TS-2021, a third-generation oncolytic adenovirus that carried Ki67 promoter, TGF-ß2 5'UTR, and IL-15 against experimental glioblastoma.

Oncolytic virotherapy is a promising therapeutic approach for glioblastoma (GBM) treatment, although the outcomes are partially satisfactory. Hence, more effective strategies are needed urgently to modify therapeutic viruses to enhance their efficiency and safety in killing tumor cells and improve the survival rate of GBM patients. This study generated a new-generation oncolytic adenovirus Ad5 KT-E1A-IL-15 (TS-2021) and evaluated its antitumor efficacy. Ex vivo analyses revealed Ki67 and TGF-ß2 co-localized in GBM cells. In addition, TS-2021 selectively replicated in GBM cells, which was dependent on the expression of Ki67 and TGF-ß2. The immunocompetent mice model of GBM demonstrated the in vivo efficacy of TS-2021 by inhibiting tumor growth and improving survival proficiently. Notably, TS-2021 effectively reduced MMP3 expression by inactivating the MKK4/JNK pathway, thereby reducing tumor invasiveness. Altogether, the findings of the present study highlight that TS-2021 can effectively target GBM cells expressing high levels of Ki67 and TGF-ß2, exerting potent antitumor effects. Additionally, it can improve efficacy and suppress tumor invasiveness by inhibiting the MKK4/JNK/MMP3 pathway. Thus our study demonstrates the efficiency of the novel TS-2021 in the mouse model and provides a potential therapeutic option for patients with GBM.

Neural-network-based end-to-end learning for adaptive optimization of two-dimensional signal generation in UVLC systems.

Visible light communication (VLC) benefits from the underwater blue-green window and holds immense potential for underwater wireless communication. In order to address the limitations of various equipment and harsh channel conditions in the underwater visible light communication (UVLC) system, the researchers proposed to use the method of autoencoder (AE) to tap the potential of the system. However, traditional AE schemes involve replacing the transmitting and receiving components of a communication system with a large multilayer perceptron (MLP) network, and they have significant drawbacks due to their reliance on a single network structure. In this paper, a novel 2D adaptive optimization autoencoder (2D-AOAE) framework is proposed to realize adaptive modulation and demodulation of two-dimensional signals. By implementing this scheme, we experimentally achieved a transmission rate of 2.85 Gbps over a 1.2-meter underwater VLC link. Compared to the traditional 32QAM UVLC system, the 2D-AOAE scheme demonstrated a 15.4% data rate increase. Moreover, the 2D-AOAE scheme exhibited a remarkable 73% improvement when compared to the UVLC system utilizing the traditional AE scheme. This significant enhancement highlights the superior performance and capabilities of the 2D-AOAE scheme in terms of transmission rate.

Feature decoupled knowledge distillation enabled lightweight image transmission through multimode fibers.

Multimode fibers (MMF) show tremendous potential in transmitting high-capacity spatial information. However, the quality of multimode transmission is quite sensitive to inherent scattering characteristics of MMF and almost inevitable external perturbations. Previous research has shown that deep learning may break through this limitation, while deep neural networks are intricately designed with huge computational complexity. In this study, we propose a novel feature decoupled knowledge distillation (KD) framework for lightweight image transmission through MMF. In this framework, the frequency-principle-inspired feature decoupled module significantly improves image transmission quality and the lightweight student model can reach the performance of the sophisticated teacher model through KD. This work represents the first effort, to the best of our knowledge, that successfully applies a KD-based framework for image transmission through scattering media. Experimental results demonstrate that even with up to 93.4% reduction in model computational complexity, we can still achieve averaged Structure Similarity Index Measure (SSIM) of 0.76, 0.85, and 0.90 in Fashion-MNIST, EMNIST, and MNIST images respectively, which are very close to the performance of cumbersome teacher models. This work dramatically reduces the complexity of high-fidelity image transmission through MMF and holds broad prospects for applications in resource-constrained environments and hardware implementations.

Neural-network-based carrier-less amplitude phase modulated signal generation and end-to-end optimization for fiber-terahertz integrated communication system.

