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Introduction: Cirrhosis remains a significant clinical challenge due to its poor prognosis and limited treatment options, creating a high unmet medical need for the development of novel therapies. In this study, we analyzed the effects of a novel approach to treat cirrhosis using platelet-rich plasma-derived extracellular vesicles (PRPEV) in mice. Methods: PRPEV were collected from platelet-rich plasma using ultrafiltration, and their proteomes were analyzed. The carbon tetrachloride (CCl4)-induced cirrhosis model of mice was used to evaluate the effect of PRPEV administration and compared with the control group (n = 8). In vitro and in vivo mechanistic analyses of PRPEV administration were confirmed using real time-PCR and immunostaining. Results: Gene ontology analysis based on the proteome revealed that PRPEV contain many factors associated with EV and immune responses. In vitro, PRPEV polarize macrophages into an anti-inflammatory phenotype. Following PRPEV administration, there was a decrease in serum alanine aminotransferase levels and reduction in liver fibrosis, while mRNA levels of regenerative factors were upregulated and transforming growth factor β-1 was downregulated. Furthermore, the number of anti-inflammatory macrophages in the liver increased. Conclusions: PRPEV may contribute to hepatocyte proliferation, anti-inflammation, and anti-fibrogenesis in the liver. This novel concept paves the way for cirrhosis treatment.

Research on the all-photonics metro/access network is active as the next generation communication system. It aims to provide high-throughput, low-latency, low-power-consumption connections via end-to-end optical paths that directly link users without o/e/o conversion. One issue with realizing this network is how to implement the remote-control channel cost-effectively. In this work, we propose a cost-effective control signal transmission system based on auxiliary management and control channel (AMCC) and wavelength division multiplexing (WDM) technology. 25-Gbit/s non-return-to-zero (NRZ) 40 km transmission confirms the feasibility of the proposed system. The experiment comprehensively examines the influence that upstream/downstream control signals and main signals on different paths have on each other's receiver sensitivity. With the appropriate parameters, the penalty on the main signal's receiver sensitivity due to upstream/downstream control signals can be reduced to just 0.5 dB. The proposed method can realize cost-effective control channels in the all-photonics metro/access network with minimal sensitivity degradation.

Developing dedicated hardware for each application in future optical access network systems causes significant initial investment costs. Thus, these costs are alleviated by optical access networks using general-purpose devices related to software-defined networking (SDN) and network function virtualization (NFV). We have studied physical layer virtualization to bring the advantages of SDN and NFV in optical access networks. We have focused on digital coherent technology to enhance capacity and extend reach within optical access networks. However, the future virtualized coherent access faces stringent frequency characteristics and the impact of chromatic dispersion (CD). The number of taps of finite impulse response (FIR) filters in the receiver increases rapidly for the CD compensation. The previously proposed DSP algorithm may not operate in this situation because the processing time exceeds the requirement. Therefore, this paper proposes and implements software for a lightweight multi-input-to-multi-output (MIMO) adaptive equalizer that separates FIR filters depending on the tap update period. The proposed method uses two types of FIR filters; one is used for polarization demultiplexing with short taps, and the other is a filter with long taps for the compensation of the CD in the fiber channel and the frequency distortion from the transceiver. Owing to filter separation, the calculation cost can be reduced. We indicate the processing time meeting desired requirements through real-time transmission experiments, even with increased taps. Additionally, we conduct offline simulations and experiments at a higher symbol rate than the real-time experiment.

Factory networks are typically implemented using dedicated network protocols due to their strict accuracy and latency requirements. However, these protocols tie the factory to specific equipment vendors, making it difficult to introduce other protocols. In response to this challenge, we propose a novel architecture to build a full software-defined factory network by softwarization of industrial Ethernet protocol functions, implementation of a motion control application in a general language, and control of the data plane from the network controller. We demonstrate advanced motion control from a software-defined control system utilizing an industrial Ethernet protocol on a general-purpose server and verify the effectiveness of the proposed architecture. Our proposal makes it possible to control various industrial devices from different vendors without changing applications by mediating the data stored in various protocols through drivers for each protocol. Our experimental findings demonstrate that the PROFINET software-based motion control system can be successfully implemented. The results also show that the proposed architecture can achieve successful motor control within 11.5 s by utilizing the delay compensation method.

With the evolution of access systems by network function virtualization (NFV) and the software-defined network (SDN), further softwarization including transmission functions is required in order to fully utilize the advantages that softwarization offers to network operators in terms of more flexible and rapid service creation and migration. The softwarization of digital signal processing (DSP) is a prime target, but frequency offset compensation (FOC) has serial processing, which makes its softwarization difficult. In particular, the pre-decision-based angle differential estimator (PADE) of wide-range FOC needs long serial iterations since it obtains stable solutions by using small loop gain in the loop filter. This paper proposes a multiplication-based FOC implementation and a novel multi-thread PADE algorithm for real-time softwarization. The multiplication-based implementation enables parallel compensation of phase rotation by multiplying the estimated CFOs by sampling numbers for Viterbi-and-Viterbi (VV) method and PADE. In addition, our multi-thread PADE algorithm significantly reduces the iterations needed for FOC estimation; using multi-threading, it estimates multiple frequency offsets using the loop filters with large loop gain. This calculation needs relatively few iterations, but its outputs are very noisy, and final frequency offset estimates are obtained after removing the noise by clustering and averaging the results. The results of simulations and experiments, which use a general-purpose server with a graphic processing unit, show that our PADE algorithm is 1,308 times faster than the conventional implementation and 5-Gb/s real-time processing is achieved while maintaining the FOC performance.

