Brevilin A is a potent anti-metastatic CRC agent that targets the VEGF-IL6-STAT3 axis in the HSCs-CRC interplay.

BACKGROUND: More than half of the colorectal cancer (CRC) patients will develop liver metastasis that underlies the cancer mortality. In the hepatic tumor microenvironment, the interplay between CRC cells and hepatic stellate cells (HSCs), and the activation of HSCs to become carcinoma-associated fibroblasts (CAFs) will further promote the cancer development. Nevertheless, the critical signaling molecule that involved in these processes remains unknown, which hinders the development of effective therapeutic agents for the treatment of metastatic CRC (mCRC). METHODS: Conditioned medium system and co-cultured system were used to examine the interplay between CRC cells and HSCs. Luminex liquid suspension chip detection and enzyme-linked immunosorbent assay were used to screen for the mediators in the conditioned medium that facilitated the CRC-HSCs interplay and HSCs-to-CAFs differentiation. Cell and animal models were used to examine whether brevilin A inhibited CRC liver metastasis via the VEGF-IL6-STAT3 axis. RESULTS: In the CRC-HSCs interplay, CRC promoted HSCs-to-CAFs differentiation by releasing vascular endothelial growth factor (VEGF); and HSCs released interleukin 6 (IL6) that activated signal transducer and activator of transcription 3 (STAT3) in the CRC and hence increased the cancer metastatic potential. The functions of the VEGF-IL6-STAT3 axis in the HSCs-CRC interplay were further validated by VEGF recombinant protein and IL6 neutralizing antibody. More importantly, brevilin A, an active compound isolated from Centipeda minima (L.) A. Br. et Aschers, targeted the VEGF-IL6-STAT3 axis in the CRC-HSCs interplay, hence significantly inhibited colorectal liver metastasis and cancer growth both in vitro and in vivo. CONCLUSIONS: We are the first to demonstrate brevilin A possesses potent anti-mCRC effect by targeting the VEGF-IL6-STAT3 axis in the CRC-HSCs interplay. Our findings not only support the development of brevilin A as a novel therapeutic agent for mCRC treatment, but also pave the path for the development of other VEGF-IL6-STAT3 targeting therapeutic strategies.

Performance of polar coded probabilistic shaped PAM8 with systematic interleaver and identically distributed pilot in weak turbulence.

In this paper, for the first time to the best of our knowledge, we investigate the experiment of polar coded probabilistic shaped 8-ary pulse amplitude modulation (PS-PAM8) in weak turbulence. A systematic interleaver (SIL) is proposed to improve the polar code performance for PS-PAM8, compatible with the 5 G channel coding standard. Considering the effects of turbulence and shaped constellations, the pilot with identical distributions as the transmitted data is used for dynamic channel estimation to avoid demodulation failure. Moreover, the application of hybrid equalization with nonlinear and linear equalizers effectively reduces the receiver sensitivity. In 25 GBd transmission over a 4 m free-space link, the transmission performance of polar coded PAM8 schemes with SIL is better than that of the low-density parity check code by 1.0 dB, and the power budget is further saved by 0.72∼0.83 dB after linear equalization. Meanwhile, the shaping gains of polar coded PS-PAM8 with SIL and hybrid equalization are up to 2.0 dB at 1.5 bits/channel use. In addition, different weak turbulence conditions can be generated inside a chamber, and the observed channel fading is consistent with the log-normal model. The results show that the proposed polar coded PS scheme can improve the Q-factor by 0.49∼1.74 dB in different turbulence conditions.

Dexmedetomidine Protects against Airway Inflammation and Airway Remodeling in a Murine Model of Chronic Asthma through TLR4/NF-κB Signaling Pathway.

Asthma is a common respiratory disease characterized by chronic airway inflammation. Dexmedetomidine (DEX), a highly selective α2 adrenergic receptor agonist, has been shown to participate in regulating inflammatory states and thus exert organ protective actions. However, the potential of DEX in asthma is still unknown. This study is aimed at investigating the role of DEX in a mouse model of house dust mite- (HDM-) induced asthma and exploring its underlying mechanism. Here, we found that DEX treatment significantly ameliorated airway hyperresponsiveness, airway inflammation, and airway remodeling in the asthmatic mice, which were similar to the efficacy of the reference anti-inflammatory drug dexamethasone. In addition, DEX reversed the increased expression of toll-like receptor 4 (TLR4) and its downstream signaling adaptor molecule nuclear factor-κB (NF-κB) in the lung tissue of asthmatic mice. Furthermore, these protective effects of DEX were abolished by yohimbine, an α2 adrenergic receptor antagonist. These results indicate that DEX is capable of ameliorating airway inflammation and remodeling in asthmatic mice, and this protective effect is associated with the inhibition of the TLR4/NF-κB signaling pathway.

