Hypoxia-sensing VGLL4 promotes LDHA-driven lactate production to ameliorate neuronal dysfunction in a cellular model relevant to Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease where abnormal amyloidogenic processing of amyloid-ß precursor protein (APP) occurs and has been linked to neuronal dysfunction. Hypometabolism of glucose in the brain can lead to synaptic loss and neuronal death, which in turn exacerbates energy deficiency and amyloid-ß peptide (Aß) accumulation. Lactate produced by anaerobic glycolysis serves as an energy substrate supporting neuronal function and facilitating neuronal repair. Vestigial-like family member 4 (VGLL4) has been recognized as a key regulator of the hypoxia-sensing pathway. However, the role of VGLL4 in AD remains unexplored. Here, we reported that the expression of VGLL4 protein was significantly decreased in the brain tissue of AD model mice and AD model cells. We further found that overexpression of VGLL4 reduced APP amyloidogenic processing and ameliorated neuronal synaptic damage. Notably, we identified a compromised hypoxia-sensitive capability of LDHA regulated by VGLL4 in the context of AD. Upregulation of VGLL4 increased the response of LDHA to hypoxia and enhanced the expression levels of LDHA and lactate by inhibiting the ubiquitination and degradation of LDHA. Furthermore, the inhibition of lactate production by using sodium oxamate, an inhibitor of LDHA, suppressed the neuroprotective function of VGLL4 by increasing APP amyloidogenic processing. Taken together, our findings demonstrate that VGLL4 exerts a neuroprotective effect by upregulating LDHA expression and consequently promoting lactate production. Thus, this study suggests that VGLL4 may be a novel player involved in molecular mechanisms relevant for ameliorating neurodegeneration.

Inhibiting NLRP3 inflammasome signaling pathway promotes neurological recovery following hypoxic-ischemic brain damage by increasing p97-mediated surface GluA1-containing AMPA receptors.

BACKGROUND: The nucleotide-binding oligomeric domain (NOD)-like receptor protein 3 (NLRP3) inflammasome is believed to be a key mediator of neuroinflammation and subsequent secondary brain injury induced by ischemic stroke. However, the role and underlying mechanism of the NLRP3 inflammasome in neonates with hypoxic-ischemic encephalopathy (HIE) are still unclear. METHODS: The protein expressions of the NLRP3 inflammasome including NLRP3, cysteinyl aspartate specific proteinase-1 (caspase-1) and interleukin-1ß (IL-1ß), the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid receptor (AMPAR) subunit, and the ATPase valosin-containing protein (VCP/p97), were determined by Western blotting. The interaction between p97 and AMPA glutamate receptor 1 (GluA1) was determined by co-immunoprecipitation. The histopathological level of hypoxic-ischemic brain damage (HIBD) was determined by triphenyltetrazolium chloride (TTC) staining. Polymerase chain reaction (PCR) and Western blotting were used to confirm the genotype of the knockout mice. Motor functions, including myodynamia and coordination, were evaluated by using grasping and rotarod tests. Hippocampus-dependent spatial cognitive function was measured by using the Morris-water maze (MWM). RESULTS: We reported that the NLRP3 inflammasome signaling pathway, such as NLRP3, caspase-1 and IL-1ß, was activated in rats with HIBD and oxygen-glucose deprivation (OGD)-treated cultured primary neurons. Further studies showed that the protein level of the AMPAR GluA1 subunit on the hippocampal postsynaptic membrane was significantly decreased in rats with HIBD, and it could be restored to control levels after treatment with the specific caspase-1 inhibitor AC-YVAD-CMK. Similarly, in vitro studies showed that OGD reduced GluA1 protein levels on the plasma membrane in cultured primary neurons, whereas AC-YVAD-CMK treatment restored this reduction. Importantly, we showed that OGD treatment obviously enhanced the interaction between p97 and GluA1, while AC-YVAD-CMK treatment promoted the dissociation of p97 from the GluA1 complex and consequently facilitated the localization of GluA1 on the plasma membrane of cultured primary neurons. Finally, we reported that the deficits in motor function, learning and memory in animals with HIBD, were ameliorated by pharmacological intervention or genetic ablation of caspase-1. CONCLUSION: Inhibiting the NLRP3 inflammasome signaling pathway promotes neurological recovery in animals with HIBD by increasing p97-mediated surface GluA1 expression, thereby providing new insight into HIE therapy.