In fiber-terahertz integrated communication systems, nonlinear distortion and inter-symbol interference (ISI) will degrade transmission performance. Pre-compensation is an efficient method to handle the channel distortion as it can avoid noise boosting during channel compensation and reduce receiver side signal processing algorithmic complexity at user-end (UE) considering the asymmetric access scenario. In this paper, we propose and experimentally demonstrate a neural-network (NN)-based carrier-less amplitude phase (CAP) modulated signal generation and end-to-end optimization method for a fiber-terahertz integrated communication system. The CAP signal is generated directly from quadrature amplitude modulation symbols and pre-compensated through a transmitter NN, which allows the receiver to demodulate the signal with simple linear digital signal process (DSP). In generating the CAP signal, the NN based transmitter learns a group of filters, which can generate, up-convert, and pre-compensate the signals. Based on the proposed method, a fiber-terahertz integration access system at 220 GHz is demonstrated and a sensitivity gain of 1.2 dB is achieved at a transmission speed of 50 Gbps and the forward error correction (FEC) bit error rate (BER) threshold of 1 × 10-2 compared with the baseline after 10-km fiber transmission and 1-m wireless delivering.

113Gbps rainbow visible light laser communication system based on 10λ laser WDM emitting module in fiber-free space-fiber link.

With the advent of the sixth-generation mobile communication standard (6 G), the visible light communication (VLC) technology based on wavelength division multiplexing (WDM) technology can effectively solve the problem of shortage of spectrum resources and insufficient channel capacity. This paper introduces one of our technical achievements, namely the construction of a near-real-time visible light laser communication (VLLC) system based on WDM, which includes a self-designed 10-λ fully-packaged visible light laser emission module, 1 m multimode fiber - 0.175 m free space - 1 m multimode fiber optical transmission link, and receiver array. In the transmitter system, we adopt adaptive discrete multitone (DMT) modulation technique combined with Quadrature Amplitude Modulation (QAM) modulation scheme to obtain maximum spectral efficiency (SE). In the receiving system, we utilize the sparse-structured reservoir computing post-equalization algorithm to achieve superior equalization performance on the basis of the traditional post-equalization algorithm. The experimental results indicate that this quasi-real-time communication system has achieved a signal transmission rate of 113.175Gbps. To the best of our knowledge, this work has set a record in the field of high-speed visible light laser communication. Therefore, the laser communication system constructed by this work, with its flexibility in deployment and high-speed performance, demonstrates the significant potential application of visible light laser communication in data center interconnection and high-speed indoor access networks.

Modulation format recognition in a UVLC system based on an ultra-lightweight model with communication-informed knowledge distillation.

Modulation format recognition (MFR) is a key technology for adaptive optical systems, but it faces significant challenges in underwater visible light communication (UVLC) due to the complex channel environment. Recent advances in deep learning have enabled remarkable achievements in image recognition, owing to the powerful feature extraction of neural networks (NN). However, the high computational complexity of NN limits their practicality in UVLC systems. This paper proposes a communication-informed knowledge distillation (CIKD) method that achieves high-precision and low-latency MFR with an ultra-lightweight student model. The student model consists of only one linear dense layer under a communication-informed auxiliary system and is trained under the guidance of a high-complexity and high-precision teacher model. The MFR task involves eight modulation formats: PAM4, QPSK, 8QAM-CIR, 8QAM-DIA, 16QAM, 16APSK, 32QAM, and 32APSK. Experimental results show that the student model based on CIKD can achieve comparable accuracy to the teacher model. After knowledge transfer, the prediction accuracy of the student model can be increased by up to 87%. Besides, it is worth noting that CIKD's inference accuracy can reach up to 100%. Moreover, the parameters constituting the student model in CIKD correspond to merely 18% of the parameters found in the teacher model, which facilitates the hardware deployment and online data processing of MFR algorithms in UVLC systems.

Net-432-Gb/s/λ PS-PAM transmission based on advanced DSP and single DAC for 400†G/λ IM/DD links.