Probabilistically shaped polar-coded MIMO-FSO communication systems with spatially correlated fading.

In this paper, the probabilistically shaped polar-coded multiple-input multiple-output free-space optical (MIMO-FSO) communication system with or without spatially correlated (SC) fading is investigated to improve transmission performance. The designed shaping-polar encoder can flexibly generate three typical shapes of distribution via shaping bits and be decoded in the conventional method. The achievable information rate (AIR) of MIMO-FSO systems with or without SC fading is evaluated to determine the number of shaping bits for the shaping-polar encoder. The non-pairwise distributions are demonstrated to be more suitable for turbulence channels than other distributions. The results show that the AIR of the shaped 4 × 4 systems even exceeds that of the uniform 4 × 5 systems in the low signal-to-noise ratio regions over strong turbulence channels. In terms of bit error rate performance, more than 15 dB shaping gains can be achieved by the shaped 4 × 4 systems compared to the uniform single-input single-output polar-coded systems. In addition, the shaped 4 × 4 systems outperform the uniform ones ranging from 1 dB to 1.9 dB over different atmospheric turbulence channels with or without SC fading, comparable to the uniform MIMO systems with one more physical receiver.

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.

Targeting visualization of malignant tumor based on the alteration of DWI signal generated by hTERT promoter-driven AQP1 overexpression.

PURPOSE: To specifically diagnose malignant tumors in DWI using the human telomerase reverse transcriptase (hTERT) promoter-driven AQP1 expression. METHODS: The human telomerase reverse transcriptase (hTERT) promoter-driven AQP1 gene overexpression lentivirus system (hTERT-AQP1) and cytomegalovirus (CMV) promoter-driven AQP1 gene overexpression lentivirus system (CMV-AQP1) were prepared, and transduced into telomerase-positive and -negative cells. The AQP1 expression and DWI signal intensity (SI) change in transduced cells were analyzed. Balb/C nude mice subcutaneous xenograft models derived from lentivirus-transduced telomerase-positive and -negative cells were used to evaluate AQP1 expression and DWI SI change in vivo. We further established another group of subcutaneous xenograft model using pristine telomerase-positive and -negative cells, followed by injecting the lentiviral vectors intratumorally or intravenously, to determine the malignant tumor-targeted imaging of hTERT-AQP1. RESULTS: The hTERT-AQP1 and CMV-AQP1 were successfully prepared. After transduction, hTERT-AQP1 could induce the specific overexpression of AQP1 in telomerase-positive cells. Compared with untransduced cells, all CMV-AQP1-pretransduced cells and hTERT-AQP1-pretransduced telomerase-positive cells showed decreased SI and increased apparent diffusion coefficient (ADC) in DWI, while hTERT-AQP1-pretransduced telomerase-negative cells showed no obvious SI and ADC change. Correspondingly, hTERT-AQP1-transduced telomerase-positive tumors and CMV-AQP1-transduced telomerase-positive and -negative tumors showed decreased DWI SI and increased ADC, while hTERT-AQP1-transduced telomerase-negative tumor had no SI and ADC changes. After intratumoral or intravenous injection, CMV-AQP1 could upregulate AQP1 expression and induce DWI SI and ADC alteration in both telomerase-positive and -negative tumors, while hTERT-AQP1 worked in telomerase-positive tumors specifically. CONCLUSION: Cancers can be specifically visualized based on the DWI signal alteration which triggered by hTERT-AQP1 lentivirus system that combined AQP1 gene and hTERT promoter.

Real-time IBFD transmission system based on adaptive optical self-interference cancellation using the hybrid criteria regular triangle algorithm.

In this Letter, we first propose and demonstrate a real-time in-band full duplex (IBFD) transmission system based on adaptive optical self-interference cancellation (OSIC). The field programmable gate array (FPGA) is used for high-speed and real-time orthogonal frequency-division multiplexing (OFDM) transmission. The hybrid criteria regular triangle (RT) algorithm is first proposed to combine signal power and the bit error rate (BER) together as the objective function to realize the adaptive control process. With this algorithm, the real-time adaptive OSIC system is able to converge and fully recover the signal of interest (SOI) within 12 sampling times, which is by far the fastest, to the best of our knowledge, convergence under the real-time transmission scenario. Experiments show that the system can achieve 28 dB cancellation depth across 0-1.45 GHz wideband, and 40 dB cancellation depth at 900 MHz, 2.4 GHz, and 5 GHz, which is the best cancellation performance in current real-time adaptive OSIC schemes and shows the potential of our system in different commercial applications.