Data-driven inverse design of mode-locked fiber lasers.

The diverse applications of mode-locked fiber lasers (MLFLs) raise various demands on the output of the laser, including the pulse duration, energy, and shape. Simulation is an excellent method to guide the design and construction of an MLFL for on-demand laser output. Traditional simulation of an MLFL uses the split-step Fourier method (SSFM) to solve the nonlinear Schrödinger (NLS) equation, which suffers from high computational complexity. As a result, the inverse design of MLFLs via the traditional SSFM-based simulation method relies on the design experience. Here, a completely data-driven approach for the inverse design of MLFLs is proposed, which significantly reduces the computational complexity and achieves a fast automatic inverse design of MLFLs. We utilize a recurrent neural network to realize fast and accurate MLFL modeling, then the desired cavity settings meeting the output demands are searched via a deep-reinforcement learning algorithm. The results prove that the data-driven method enables the accurate inverse design of an MLFL to produce a preset target femtosecond pulse with a certain duration and pulse energy. In addition, the cavity settings generating soliton molecules with different target separations can also be located via the data-driven inverse design. With the GPU acceleration, the time consumption of the data-driven inverse design of an MLFL is less than 1.3 hours. The proposed data-driven approach is applicable to guide the inverse design of an MLFL to meet the different demands of various applications.

Spectral broadening scheme for suppressing SBS effects based on time-domain optimized chirp-like signals.

We propose a novel (to our knowledge) driving scheme to suppress the stimulated Brillouin scattering (SBS) effect in master oscillator power amplification (MOPA) systems based on an external high-order phase modulation. Since seed sources with the linear chirp can uniformly broaden the SBS gain spectrum with a high SBS threshold, a chirp-like signal was designed by applying further editing and processing to the piecewise parabolic signal. Compared with the traditional piecewise parabolic signal, the chirp-like signal has similar linear chirp characteristics and can reduce the driving power and sampling rate requirements, enabling more efficient spectral spreading. The SBS threshold model is constructed theoretically based on the three-wave coupling equation. The spectrum modulated by the chirp-like signal is compared with the flat-top and Gaussian spectra in terms of the SBS threshold and the bandwidth-distribution normalized threshold, and a considerable improvement is demonstrated. Meanwhile, the experimental validation is carried out in a watt-class amplifier based on the MOPA structure. At a 3 dB bandwidth of ∼10 GHz, the SBS threshold of the seed source modulated by the chirp-like signal is improved by 35% compared to the flat-top spectrum and 18% compared to the Gaussian spectrum, respectively, and the normalized threshold is also the highest among them. Our study shows that the SBS suppression effect is not only related to the power distribution of the spectrum but also can be improved by the time domain design, which provides a new idea for analyzing and improving the SBS threshold of narrow-linewidth fiber lasers.

Digital pre-distortion using a Gauss-Newton-based direct learning architecture for coherent optical transmitters.

Digital pre-distortion (DPD) is a powerful technique to mitigate transmitter nonlinear distortion in optical transmissions. In this Letter, the identification of DPD coefficients based on the direct learning architecture (DLA) using the Gauss-Newton (GN) method is applied in optical communications for the first time. To the best of our knowledge, this is the first time that the DLA has been realized without training an auxiliary neural network to mitigate optical transmitter nonlinear distortion. We describe the principle of the DLA using the GN method and compare the DLA with the indirect learning architecture (ILA) that uses the least-square (LS) method. Extensive numerical and experimental results indicate that the GN-based DLA is superior to the LS-based ILA, especially in a low signal-to-noise ratio scenario.

Signal-to-noise ratio degradation analysis for optoelectronic feedback-based chaotic optical communication systems.

