Multiple-signal-joint-processing-based guard interval shortening method for a CS-NFDM system.

Aiming to further improve the spectral efficiency (SE) of a continuous spectrum modulated nonlinear frequency division multiplexing (CS-NFDM) system, we propose a novel ,to the best of our knowledge, multiple-signal-joint-processing (MSJP)-based guard interval (GI) shortening method. In this method, multiple NFDM time-domain signals are jointly processed as a whole to carry out nonlinear Fourier transform and inverse nonlinear Fourier transform (NFT-INFT) operations. These operations can fuse the multiple NFDM time-domain signals together, which is equivalent to the corresponding inverse process of a fiber transmission. Experimental results show that the normalized SE of the proposed method can reach 0.99 when approaching the limit value of 1 and obtain a 2.33 dB Q2-factor improvement compared with the pre-dispersion compensation (PDC) method under the same GI of 0.03 ns in an 80 km SSMF transmission of a 46 GHz signal bandwidth. Furthermore, in comparison with the PDC method, the proposed method can achieve 32.86% normalized SE improvement in the 1120 km SSMF transmission of 32 GHz signal bandwidth under the SD-FEC of 2.4E-2.

Distinct Thalamo-Subcortical Circuits Underlie Painful Behavior and Depression-Like Behavior Following Nerve Injury.

Clinically, chronic pain and depression often coexist in multiple diseases and reciprocally reinforce each other, which greatly escalates the difficulty of treatment. The neural circuit mechanism underlying the chronic pain/depression comorbidity remains unclear. The present study reports that two distinct subregions in the paraventricular thalamus (PVT) play different roles in this pathological process. In the first subregion PVT posterior (PVP), glutamatergic neurons (PVPGlu) send signals to GABAergic neurons (VLPAGGABA) in the ventrolateral periaqueductal gray (VLPAG), which mediates painful behavior in comorbidity. Meanwhile, in another subregion PVT anterior (PVA), glutamatergic neurons (PVAGlu) send signals to the nucleus accumbens D1-positive neurons and D2-positive neurons (NAcD1→D2), which is involved in depression-like behavior in comorbidity. This study demonstrates that the distinct thalamo-subcortical circuits PVPGlu→VLPAGGABA and PVAGlu→NAcD1→D2 mediated painful behavior and depression-like behavior following spared nerve injury (SNI), respectively, which provides the circuit-based potential targets for preventing and treating comorbidity.

A moderately higher time-in-range threshold improves the prognosis of type 2 diabetes patients complicated with COVID-19.

Objective: After fully lifting coronavirus disease 2019 (COVID-19) pandemic control measures in mainland China in 12/2022, the incidence of COVID-19 has increased markedly, making it difficult to meet the general time-in-range (TIR) requirement. We investigated a more clinically practical TIR threshold and examined its association with the prognosis of COVID-19 patients with type 2 diabetes(T2D). Research design and methods: 63 T2D patients complicated with COVID-19 were evaluated. Patients were divided into favorable outcome group and adverse outcome group according to whether achieving composite endpoint (a >20-day length of stay, intensive care unit admission, mechanical ventilation use, or death). TIR, the time-below-range (TBR) and the time-above-range (TAR) were calculated from intermittently scanned continuous glucose monitoring. Logistic regression analysis and other statistical methods were used to analyze the correlation between glucose variability and prognosis to establish the appropriate reference range of TIR. Results: TIR with thresholds of 80 to 190 mg/dL was significantly associated with favorable outcomes. An increase of 1% in TIR is connected with a reduction of 3.70% in the risk of adverse outcomes. The Youden index was highest when the TIR was 54.73%, and the sensitivity and specificity were 58.30% and 77.80%, respectively. After accounting for confounding variables, our analysis revealed that threshold target ranges (TARs) ranging from 200 mg/dL to 230 mg/dL significantly augmented the likelihood of adverse outcomes. Conclusion: The TIR threshold of 80 to 190 mg/dL has a comparatively high predictive value of the prognosis of COVID-19. TIR >54.73% was associated with a decreased risk of adverse outcomes. These findings provide clinically critical insights into possible avenues to improve outcomes for COVID-19 patients with T2D.

A customizable and defined medium supporting culturing of Candida albicans, Staphylococcus aureus, and human oral epithelial cells.