Beyond 5th generation (5G) and 6th generation (6G) mobile systems require not only low latency but also low jitter for deterministic services such as remote operation. Since remote operation requires high-definition video streaming in the uplink, the uplink transmission performance will become more important. However, current new radio (NR) mobile systems cause jitter in the uplink traffic of the mobile backhaul (MBH) network because of the radio transmission schemes such as downlink/uplink separation of time division duplexing (TDD) and medium access control (MAC) service data unit (SDU) concatenation to compose transport blocks. Thus, we propose MBH uplink jitter reduction techniques with optical-wireless cooperative control. Our proposed techniques execute traffic shaping at a router in the MBH network to reduce uplink jitter. The shaping rate that reduces jitter while minimizing latency increase is calculated with mobile scheduling information forwarded from a next generation node B (gNB) via an extended cooperative transport interface (eCTI). The eCTI provides an interface between gNBs and network equipment to achieve optical-wireless cooperative control. In this paper, we experimentally validate our proposed jitter reduction techniques through a combination of simulations for radio transmission and experiments with a shaper prototype we developed. The results regarding end-to-end (E2E) jitter performance indicate that the proposed techniques reduce the maximum jitter by 88%, from 1.1 ms to $137 ~\mu \text{s}$ .

The All-Photonics Metro-Access Converged Network (APN) aims to achieve a flat and simple architecture that even covers access areas and represents the evolution of optical transport. Electrical processing functions such as exchange, multiplexing, and switching are uniformly placed at the border of the network segments, i.e., access, metro, and core networks, in current optical networks. These functions are placed in Data Centric Infrastructure (DCI) and accessed only when needed in the APN. By flexibly providing direct optical connections between user premises and/or DCI according to requests from users and services, the APN creates new types of use cases requiring end-to-end guaranteed wide-bandwidth and/or extremely low latency and jitter along with an information-computing platform. To provide optical paths originating from user terminals that launch client signals using protocols preferable to their applications, we propose a configuration for a novel optical edge node, the Photonic Gateway (GW), and a procedure based on remote control of user terminals to establish end-to-end optical paths that are independent of the client signal protocol. To verify these, we present results of a proof-of-concept experimental demonstration of establishing end-to-end optical paths. An auxiliary management control channel is employed in the protocol-independent access control method. We also describe future challenges facing the Photonic GW that must be addressed.

The burst-mode continuous phase frequency shift-keying (CPFSK) transmitter that combines a directly modulated laser diode, an electro absorption modulator and a semiconductor optical amplifier is attractive as a cost-effective transmitter for phase modulation formats for digital signal processing (DSP)-based coherent passive optical network (PON) upstream signaling. However, since highly accurate wavelength controllers for the transmitters in optical network units (ONUs) create excessive cost burdens, large carrier frequency offsets (CFOs) must be expected. Thus, a CFO compensation method with wide compensation range is required. This paper proposes a novel CFO estimation and compensation method for burst-mode CPFSK signals in upstream PON signaling. The proposed method is based on a simple blind algorithm and does not require any training symbols. We demonstrate wide CFO compensation range, from −12 to 14 GHz, with high receiver sensitivity, less than −42.5 dBm for 10 Gbit/s binary CPFSK signals. This range far exceeds that of the conventional CFO compensation method using a blind algorithm. Moreover, the proposed method can enhance the convergence of finite impulse response (FIR) filters. The feasibility of the proposed CFO compensation technique is successfully demonstrated for burst-mode CPFSK signals.

In the remote motion control of IoT devices, the delay adversely affects control performance. In our access edge concept, in which motion control is performed from a central office, the delay becomes large due to Dynamic Bandwidth Allocation (DBA) when the Passive Optical Network (PON) is adopted as the access system. No existing motion control method considers the delay changes of the DBA algorithm. We rectify this omission by proposing a novel real-time and high-precision motion control method that links the PON device and the controller. The proposed method can improve the control performance while maintaining the bandwidth utilization efficiency without changing the DBA delay specified to meet the requirements. In the proposed method, the delay in the PON system is calculated by using a delay model based on the setting parameter received from the communication device, and is used for delay compensation control. An experiment shows that, unlike the conventional method which becomes unstable and fails to realize control, the proposed method achieves high resolution control within 4 s, which demonstrates the feasibility of motion control for factory automation using edge computing in PON systems.