Chaotic optical communication encrypts transmitted signals through physical noise; this ensures high security while causing a certain decrease in the signal-to-noise ratio (SNR). Thus, it is necessary to analyze the SNR degradation of decrypted signals after chaotic encryption and the minimum requirements for the SNR of the fiber channel to meet the required bit error rate (BER) performance. Accordingly, an SNR model of decrypted signals for optoelectronic feedback-based chaotic optical communication systems is proposed. Under different channel SNRs, the SNR degradation of 40 Gbit/s phase chaos and intensity chaos models is investigated by simulation and experiment, respectively, with a 15 GHz wideband chaotic carrier. Comparing decrypted signals with original signals, the simulation results show that there is a 2.9 dB SNR degradation for both intensity chaos and phase chaos. Further, in experiments, SNR degradation from 4.5 dB to 5.6 dB, with various channel SNRs for intensity chaos, is analyzed, while there is an SNR degradation from 7.1 dB to 8.3 dB for phase chaos. The simulation and experimental results provide guidance for long-distance transmission chaotic optical communication systems.

Low-complexity amplitude-division irregular QAM formats for short-reach unamplified coherent optical systems.

A low-complexity scheme is proposed to realize irregular uniform quadrature amplitude modulation (QAM) formats with Gray mapping, which are named amplitude-division irregular QAM (AD-Ir-QAM) formats. Compared to conventional probabilistic shaping (PS) with the Maxwell-Boltzmann (MB) distribution (PS-MB), irregular QAM formats show a smaller peak-to-average power (PAPR) and achieve a better performance in systems with the peak-power constraint. Compared with irregular QAM formats realized by PS (PS-Ir-QAM), AD-Ir-QAM formats realize a more flexible rate adaptation and have a lower implementation complexity. Experimental results obtained in an unamplified coherent optical system show that, at a generalized mutual information (GMI) of 4.5 bits/2D-symbol, AD-Ir-100QAM achieves gains of 2.1 and 0.5 dB in the power budget over PS-MB-100QAM and PS-Ir-100QAM, respectively.

High-power narrow-linewidth fiber lasers using optical spectrum broadening based on high-order phase modulation of inversion probability-tuning sequence.

Continuous fiber laser with ultra-high power and narrow linewidth is one of the key devices in the field of high-precision industrial processing, beam combining, and nonlinear frequency conversion. Under the premise of ensuring the signal quality, continuously increasing the output power is the focus of high-power narrow-linewidth fiber lasers. Driven by the white noise or pseudo-random binary sequence (PRBS), using cascaded phase modulations to broaden the spectrum of the seed source to suppress the stimulated Brillouin scattering (SBS) effect in the master oscillator power amplifier (MOPA) structure is an effective solution to increase the output power. However, this type of optical spectrum needs to be optimized, and the randomness of the driving signal causes a self-pulsing effect, which limits the further increase of the output power. In this paper, the influence of the frequency interval and randomness of the driving signal on the SBS effect in the laser system is analyzed. The modulated spectral type can be simply adjusted through changing the bit rate and inversion probability. Combining with high-order phase modulation, an approximate rectangular spectral broadening of the seed source with a tunable bandwidth up to 30 GHz is achieved. Compared with the cascaded white noise case, the output power of this scheme is increased by 600 W under the extended bandwidth of 27 GHz. It is fully verified that the seed source spectrum with high in-band flatness and low randomness can effectively suppress the SBS effect in the fiber laser and increase the output power.

Low-complexity full-field ultrafast nonlinear dynamics prediction by a convolutional feature separation modeling method.

The modeling and prediction of the ultrafast nonlinear dynamics in the optical fiber are essential for the studies of laser design, experimental optimization, and other fundamental applications. The traditional propagation modeling method based on the nonlinear Schrödinger equation (NLSE) has long been regarded as extremely time-consuming, especially for designing and optimizing experiments. The recurrent neural network (RNN) has been implemented as an accurate intensity prediction tool with reduced complexity and good generalization capability. However, the complexity of long grid input points and the flexibility of neural network structure should be further optimized for broader applications. Here, we propose a convolutional feature separation modeling method to predict full-field ultrafast nonlinear dynamics with low complexity and strong generalization ability with high accuracy, where the linear effects are firstly modeled by NLSE-derived methods, then a convolutional deep learning method is implemented for nonlinearity modeling. With this method, the temporal relevance of nonlinear effects is substantially shortened, and the parameters and scale of neural networks can be greatly reduced. The running time achieves a 94% reduction versus NLSE and an 87% reduction versus RNN without accuracy deterioration. In addition, the input pulse conditions, including grid point numbers, durations, peak powers, and propagation distance, can be generalized accurately during the predicting process. The results represent a remarkable improvement in ultrafast nonlinear dynamics prediction and this work also provides novel perspectives of the feature separation modeling method for quickly and flexibly studying the nonlinear characteristics in other fields.