Polar coded probabilistic amplitude shaping for the free space optical atmospheric turbulence channel.

In this paper, the polar coded probabilistic amplitude shaping (PC-PAS) is investigated in a free space optical (FSO) communication system to combat the fading induced by turbulence. The achievable rate of multiple level coding (MLC) and bit-interleaved coded modulation (BICM) schemes with different distributions are studied in turbulence channels, which proves that the non-uniform distribution can achieve larger achievable rates than the uniform distribution in the FSO turbulence channel. And the PC-PAS techniques based on MLC and BICM are both investigated. For MLC-based PC-PAS, the dynamically frozen bits scheme is adopted and the modification to the labeling rule is proposed to label the non-negative constellation points. For the BICM-based PC-PAS, the exchange scheme is proposed to combine the polar codes and PAS technique. The Block error rate (BLER) is evaluated by the Monte Carlo simulation method. From the results, both the MLC-based and the BICM-based PC-PAS can improve the performance compared to the uniform distribution. And the PC-PAS based on MLC outperforms the PC-PAS based on BICM in the same turbulence condition.

Neural network decoder of polar codes with tanh-based modified LLR over FSO turbulence channel.

The deep learning-based decoder of polar codes is investigated over free space optical (FSO) turbulence channel for the first time. The feedforward neural networks (NN) are adopted to establish the decoder and some custom layers are designed to train the NN decoder over the turbulence channel. The tanh-based modified log-likelihood ratio (LLR) is proposed as the input of NN decoder, which has faster convergence and better bit error rate (BER) performance compared with the standard LLR input. The simulation results show that the BER performance of NN decoder with tanh-based modified LLR is close to the conventional successive cancellation list (SCL) decoder over the turbulence channel, which verifies that the NN decoder with tanh-based modified LLR can learn the encoding rule of polar codes and the characteristics of turbulence channel. Furthermore, the turbulence-stability is investigated and the trained NN decoder in a fixed turbulence condition also has stable performance in other turbulence conditions.

Hybrid wideband multipath self-interference cancellation with an LMS pre-adaptive filter for in-band full-duplex OFDM signal transmission.

A wideband multipath self-interference cancellation (SIC) system employing both dual-drive Mach-Zehnder modulator-based analog SIC and least mean square (LMS) algorithm-based pre-adaptive filter digital SIC is proposed and demonstrated for the cancellation of multipath self-interference (SI) and facilitation of in-band full-duplex (IBFD) orthogonal frequency-division multiplexing (OFDM) signal transmission. The multipath effect is an unavoidable challenge in SIC due to the dynamic and unpredictable properties in each path, as well as the need for separate matching components for compensating for each path. In this Letter, an LMS algorithm-based adaptive filter is used as a pre-equalizer to adapt and generate the matching signal to the closest approximate of the multipath SI signal. The adaptation is based on the minimization of the error signal generated from the matching signal and multipath SI signal in the LMS algorithm. With the introduction of the LMS adaptive filter to the analog SIC, an additional 9 dB cancellation improvement is obtained, resulting in a total of 32 dB cancellation depth over a cancellation bandwidth of 2.7 GHz at a center frequency of 1.65 GHz. To the best of our knowledge, the achieved performance is by far the widest cancellation bandwidth in a multipath SIC system, which is essential in a large bandwidth and high data rate transmission system. With the help of the proposed LMS adaptive filter digital SIC assisted analog SIC located at the remote node, power-efficient IBFD transmission of an OFDM signal through a 25 km fiber is experimentally demonstrated with a 6 dB bit error rate and 8% error vector magnitude improvements.

Adaptive over-the-air RF self-interference cancellation using a signal-of-interest driven regular triangle algorithm.

An optically-enabled radio frquency (RF) self-interference cancellation system is demonstrated for over-the-air in-band full duplex transmission, based on a signal-of-interest (SOI) driven regular triangle algorithm. Since the goal of a self-interference cancellation system is to retrieve the SOI that is masked by the in-band interference signal, using the SOI quality as the driven parameter for optimizing the self-interference cancellation performance is a natural and effective way to allow the system to adapt to changes and obtain the best cancellation performance. Since regular triangle algorithm has short iteration time, bursts of pseudo-random binary sequence would be used between real data transmission for optimizing the self-interference cancellation performance. The adaptive regular triangle algorithm optimizes the cancellation setting such that the in-band interference can be cancelled to a minimum, i.e., down to the noise floor. During the over-the-air experiment, 22 dB of cancellation depth is obtained over a 300 MHz bandwidth at 18.35 GHz without the need of digital self-interference cancellation.