Abstract Mesenchymal stromal cells (MSCs) are used for ameliorating liver fibrosis and aiding liver regeneration after cirrhosis; Here, we analyzed the therapeutic potential of small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs). γ-sEVs effectively induced anti-inflammatory macrophages with high motility and phagocytic abilities in vitro, while not preventing hepatic stellate cell (HSC; the major source of collagen fiber) activation in vitro. The proteome analysis of MSC-derived sEVs revealed anti-inflammatory macrophage inducible proteins (e.g., annexin-A1, lactotransferrin, and aminopeptidase N) upon IFN-γ stimulation. Furthermore, by enabling CX3CR1+ macrophage accumulation in the damaged area, γ-sEVs ameliorated inflammation and fibrosis in the cirrhosis mouse model more effectively than sEVs. Single cell RNA-Seq analysis revealed diverse effects, such as induction of anti-inflammatory macrophages and regulatory T cells, in the cirrhotic liver after γ-sEV administration. Overall, IFN-γ pre-conditioning altered sEVs resulted in efficient tissue repair indicating a new therapeutic strategy.

Abstract Objectives Diversion colitis (DC) is an inflammatory disorder caused by interruption of the fecal stream and subsequent nutrient deficiency from luminal bacteria. The utility of fecal microbiota transplantation (FMT) for DC was recently investigated; however, the precise pathogenesis of this condition remains unclear. This study aimed to evaluate the utility of autologous FMT in DC and to determine the related changes in the intestinal microbiota. Methods Autologous FMT was performed to reestablish the intestinal microbiota in five patients (average age, 64.6 ± 8.3 years) with DC. They underwent double‐ended colostomy. We assessed the diverted colon by endoscopy and evaluated the microbiota before and after FMT using the 16S rRNA gene sequencing method. Results All five patients had mild inflammation (ulcerative colitis endoscopic index of severity [UCEIS] 2–3) in the diverted colon based on the colonoscopic findings. Three patients presented with symptoms, such as tenesmus, mucoid stool, and bloody stool. With FMT treatment, all patients achieved endoscopic remission (UCEIS score of 0 or 1) and symptomatic improvement. We observed a significantly decreased α‐diversity in DC patients compared to healthy controls. The frequency of aerobic bacteria, such as Enterobacteriaceae, in the diverted colon decreased after autologous FMT. Conclusions This study was the first to show that the microbiota in the diverted colon was significantly affected by autologous FMT. Since interruption of the fecal stream is central to the development of DC, FMT can be considered a promising treatment.

Introduction: Currently, there are no approved drugs for treating non-alcoholic steatohepatitis (NASH); however, mesenchymal stem cells (MSCs) and their small extracellular vesicles (sEVs), which possess immunomodulatory activities, are potential candidates. This study aimed to develop a mouse model of NASH with rapid accumulation of fibrosis using the pre-established melanocortin type-4 receptor knockout (Mc4r-KO) NASH mouse model and lipopolysaccharide (LPS), and to evaluate the therapeutic effect of MSCs and their sEVs. Methods: Mc4r-KO mice (8 weeks old, male) were fed a western diet (WD) for 8 weeks. Next, the mice were intraperitoneally injected with lipopolysaccharide (LPS) twice a week for 4 weeks while continuing the WD. To confirm the therapeutic effect of MSCs and sEVs, human adipose tissue-derived MSCs or their sEVs were administered 12 weeks after initiation of the WD, and serum testing, quantitative analysis of fibrosis, and quantitative reverse transcription-polymerase chain reaction qRT-PCR were performed. Results: By providing a WD combined with LPS treatment, we successfully developed a NASH model with rapid accumulation of fibrosis. Both human MSCs and their sEVs decreased serum alanine transaminase levels and inflammatory markers based on qRT-PCR. Histological analysis showed that MSC or sEV treatment did not affect fat accumulation. However, an improvement in fibrosis in the groups treated with MSCs and their sEVs was observed. Furthermore, after administering MSCs and sEVs, there was a significant increase in anti-inflammatory macrophages in the liver. Conclusion: We successfully developed a NASH model with rapid accumulation of fibrosis and confirmed the anti-inflammatory and anti-fibrotic effects of MSCs and their sEVs, which may be options for future therapy.

Abstract Mesenchymal stem cells (MSCs) can be cultured relatively easily and can be obtained not only from the bone marrow, but also from medical waste such as adipose tissue and umbilical cord tissue. Because of its low antigenicity, allogeneic MSC injection is safe. MSCs have been evaluated in more than 900 clinical trials in a variety of fields, with more than 50 clinical trials related to liver diseases. Experiments have suggested that MSCs function as “conducting cells” to affect various “effective cells” such as T cells, B cells, and macrophages. Recent clinical trials have focused on allogeneic MSCs. Thus, studies are needed to determine the most effective cell source, culture conditions, cell numbers, administration frequency, administration route, cost, safety, and liver disease treatments. Recently, the functions of exosomes have gained attention, and cell-free therapy may become possible as an alternative therapy for liver disease. In this review, we introduce general information, mechanism, representative clinical study data, recently started or planned clinical trials, and possibility of cell-free therapy of MSCs.