Optical filtering impairment monitoring based on model fusion for optical networks.

Reconfigurable optical add-and-drop multiplexer (ROADM) is a key element in optical networks. As several ROADMs are cascaded over long paths, the penalty induced by ROADM has become non-negligible due to the tight optical filtering. In this case, for efficient and reliable network planning and operation, accurate monitoring of optical filtering penalty is very important. In this paper, we propose a real-time optical filtering monitoring scheme based on model fusion. We combine an analytical model based on the digital communications theory of band-limited channels with linear equalization and a data-driven model implemented using artificial neural network (ANN). The scheme can achieve high accuracy and interpretability. Moreover, since the input features are extracted from configuration parameters and receiver digital signal processing (DSP), no additional devices are needed, which is attractive for practical deployment. Extensive simulations and experiments are conducted to investigate the performance of the scheme, and the results show the superior performance.

Asymmetric point-to-multipoint coherent architecture with a frequency aliasing recovery algorithm for cost-constraint short-reach access networks.

An asymmetric point-to-multipoint (PTMP) coherent architecture combined with a frequency aliasing recovery (FAR) algorithm is proposed for cost-constraint short-reach access networks. In this architecture, the uplink transmitters are simplified significantly with the uplink dual-polarization four-level pulse amplitude modulation (DP-PAM4) and downlink DP quadrature phase shift keying (DP-QPSK) asymmetric transmission design. Digital to analog converters (DACs) and radio frequency (RF) drivers are reduced by half, and in-phase and quadrature modulators (IQMs) are replaced by Mach-Zehnder modulators (MZMs), saving four MZ interferometers (MZIs). Furthermore, based on the asymmetric architecture, the FAR algorithm can recover signals from frequency aliasing caused by frequency offset (FO), even when half of the signal spectrum is aliased. This algorithm enables the asymmetric architecture to narrow down guard bands between subcarriers or even overlap the subcarriers, saving the receiver bandwidth at the aggregation/hub side. The performance of the asymmetric uplink DP-PAM4 transmission with the FAR algorithm is evaluated in both simualations and experiments. The effects of laser linewidths and IQ skew on the performance of the FAR algorithm are also analyzed. Simulation results show the algorithm can recover 16 Gbaud and 32 Gbaud signal from 8 GHz and 16 GHz aliasing, respectively. In the experiments with 10 km fiber transmissions, the FAR algorithm can recover 10 Gbaud signals from 5 GHz frequency aliasing, saving about 20.83% of the total receiver bandwidth in a 2-subcarrier system.

Coherent digital-analog radio-over-fiber (DA-RoF) system with a CPRI-equivalent data rate beyond 1 Tb/s for fronthaul.

We propose and experimentally demonstrate a coherent digital-analog radio-over-fiber (DA-RoF) system and achieve the transmission of Tb/s common public radio interface (CPRI)-equivalent data rate for fronthaul. The proposed coherent DA-RoF system includes DA-RoF modulation, demodulation and DA-RoF compatible coherent digital signal processing (DSP) blocks. A theoretical analysis of the DA-RoF scheme together with parameter optimization is accomplished as well. In the experiment, a 25 Gbaud DA-RoF signal with 1 Tb/s CPRI-equivalent data rate is transmitted in the system, satisfying the error vector magnitude (EVM) requirement for 256-quadrature amplitude modulation (QAM) signal transmission. With the symbol rate reduced to 10 Gbaud, an EVM below 2.5% is achieved, which meets the requirement for 1024-QAM transmission. The experimental results show that the coherent DA-RoF system is a promising solution for future fronthaul.

Modeling of a multi-parameter chaotic optoelectronic oscillator based on the Fourier neural operator.