The escalating surge in datacenter traffic creates a pressing demand for augmenting the capacity of cost-effective intensity modulation and direct detection (IM/DD) systems. In this Letter, we report the demonstration of the single-lane 128-GBaud probabilistically shaped (PS)-PAM-20 IM/DD transmission using only a single digital-to-analog converter (DAC) for a net 400 G/λ system. Based on the advanced digital signal processing (DSP), we achieve net bitrates of up to 437 Gb/s for optical back-to-back and 432 Gb/s after the 0.5-km SSMF transmission in the C-band with 128-Gbaud PS-PAM-20 signals. This work is the latest demonstration on ultra-high-order PS-PAM signals achieving net bitrates exceeding 400 Gb/s despite symbol rate limitations. Notably, to the best of our knowledge, the realized net information rate ([net bitrate]/[symbol rate]) of 3.37 marks a new achievement within the domain of 400 G/λ IM/DD systems, with promising implications for enhancing bandwidth efficiency in the upcoming 1.6-Tb Ethernet scenario.

Wide field-of-view laser-based white light transmitter for visible light communications.

The advancement demands of high-speed wireless data link ask for higher requirements on visible light communication (VLC), where wide coverage stands as a critical criterion. Here, we present the design and implementation of a transmitter structure capable of emitting a high-power wide-coverage white light laser. This laser source exhibits excellent stability, with an irradiation range extending to a half-angle of 20°. Its high brightness satisfies the needs of indoor illumination while maintaining excellent communication performance. Utilizing bit-loading discrete multi-tone modulation, a peak data transmission rate of 3.24 Gbps has been achieved, spanning 1 to 5 m. Remarkably, the data rates exceed 2.5 Gbps within a 40° range at a distance of 5 m, enabling a long-distance, wide coverage, high-speed VLC link for future mobile network applications.

Factors affecting the time interval of endoscopic ultrasound-guided endoscopic necrosectomy of walled-off pancreatic necrosis: A retrospective single-center study in China.

BACKGROUND AND AIM: Endoscopic ultrasound (EUS)-guided endoscopic necrosectomy is an effective and minimally invasive treatment for walled-off pancreatic necrosis (WON). This study investigated the factors affecting the time interval of EUS-guided WON necrosectomy. METHODS: Patients who received EUS-guided necrosectomy in the Endoscopy Center of the First Affiliated Hospital of Chongqing Medical University in the past 5 years were retrospectively analyzed. Data including general information, etiology, blood biochemical indexes, physical signs, CT severity grade, location, size, solid necrotic ratio, type and number of stents, and immediate necrosectomy were collected to explore the relationships between these factors and the interval of endoscopic necrosectomy. RESULTS: A total of 51 WON patients were included. No significant correlation has been noted between the endoscopic debridement interval and the following indexes, including the patients' general information, the etiology of pancreatitis, blood biochemical indexes (leukocyte count, neutrophil percentage, C-reactive protein), preoperative fever, and WON's location and size, type and number of stents, and whether immediate necrosectomy. However, there were significant differences between the debridement interval and the modified CT Severity Index (MCTSI) (p < 0.001), the solid necrotic ratio of WON (p < 0.001) before the intervention, postoperative fever (p = 0.038), C-reactive protein increasing (p = 0.012) and fever before reintervention (p = 0.024). CONCLUSIONS: The EUS-measured solid necrotic ratio, the MCTSI, postoperative fever, C-reactive protein increase, and fever before reintervention in patients affect the time interval of EUS-guided endoscopic necrosectomy in WON patients. These five indicators may be promisingly effective in predicting and managing endoscopic necrosectomy intervals.

Efficacy and Safety of Anhydrous Ethanol-Assisted Endoscopic Ultrasound-Guided Transluminal Necrosectomy in Infected Necrotizing Pancreatitis.