Candida albicans, an opportunistic oral pathogen, synergizes with Staphylococcus aureus, allowing bacteria to co-invade and systemically disseminate within the host. Studying human-microbe interactions creates the need for a universal culture medium that supports fungal, bacterial, and human cell culturing, while allowing sensitive analytical approaches such as OMICs and chromatography techniques. In this study, we established a fully defined, customizable adaptation of Dulbecco's modified Eagle medium (DMEM), allowing multi-kingdom culturing of S. aureus, C. albicans, and human oral cell lines, whereas minimal version of DMEM (mDMEM) did not support growth of S. aureus, and neither did supplementation with dextrose, MEM non-essential amino acids, pyruvate, and Glutamax. This new medium composition, designated as "mDMEM-DMP," promoted growth of all tested S. aureus strains. Addition of 25 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) further improved growth, while higher concentrations did not improve growth any further. Higher concentrations of HEPES did result in prolonged stabilization of medium pH. mDMEM-DMP promoted (hyphal) C. albicans monoculturing and co-culturing on both solid and semi-solid surfaces. In contrast to S. aureus, addition of HEPES reduced C. albicans maximum culture optical density (OD). Finally, only buffered mDMEM-DMP (100 mM HEPES) was successful in maintaining the metabolic activity of human oral Ca9-22 and HO1N1 cell lines for 24 hours. Altogether, our findings show that mDMEM-DMP is a versatile and potent culture medium for both microbial and human cell culturing, providing a customizable platform to study human as well as microbial molecular physiology and putative interactions. IMPORTANCE: Interaction between microbes and the host are in the center of interest both in disease and in health. In order to study the interactions between microbes of different kingdoms and the host, alternative media are required. Synthetic media are useful as they allow addition of specific components. In addition, well-defined media are required if high-resolution analyses such as metabolomics and proteomics are desired. We describe the development of a synthetic medium to study the interactions between C. albicans, S. aureus, and human oral epithelial cells. Our findings show that mDMEM-DMP is a versatile and potent culture medium for both microbial and human cell culturing, providing a customizable platform to study human as well as microbial molecular physiology and putative interactions.

Pure Water Splitting Driven by Overlapping Electric Double Layers.

In pursuit of a sustainable future powered by renewable energy, hydrogen production through water splitting should achieve high energy efficiency with economical materials. Here, we present a nanofluidic electrolyzer that leverages overlapping cathode and anode electric double layers (EDLs) to drive the splitting of pure water. Convective flow is introduced between the nanogap electrodes to suppress the crossover of generated gases. The strong electric field within the overlapping EDLs enhances ion migration and facilitates the dissociation of water molecules. Acidic and basic environments, which are created in situ at the cathode and anode, respectively, enable the use of nonprecious metal catalysts. All these merits allow the reactor to exhibit a current density of 2.8 A·cm-2 at 1.7 V with a nickel anode. This paves the way toward a new type of water electrolyzer that needs no membrane, no supporting electrolyte, and no precious metal catalysts.

Joint signal-to-signal beat interference mitigation for the field recovery of symmetric carrier-assisted differential detection with low carrier-to-signal power ratio.

As a combination of direct detection and coherent detection technologies, self-coherent detection has the advantages of low cost and optical field recovery ability. However, most of the self-coherent detection techniques are limited to single sideband (SSB) signals. Recently, carrier-assisted differential detection (CADD) has been proposed to realize complex-valued double sideband (DSB) signals, but it requires a high carrier-to-signal power ratio (CSPR) to mitigate the signal-to-signal beat interference (SSBI). Later, a more cost-effective symmetric CADD (S-CADD) has been proposed while the required CSPR is still high. In order to alleviate the high requirements of CSPR, we propose a scheme based on the joint of digital pre-distortion (DPD) at transmitter and clipping at receiver to further improve the S-CADD system performance. This joint processing can not only solve the problem of non-uniform distribution of subcarrier signal-to-noise ratio (SNR) caused by non-ideal transfer function, but also the error propagation problem caused by enhanced SSBI under low CSPR. After the validation of the 64 Gbaud 16-ary quadrature amplitude modulation (16-QAM) orthogonal frequency division multiplexing (OFDM) signal transmitted over 80 km standard single mode fiber (SSMF), the CSPR required by the proposed scheme to reach the 20% soft decision-forward error correction (SD-FEC) and 7% hard decision-forward error correction (HD-FEC) can be reduced by 1.3 dB and 2.8 dB, respectively, with a comparison of the conventional S-CADD. The results show the potential of the proposed scheme in the short-reach optical transmissions.

Single wavelength MDM-PDM 800-Gb/s net data rate transmission over a standard multimode fiber employing a Kramers-Kronig receiver.

We propose a high-speed multimode fiber short-reach optical interconnect system based on a Kramers-Kronig (KK) field reconstruction with the mode division multiplexing (MDM) and polarization division multiplexing (PDM) technology. In this work, the LP01, LP21a, LP21b, and LP02 modes are selected as independent channels to carry information. The demonstration achieved the 800 Gb/s net data rate per wavelength with a bit-rate-distance-product (BDP) of 8 Tb/s·km. To the best of our knowledge, this is the highest experimental record of a single wavelength BDP over the SMMF with KK detection. In addition, we discuss the system performance after all multiple-input multiple-output (MIMO) and partial MIMO processing and give guidance on the trade-off between system performance and computational resource.