A model construction scheme of chaotic optoelectronic oscillator (OEO) based on the Fourier neural operator (FNO) is proposed. Different from the conventional methods, we learn the nonlinear dynamics of OEO (actual components) in a data-driven way, expecting to obtain a multi-parameter OEO model for generating chaotic carrier with high-efficiency and low-cost. FNO is a deep learning architecture which utilizes neural network as a parameter structure to learn the trajectory of the family of equations from training data. With the assistance of FNO, the nonlinear dynamics of OEO characterized by differential delay equation can be modeled easily. In this work, the maximal Lyapunov exponent is applied to judge whether these time series have chaotic behavior, and the Pearson correlation coefficient (PCC) is introduced to evaluate the modeling performance. Compare with long and short-term memory (LSTM), FNO is not only superior to LSTM in modeling accuracy, but also requires less training data. Subsequently, we analyze the modeling performance of FNO under different feedback gains and time delays. Both numerical and experimental results show that the PCC can be greater than 0.99 in the case of low feedback gain. Next, we further analyze the influence of different system oscillation frequencies, and the generalization ability of FNO is also analyzed.

Coherent chaotic optical communication of 30 Gb/s over 340-km fiber transmission via deep learning.

Chaotic optical communication has attracted much attention as a hardware encryption method in the physical layer. Limited by the requirements of chaotic hardware synchronization, fiber transmission impairments are restrictedly compensated in the optical domain. There has been little experimental demonstration of high-speed and long-distance chaotic optical communication systems. Here, we propose a method to overcome such limitations. Using a deep-learning model to realize chaotic synchronization in the digital domain, fiber transmission impairments can be compensated by digital-signal processing (DSP) algorithms with coherent detection. A successful transmission of 30 Gb/s quadrature phase-shift keying messages hidden in a 15 GHz wideband chaotic optical carrier was experimentally demonstrated over a 340-km fiber link. Meanwhile, the chaotic receiver can be significantly simplified without compromising security. The proposed method is a possible way to promote the practical application of chaotic optical communications.

Low-complexity Volterra-inspired neural network equalizer in 100-G band-limited IMDD PON system.

One of the most promising solutions for 100 Gb/s line-rate passive optical networks (PONs) is intensity modulation and direct detection (IMDD) technology together with a digital signal processing- (DSP-) based equalizer for its advantages of system simplicity, cost-effectiveness, and energy-efficiency. However, due to restricted hardware resources, the effective neural network (NN) equalizer and Volterra nonlinear equalizer (VNLE) have the drawback of high implementation complexity. In this paper, we incorporate an NN with the physical principles of a VNLE to construct a white-box low-complexity Volterra-inspired neural network (VINN) equalizer. This equalizer has better performance than a VNLE at the same complexity and attains similar performance with much lower complexity than a VNLE with optimized structural hyperparameter. The effectiveness of the proposed equalizer is verified in 1310 nm band-limited IMDD PON systems. A 30.5-dB power budget is achieved with the 10-G-class transmitter.

SOA pattern effect mitigation by neural network based pre-equalizer for 50G PON.

Semiconductor optical amplifier (SOA) is widely used for power amplification in O-band, particularly for passive optical networks (PONs) which can greatly benefit its advantages of simple structure, low power consumption and integrability with photonics circuits. However, the annoying nonlinear pattern effect degrades system performance when the SOA is needed as a pre-amplifier in PONs. Conventional solutions for pattern effect mitigation are either based on optical filtering or gain clamping. They are not simple or sufficiently flexible for practical deployment. Neural network (NN) has been demonstrated for impairment compensation in optical communications thanks to its powerful nonlinear fitting ability. In this paper, for the first time, NN-based equalizer is proposed to mitigate the SOA pattern effect for 50G PON with intensity modulation and direct detection. The experimental results confirm that the NN-based equalizer can effectively mitigate the SOA nonlinear pattern effect and significantly improve the dynamic range of receiver, achieving 29-dB power budget with the FEC limit at 1e-2. Moreover, the well-trained NN model in the receiver side can be directly placed at the transmitter in the optical line terminal to pre-equalize the signal for transmission so as to simplify digital signal processing in the optical network unit.

Demonstration of a 50G-PON with a 45-dB power budget using an IQ-interleaved coherent detection scheme.