AIM: Endoscopic necrosectomy has become the first-line treatment option for infectious necrotizing pancreatitis (INP), especially walled-off necrosis. However, the problems, including operation-related adverse events (AEs) and the need for multiple endoscopic procedures, have not been effectively addressed. We sought to evaluate the clinical safety and efficacy of anhydrous ethanol-assisted endoscopic ultrasound (EUS)-guided transluminal necrosectomy in INP. METHODS: A single-center observational cohort study of INP patients was conducted in a tertiary endoscopic center. Anhydrous ethanol-assisted EUS-guided transluminal necrosectomy (modified group) and conventional endoscopic necrosectomy (conventional group) were retrospectively compared in INP patients. The technical and clinical success rates, operation time, perioperative AEs, postoperative hospital stay, and recurrent INP rates were analyzed, respectively. RESULTS: A total of 55 patients were enrolled. No statistically significant differences were observed between the two groups regarding baseline characteristics. Compared to patients in the conventional group, patients in the modified group demonstrated significantly reduced times of endoscopic transluminal necrosectomies (1.96 ± 0.89 vs. 2.73 ± 0.98; P = 0.004) and comparable perioperative AEs (P = 0.35). Meanwhile, no statistically significant differences were observed in the technical and clinical success rates (P = 0.92), operation time (P = 0.59), postoperative hospital stay (P = 0.36), and recurrent INP rates (P = 1.00) between the two groups. CONCLUSION: Anhydrous ethanol-assisted EUS-guided transluminal necrosectomy seemed safe and effective in treating INP. Compared with conventional endoscopic transluminal necrosectomy, its advantage was mainly in reducing the number of endoscopic necrosectomies without increasing perioperative AEs.

Laser-Based Mobile Visible Light Communication System.

Mobile visible light communication (VLC) is key for integrating lighting and communication applications in the 6G era, yet there exists a notable gap in experimental research on mobile VLC. In this study, we introduce a mobile VLC system and investigate the impact of mobility speed on communication performance. Leveraging a laser-based light transmitter with a wide coverage, we enable a light fidelity (LiFi) system with a mobile receiving end. The system is capable of supporting distances from 1 m to 4 m without a lens and could maintain a transmission rate of 500 Mbps. The transmission is stable at distances of 1 m and 2 m, but an increase in distance and speed introduces interference to the system, leading to a rise in the Bit Error Rate (BER). The mobile VLC experimental system provides a viable solution to the issue of mobile access in the integration of lighting and communication applications, establishing a solid practical foundation for future research.

Deep-learning-based multi-user framework for end-to-end fiber-MMW communications.

Fiber-wireless integration has been widely studied as a key technology to support radio access networks in sixth-generation wireless communication, empowered by artificial intelligence. In this study, we propose and demonstrate a deep-learning-based end-to-end (E2E) multi-user communication framework for a fiber-mmWave (MMW) integrated system, where artificial neural networks (ANN) are trained and optimized as transmitters, ANN-based channel models (ACM), and receivers. By connecting the computation graphs of multiple transmitters and receivers, we jointly optimize the transmission of multiple users in the E2E framework to support multi-user access in one fiber-MMW channel. To ensure that the framework matches the fiber-MMW channel, we employ a two-step transfer learning technique to train the ACM. In a 46.2 Gbit/s 10-km fiber-MMW transmission experiment, compared with the single-carrier QAM, the E2E framework achieves over 3.5 dB receiver sensitivity gain in the single-user case and 1.5 dB gain in the three-user case under the 7% hard-decision forward error correction threshold.

Spatial pilot-aided fast-adapted framework for stable image transmission over long multi-mode fiber.

Multi-mode fiber (MMF) has emerged as a promising platform for spatial information transmission attributed to its high capacity. However, the scattering characteristic and time-varying nature of MMF pose challenges for long-term stable transmission. In this study, we propose a spatial pilot-aided learning framework for MMF image transmission, which effectively addresses these challenges and maintains accurate performance in practical applications. By inserting a few reference image frames into the transmitting image sequence and leveraging a fast-adapt network training scheme, our framework adaptively accommodates to the physical channel variations and enables online model update for continuous transmission. Experimented on 100 m length unstable MMFs, we demonstrate transmission accuracy exceeding 92% over hours, with pilot frame overhead around 2%. Our fast-adapt learning scheme requires training of less than 2% of network parameters and reduces the computation time by 70% compared to conventional tuning approaches. Additionally, we propose two pilot-insertion strategies and elaborately compare their applicability to a wide range of scenarios including continuous transmission, burst transmission and transmission after fiber re-plugging. The proposed spatial pilot-aided fast-adapt framework opens up the possibility for MMF spatial transmission in practical complicated applications.