Adaptive optical self-interference cancellation for in-band full-duplex systems using regular triangle algorithm.

In this paper, we propose an adaptive optical self-interference cancellation using regular triangle algorithm for in-band full-duplex systems. By using this algorithm, the manual adjustment of the tunable optical time delay line and attenuator is replaced with the adaptive program to change the delay and attenuation for achieving optimal cancellation point. The adjustment process is simplified as a convex function problem. We choose to attain the optimal cancellation point by directly and continuously sampling the power of the signal after cancellation and in turn adjust the time delay and attenuation according to the algorithm. In this way, the two paths in the self-interference cancellation system are precisely and automatically matched. By using our proposed algorithm, the interference signal over 300-MHz wideband is diminished to the noise floor, attaining 20-25 dB cancellation depth adaptively. Compared with other existing algorithms in both the experiment and simulation, our proposed regular triangle algorithm reaches the optimal point faster with 10-30% less number of samples from the near start region, and lowers 40-60% less number of samples from the farther start region.

Kernel mapping for mitigating nonlinear impairments in optical short-reach communications.

Nonlinear impairments induced by the opto-electronic components are one of the fundamental performance-limiting factors in high-speed optical short-reach communications, significantly hindering capacity improvement. This paper proposes to employ a kernel mapping function to map the signals in a Hilbert space to its inner product in a reproducing kernel Hilbert space, which has been successfully demonstrated to mitigate nonlinear impairments in optical short-reach communication systems. The operation principle is derived. An intensity modulation/direct detection system with 1.5-µm vertical cavity surface emitting laser and 10-km 7-core fiber achieving 540.68-Gbps (net-rate 505.31-Gbps) has been carried out. The experimental results reveal that the kernel mapping based schemes are able to realize comparable transmission performance as the Volterra filtering scheme even with a high order.

Spectrally efficient digitized radio-over-fiber system with k-means clustering-based multidimensional quantization.

We propose a spectrally efficient digitized radio-over-fiber (D-RoF) system by grouping highly correlated neighboring samples of the analog signals into multidimensional vectors, where the k-means clustering algorithm is adopted for adaptive quantization. A 30 Gbit/s D-RoF system is experimentally demonstrated to validate the proposed scheme, reporting a carrier aggregation of up to 40 100 MHz orthogonal frequency division multiplexing (OFDM) channels with quadrate amplitude modulation (QAM) order of 4 and an aggregation of 10 100 MHz OFDM channels with a QAM order of 16384. The equivalent common public radio interface rates from 37 to 150 Gbit/s are supported. Besides, the error vector magnitude (EVM) of 8% is achieved with the number of quantization bits of 4, and the EVM can be further reduced to 1% by increasing the number of quantization bits to 7. Compared with conventional pulse coding modulation-based D-RoF systems, the proposed D-RoF system improves the signal-to-noise-ratio up to ∼9 dB and greatly reduces the EVM, given the same number of quantization bits.

Nonlinearity-aware 200 Gbit/s DMT transmission for C-band short-reach optical interconnects with a single packaged electro-absorption modulated laser.

We experimentally demonstrate the transmission of a 200 Gbit/s discrete multitone (DMT) at the soft forward error correction limit in an intensity-modulation direct-detection system with a single C-band packaged distributed feedback laser and traveling-wave electro absorption modulator (DFB-TWEAM), digital-to-analog converter and photodiode. The bit-power loaded DMT signal is transmitted over 1.6 km standard single-mode fiber with a net rate of 166.7 Gbit/s, achieving an effective electrical spectrum efficiency of 4.93 bit/s/Hz. Meanwhile, net rates of 174.2 Gbit/s and 179.5 Gbit/s are also demonstrated over 0.8 km SSMF and in an optical back-to-back case, respectively. The feature of the packaged DFB-TWEAM is presented. The nonlinearity-aware digital signal processing algorithm for channel equalization is mathematically described, which improves the signal-to-noise ratio up to 3.5 dB.

Performance analysis of an optical self-interference cancellation system with a directly modulated laser-based demonstration.