The application of traditional coherent detection technology to optical access networks has been undermined due to its high complexity and high cost. In this paper, we propose a novel IQ-interleaved detection method which uses the preset frequency offset of the lasers at the transmitter and receiver to obtain the in-phase and quadrature components of the received signal. It keeps the simple structure of heterodyne detection and avoids the down-conversion process. Without Nyquist pulse shaping, the received signal bandwidth of the proposed scheme is theoretically 0.5B smaller than that of heterodyne detection for signal with a symbol rate of B. The 50-Gb/s NRZ transmission experiment proves that by using the proposed scheme, the receiving sensitivity and the frequency drift tolerance can be improved by ∼1 dB and 1 GHz compared with heterodyne detection under strong bandwidth limitation. Without pulse shaping, the receiving sensitivity, frequency drift tolerance (1-dB sensitivity penalty) and link power budget for 20-km fiber transmission are -31.8 dBm, 11 GHz and 43.5 dB, respectively. A higher power budget of 45 dB can be achieved when Nyquist pulse shaping is applied. The proposed scheme provides a low-complexity potential solution for a next-generation coherent PON.

Ultra-fast RSOP tracking via 3 pilot tones for short-distance coherent SCM systems.

We propose an algorithm to track the rotation of state of polarization (RSOP) for short-distance coherent subcarrier-multiplexing systems. 3 pilot tones are used to estimate RSOP matrices on a block-by-block basis and recover phase noise as well. An ultra-fast RSOP tracking ability using the proposed algorithm is demonstrated by experiment. Specifically, the bit error rate increases from 2.3×10-3 to 5.6×10-3 when the RSOP speed increases from 0 rad/s to 50 Mrad/s. We also demonstrate the robustness of the algorithm against polarization mode dispersion and polarization dependent loss.

Frequency-offset-tolerant optical frequency comb-based coherent transmission for intra-datacenter interconnections.

In recent years, in order to increase the capacity and scalability of intra-datacenter (DC) transmission, the optical frequency comb (OFC) source has been considered promising to replace discrete lasers, aiming to reduce the cost of wavelength division multiplexing (WDM) transmission within DC. In this paper, an OFC based coherent architecture is proposed. An OFC, in the receiver side, is split by a splitter with a uniform power ratio and separately used as local oscillators (LOs) to detect the demultiplexed signals. The signal spectrum is copied onto every tone of the LO-OFC, and a large frequency offset (FO) tolerance is achieved. In addition, the required ADC sampling rate is the same as a system without FO. Extensive simulations are conducted. In the simulated coherent WDM transmission system, a 3-tone-OFC is used to provide 3 carriers, and an 11-tone-OFC is split and used to provide LO-OFCs. For a 64GBd polarization multiplexing 16 quadrature amplitude modulation (PM-16QAM) WDM transmission, the tolerances of FO are up to about ±0.3THz and ±0.374THz for the 1st/3rd signal, and the 2nd signal, respectively, below the pre-forward error correction (FEC) bit error rate (BER) level of 1.25×10-2. Moreover, the maximum tolerance of FO linearly increases with the number of effective tones in LO-OFC. Further, extensive experiments with back-to-back connection are conducted to verify the performance. The tolerance of FO is up to >36 GHz for 36GBd PM-16QAM transmission with a 3-tone-LO-OFC below the BER level of 1.25×10-2. The proposed OFC based coherent architecture is a promising solution for intra-DC interconnections with a large FO.

FPGA-based digital chaotic anti-interference lidar system.

We use the chaotic signal generated by a field-programmable gate array (FPGA) to establish a digital chaotic pulse lidar system, which can achieve mid-range detection and high ranging accuracy without a complex optical structure. We employ the FPGA to generate random sequences with different modulation rates based on different chaotic iterative equations and initial values. By selecting the initial value and improved logistic equations, we successfully achieve centimeter-level ranging accuracy. Experiments have proved that the digital chaotic lidar system can effectively resist the interference of chaotic signals, square wave signals, and sine wave signals with modulation frequencies of 10 MHz, 100 MHz, 200 MHz, and 1 GHz, showing its strong anti-interference capability.