is implemented. The lasing wavelength is continuously tunable from 1555.135 to 1555.887 nm with a tuning slope of 75.24 pm/°C.