V-Doped CoSe2 Nanowire Catalysts in a 3D-Structured Electrode for Durable Li-S Pouch Cells.

Lithium-sulfur (Li-S) batteries have high theoretical energy density and are regarded as a promising candidate for next-generation energy storage systems. However, their practical applications are hindered by the slow kinetics of sulfur conversion and polysulfide shuttling. In particular, large-scale pouch cells show much poor cyclability. Here, we develop a high-efficiency catalyst of V-doped CoSe2 by studying the binary CoSe2-VSe2 system and confirming its effectiveness in accelerating polysulfide conversion. The coin cell tests reveal an initial capacity of 1414 mAh g-1 at 0.1 C and 1049 mAh g-1 at 1 C and demonstrate 1000 times cyclability with a decaying rate of 0.05% per cycle. Furthermore, the assembly and construction of pouch cells were optimized with monolithic three-dimensional (3D) electrodes and a multistacking strategy. Specifically, a 3D metallic scaffold (3MS) was developed to host V-doped CoSe2 nanowires and sulfur. In addition, Janus microspheres of C@TiO2 were synthesized to capture polar polysulfides with their polar part of TiO2 and adsorb nonpolar sulfur with their nonpolar part of carbon. By integrating with 3MS, C@TiO2 microspheres can block all ion channels of 3MS and only allow Li ions in and out. These integral designs and monolithic structures enable multistacking pouch cells with high cyclability. A high-loading pouch cell was demonstrated with a total capacity of 700 mAh. The cell can be cycled for 70 times with a capacity retention of 65.7%. In brief, this work provides an integral strategy of catalyst design and overall 3D assembly for practical Li-S batteries in a large pouch cell format.

Experimental demonstration of optical waveform transmission with multiple-eigenvalue 16-APSK modulation.

The multi-eigenvalue multiplexing-based discrete spectrum-modulated nonlinear frequency-division multiplexing (DS-NFDM) system with higher-order modulation format has been demonstrated experimentally. After designing the coefficients of the eigenvalue set and the constellation point distribution of 16-amplitude phase shift keying (16-APSK), the realizations of 14-, 30-, and 46-eigenvalue multiplexed DS-NFDM signals have been implemented. The results show that 46-eigenvalue and 30-eigenvalue multiplexed DS-NFDM signals can transmit 50 km and 400 km over a nonzero dispersion-shifted fiber (NZDSF) under soft-decision forward error correction (SD-FEC) threshold of 2.4E-2, respectively. This demonstration shows for the first time, to the best of our knowledge, the record for multiplexed eigenvalue number and data rate of the multiple-eigenvalue-based DS-NFDM system.

Overexpression of GPX2 gene regulates the development of porcine preadipocytes and skeletal muscle cells through MAPK signaling pathway.

Glutathione peroxidase 2 (GPX2) is a selenium-dependent enzyme and protects cells against oxidative damage. Recently, GPX2 has been identified as a candidate gene for backfat and feed efficiency in pigs. However, it is unclear whether GPX2 regulates the development of porcine preadipocytes and skeletal muscle cells. In this study, adenoviral gene transfer was used to overexpress GPX2. Our findings suggest that overexpression of GPX2 gene inhibited proliferation of porcine preadipocytes. And the process is accompanied by the reduction of the p-p38. GPX2 inhibited adipogenic differentiation and promoted lipid degradation, while ERK1/2 was reduced and p-p38 was increased. Proliferation of porcine skeletal muscle cells was induced after GPX2 overexpression, was accompanied by activation in JNK, ERK1/2, and p-p38. Overexpression methods confirmed that GPX2 has a promoting function in myoblastic differentiation. ERK1/2 pathway was activated and p38 was suppressed during the process. This study lays a foundation for the functional study of GPX2 and provides theoretical support for promoting subcutaneous fat reduction and muscle growth.

Toxicological evaluation and preliminary exposure assessment on glycerol monocaprylate.

As a commonly used food preservative, glycerol monocaprylate (GMC) has limited information and lacked a comprehensive risk assessment. In this study, we conducted in vitro genotoxicity tests, a 90-day subchronic toxicity study, and dietary exposure assessment in China. Rats (n = 10/sex/group) were orally administered GMC at doses of 1.02, 2.04, and 4.08 g/kg BW/day along with a water and corn oil for 90 days, including satellite groups (n = 5/sex/group) in the control groups and 4.08 g/kg BW dose group for observation after 90 days. Body weight, food consumption, hematology, serum biochemistry, urinalysis, endocrine hormone level and other metrics were examined. GMC did not exhibit genotoxicity based on the genotoxicity tests results, and an acceptable daily intake (ADI) of 40.8 mg/kg BW/day was established based on the 90-day subchronic toxicity study. Estimated daily intake of GMC for general population and consumer population in China were 0.99 mg/kg BW/day and 3.19 mg/kg BW/day respectively, which were significantly lower than the ADI. Our findings suggest that GMC does not pose a known health risk to Chinese consumers at the current usage level.