11.2 Gbps 100-meter free-space visible light laser communication utilizing bidirectional reservoir computing equalizer.

In this paper, we introduce an innovative post-equalization technique leveraging bidirectional reservoir computing (BiRC), and apply it to waveform-to-symbol level equalization for visible light laser communication for the first time. This strategy is more resistant to nonlinearities compared to traditional equalizers like least mean square (LMS) equalizer, while requiring less training time and fewer parameters than neural network (NN) -based equalizers. Through this approach, we successfully conduct a 100-meter transmission of a 32-amplitude phase shift keying (32APSK) signal using a green laser operating at a wavelength of 520 nm. Remarkably, our system achieves a high data rate of 11.2 Gbps, all while maintaining a satisfying bit error rate (BER) below the 7% hard decision forward error correction (HD-FEC) threshold of 3.8E-3.

High-efficient subwavelength structure engineered grating couplers for 2-µm waveband high-speed data transmission.

The 2-µm waveband is becoming an emerging window for next-generation high-speed optical communication. To enable on-chip high-speed data transmission, improving the signal-to-noise ratio (SNR) by suppressing the coupling loss of a silicon chip is critical. Here, we report grating couplers for TE and TM polarized light at the 2-µm waveband. With a single-step fully etched process on the 340 nm silicon-on-insulator (SOI) platform, the devices experimentally demonstrate high coupling efficiency of -4.0 dB and 1-dB bandwidth of 70 nm for the TE polarized light, while -4.5 dB coupling efficiency and 58 nm 1-dB bandwidth for the TM polarized light. For comprehensive performance, both of them are among the best grating couplers operating in the 2-µm waveband so far. We also demonstrate 81Gbps high-speed on-chip data transmission using pulse amplitude modulation 8-level (PAM-8) signals.

Inverse design of an ultra-compact dual-band wavelength demultiplexing power splitter with detailed analysis of hyperparameters.

Inverse design has been widely studied as an efficient method to reduce footprint and improve performance for integrated silicon photonic (SiP) devices. In this study, we have used inverse design to develop a series of ultra-compact dual-band wavelength demultiplexing power splitters (WDPSs) that can simultaneously perform both wavelength demultiplexing and 1:1 optical power splitting. These WDPSs could facilitate the potential coexistence of dual-band passive optical networks (PONs). The design is performed on a standard silicon-on-insulator (SOI) platform using, what we believe to be, a novel two-step direct binary search (TS-DBS) method and the impact of different hyperparameters related to the physical structure and the optimization algorithm is analyzed in detail. Our inverse-designed WDPS with a minimum feature size of 130 nm achieves a 12.77-times reduction in footprint and a slight increase in performance compared with the forward-designed WDPS. We utilize the optimal combination of hyperparameters to design another WDPS with a minimum feature size reduced to 65 nm, which achieves ultra-low insertion losses of 0.36 dB and 0.37 dB and crosstalk values of -19.91 dB and -17.02 dB at wavelength channels of 1310 nm and 1550 nm, respectively. To the best of our knowledge, the hyperparameters of optimization-based inverse design are systematically discussed for the first time. Our work demonstrates that appropriate setting of hyperparameters greatly improves device performance, throwing light on the manipulation of hyperparameters for future inverse design.

One-bit quantization delta-sigma modulation-based autoencoder for power-efficient free-space communication.

This Letter proposes a novel, to the best of our knowledge, approach utilizing a delta-sigma modulation (DSM)-based 1-bit autoencoder (AE) for efficient encoding and decoding in various channel conditions. Simulation analysis demonstrates the AE's ability to mitigate noise by reducing a peak-to-average power ratio (PAPR) and enhancing an in-band power of the signals, particularly under low signal-to-noise ratios (SNRs). The AE-DSM achieves theoretical transmission performance even at SNRs below 6 dB. In a 40-m free-space link experiment, the AE-DSM exhibits an 8.4-dB lower bit error rate (BER) compared to 64QAM-DSM, enabling a transmission rate of 1.31 Gbps. Furthermore, the 1-bit AE-DSM significantly reduces power consumption in the receiving analog-to-digital converter (ADC), facilitates transmission at low SNRs, and effectively mitigates nonlinear effects. Consequently, the DSM-based AE holds immense potential for future mobile fronthaul links.