In this paper, two main performance indices of the optical self-interference cancellation (OSIC) system are theoretically analyzed: cancellation bandwidth and depth. Delay deviation is investigated to be the determining factor of cancellation bandwidth, based on which the bandwidth advantage of the OSIC system over electrical schemes is also proven theoretically. Cancellation depth in the narrowband is mostly influenced by attenuation and delay-adjusting deviation, while in the broadband case, the performance is mostly limited by frequency-dependent amplitude and phase mismatch. The cancellation performance analysis is suitable for most linear modulation-demodulation OSIC systems, including the directly modulated laser (DML)-based OSIC system verified experimentally in this paper. The cancellation model is well demonstrated by the agreement between experimental cancellation results and predicted performance. For over-the-air demonstration with the employment of antennas, broadband cancellation within 450 MHz bandwidth of 22 dB and 25 dB is achieved at 900 MHz and 2.4 GHz, respectively. In addition, orthogonal frequency division multiplexing signals are employed to show in-band full-duplex transmission with good performance by the DML-based OSIC system, with successful suppression of self-interference and recovery of the signal of interest.

Performance investigation of the polar coded FSO communication system over turbulence channel.

In this paper, for the first time, to the best of our knowledge, polar codes are introduced and experimentally implemented in a free space optical (FSO) communication system to combat atmospheric turbulence induced fading. By analyzing the characteristics of the turbulence channel, a method of evaluating the channel state information for polar decoding is proposed that can achieve good trade-off between the performance and the computational complexity of this polar coded system. To verify our scheme, an intensity modulation direct detection FSO communication experimental platform with a turbulence chamber is established. For the weak turbulence condition, comparing with the low-density parity check codes, the experimental results show that our proposed scheme has stronger error correcting capacity and lower computational complexity in combating the turbulence induced fading. Moreover, for moderate and strong turbulence conditions, the gamma-gamma turbulence model is adopted for constructing the Monte Carlo simulation. The results of the experiment and simulation both show that our proposed scheme can effectively combat atmospheric turbulence induced fading with a relatively low computational complexity in a wide range of turbulence conditions.

High performance and cost effective CO-OFDM system aided by polar code.

A novel polar coded coherent optical orthogonal frequency division multiplexing (CO-OFDM) system is proposed and demonstrated through experiment for the first time. The principle of a polar coded CO-OFDM signal is illustrated theoretically and the suitable polar decoding method is discussed. Results show that the polar coded CO-OFDM signal achieves a net coding gain (NCG) of more than 10 dB at bit error rate (BER) of 10-3 over 25-Gb/s 480-km transmission in comparison with conventional CO-OFDM. Also, compared to the 25-Gb/s low-density parity-check (LDPC) coded CO-OFDM 160-km system, the polar code provides a NCG of 0.88 dB @BER = 10-3. Moreover, the polar code can relieve the laser linewidth requirement massively to get a more cost-effective CO-OFDM system.

Digital mobile fronthaul employing differential pulse code modulation with suppressed quantization noise.

A differential pulse code modulation (DPCM) based digital mobile fronthaul architecture is proposed and experimentally demonstrated. By using a linear predictor in the DPCM encoding process, the quantization noise can be effectively suppressed and a prediction gain of 7~8 dB can be obtained. Experimental validation is carried out with a 20 km 15-Gbaud/λ 4-level pulse amplitude modulation (PAM4) intensity modulation and direct detection system. The results verify the feasibility of supporting 163, 122, 98, 81 20-MHz 4, 16, 64, 256 QAM based antenna-carrier (AxC) containers with only 3, 4, 5, 6 quantization bits at a sampling rate of 30.72MSa/s in LTE-A environment. Further increasing the number of quantization bits to 8 and 9, 1024 quadrature amplitude modulation (1024 QAM) and 4096 QAM transmission can be realized with error vector magnitude (EVM) lower than 1% and 0.5%, respectively. The supported number of AxCs in the proposed DPCM-based fronthaul is increased and the EVM is greatly reduced compared to the common public radio interface (CPRI) based fronthaul that uses pulse code modulation. Besides, the DPCM-based fronthaul is also experimentally demonstrated to support universal filtered multicarrier signal that is one candidate waveform for the 5th generation mobile systems.

Experimental study of wideband in-band full-duplex communication based on optical self-interference cancellation.

In this paper, we experimentally demonstrate and study a wideband in-band full-duplex (IBFD) wireless communication system based on optical self-interference cancellation (SIC). The optical SIC performances based on antennas for broadband IBFD are firstly evaluated within high frequency bands (> 10GHz). In this system, two electro-absorption-modulated lasers (EMLs) and a balanced photo-detector (BPD) are employed to remove the wideband self-interference within received wireless signal. By theoretical derivation and experimental verification, the impact factors of SIC are analyzed, especially for non-flatness wireless channel case. Experimental results show more than 30-dB cancellation depth in 100-MHz bandwidth with employment of horn antennas. Besides, IBFD transmission performance based on OFDM signals for different bandwidth with 11.15-GHz center frequency is also demonstrated, and ~52.2- dB•Hz2/3 spurious-free dynamic range (SFDR) is obtained.