8.8 Gbps PAM-4 visible light communication link using an external modulator and a neural network equalizer.

This Letter presents an experimental demonstration of a visible light communication system utilizing a LiNbO3 external modulator to support the transmission of pulse amplitude modulation (PAM)-4 signals. To solve the problem of the low-frequency fluctuations and inter-symbol interference (ISI) introduced by the external modulator-based system, a neural network with a low-frequency signal as the second label (LFNN) is proposed. A data rate of 8.8 Gbps using PAM-4 is experimentally achieved under the 7% hard-decision forward error correction (HD-FEC) bit-error-ratio (BER) limit of 3.8 × 10-3. To the best of our knowledge, this work represents the highest transmission data rate achieved thus far using external modulation in visible light communication systems.

Potential functions and therapeutic implications of glioma-resident mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are emerging crucial regulators in the tumor microenvironment (TME), which contributes to tumor progression and therapeutic resistance. MSCs are considered to be the stromal components of several tumors, their ultimate contribution to tumorigenesis and their potential to drive tumor stem cells, especially in the unique microenvironment of gliomas. Glioma-resident MSCs (GR-MSCs) are non-tumorigenic stromal cells. The phenotype of GR-MSCs is similar to that of prototype bone marrow-MSCs and GR-MSCs enhance the GSCs tumorigenicity via the IL-6/gp130/STAT3 pathway. The higher percentage of GR-MSCs in TME results in the poor prognosis of glioma patients and illuminate the tumor-promoting roles for GR-MSCs by secreting specific miRNA. Furthermore, the GR-MSC subpopulations associated with CD90 expression determine their different functions in glioma progression and CD90low MSCs generate therapeutic resistance by increasing IL-6-mediated FOXS1 expression. Therefore, it is urgent to develop novel therapeutic strategies targeting GR-MSCs for GBM patients. Despite that several functions of GR-MSCs have been confirmed, their immunologic landscapes and deeper mechanisms associated with the functions are not still expounded. In this review, we summarize the progress and potential function of GR-MSCs, as well as highlight their therapeutic implications based on GR-MSCs in GBM patients.

Enhancement of CD70-specific CAR T treatment by IFN-γ released from oHSV-1-infected glioblastoma.

Even with progressive combination treatments, the prognosis of patients with glioblastoma (GBM) remains extremely poor. OV is one of the new promising therapeutic strategies to treat human GBM. OVs stimulate immune cells to release cytokines such as IFN-γ during oncolysis, further improve tumor microenvironment (TME) and enhance therapeutic efficacy. IFN-γ plays vital role in the apoptosis of tumor cells and recruitment of tumor-infiltrating T cells. We hypothesized that oncolytic herpes simplex virus-1 (oHSV-1) enhanced the antitumor efficacy of novel CD70-specific chimeric antigen receptor (CAR) T cells by T cell infiltration and IFN-γ release. In this study, oHSV-1 has the potential to stimulate IFN-γ secretion of tumor cells rather than T cell secretion and lead to an increase of T cell activity, as well as CD70-specific CAR T cells can specifically recognize and kill tumor cells in vitro. Specifically, combinational therapy with CD70-specific CAR T and oHSV-1 promotes tumor degradation by enhancing pro-inflammatory circumstances and reducing anti-inflammatory factors in vitro. More importantly, combined therapy generated potent antitumor efficacy, increased the proportion of T cells and natural killer cells in TME, and reduced regulatory T cells and transformed growth factor-ß1 expression in orthotopic xenotransplanted animal model of GBM. In summary, we reveal that oHSV-1 enhance the therapeutic efficacy of CD70-spefific CAR T cells by intratumoral T cell infiltration and IFN-γ release, supporting the use of CAR T therapy in GBM therapeutic strategies.