A state feedback control with compensation for permanent magnet synchronous machine drives.

Using the linear approach to design a controller is still prevalent. The state feedback control (SFC) is applied in this paper to improve the dynamic response of permanent magnet synchronous machine (PMSM) speed regulation systems. First, a third-order augmented system is constructed for the reason that a higher-order system has better disturbance rejection. It can be found through analysis and comparison that the order of the proposed speed controller is increased. The parameters of SFC are selected by utilizing the linear quadratic regulator (LQR), and the influence of matrix Q on dynamic performance is detailed through the Bode diagram. Additionally, considering parametric uncertainties and unmodeled dynamics, a disturbance observer (DOB) using the Luenberger observer is designed to further boost anti-disturbance performance. Finally, plenty of experimental results verify the effectiveness of the proposed methods.

Characterization of a group of germacrene A synthases involved in the biosynthesis of ß-elemene from Atractylodis macrocephala.

ß-Elemene, an important component of the volatile oil of Atractylodis macrocephala, has been widely utilized as an antitumor drug for over 20 years. However, the germacrene A synthase (GAS) genes responsible for the biosynthesis of ß-elemene in A. macrocephala were previously unidentified. In this study, two new AmGASs were identified from the A. macrocephala transcriptome, demonstrating their capability to convert farnesyl pyrophosphate into germacrene A, which subsequently synthesizes ß-elemene through Cope rearrangement. Additionally, two highly catalytic AmGAS1 mutations, I307A and E392A, resulted in a 2.23-fold and 1.57-fold increase in ß-elemene synthesis, respectively. Furthermore, precursor supply and fed-batch strategies were employed to enhance the precursor supply, resulting in ß-elemene yields of 7.3 mg/L and 33.3 mg/L, respectively. These findings identify a promising candidate GAS for ß-elemene biosynthesis and lay the foundation for further functional studies on terpene synthases in A. macrocephala.

Modified whitehead hemorrhoidectomy versus partial hemorrhoidectomy for fourth-degree circular mixed hemorrhoids: A retrospective analysis.

Background: Grade IV circular hemorrhoids are difficult to treat. We aim to describe the modified whitehead hemorrhoidectomy procedure and to assess the effectiveness and safety of this procedure for grade IV circular hemorrhoid patients. Methods: Patients with grade Ⅳ circular hemorrhoids who underwent modified Whitehead hemorrhoidectomy and partial hemorrhoidectomy for fourth-degree circular mixed hemorrhoids were retrospectively reviewed. Clinical data were extracted from the database at our institution, and long-term postoperative complications were assessed through repeated outpatient examinations and telephonic communication. Results: A total of 205 patients were included in this study. The mean operative time was 59.2 ± 13.8 min. The average hospital stay was 4.6 ± 1.0 days. For postoperative complications, 66 (32.2%) patients had urinary retention, 10 (4.9%) patients had a sense of incomplete rectal emptying, 5 (2.4%) patients had anal incontinence, and 6 (2.9%) patients had wound infection. For long-term postoperative complications, 3 (1.5%) patients experienced mild to moderate anal stricture, 2 (1%) patients experienced mucosal ectropion, they all had smooth recoveries, and none of them needed secondary surgery. None of these patients had a hemorrhoid recurrence. A total of 205 patients who received modified Whitehead hemorrhoidectomy and 161 who received partial hemorrhoidectomy were included. There were no residual hemorrhoids in patients who received modified Whitehead hemorrhoidectomy, and none had hemorrhoid recurrence. Fifty-eight patients who received partial hemorrhoidectomy had hemorrhoidal residues, and 19 patients experienced hemorrhoid recurrence. After modified Whitehead hemorrhoidectomy, 3 patients developed anal stenosis, and 2 had mucosal ectropion. Four patients developed anal stricture after partial hemorrhoidectomy, and none had mucosal ectropion. They all had smooth recoveries, and none of them needed a secondary surgery. For the mean duration of surgery, postoperative bleeding, postoperative pain, wound infection, sense of incomplete rectal emptying, anal incontinence, and urinary retention, no statistically significant differences were found between the two groups. Conclusions: Compared with partial hemorrhoidectomy, modified whitehead hemorrhoidectomy is an effective and safe surgical procedure and does not significantly increase the risk of anal stenosis and mucosal ectropion for grade IV circular hemorrhoid patients. Prospective randomized controlled trials are needed to verify our results.

Proposals for gas-detection improvement of the FeMPc monolayer towards ethylene and formaldehyde by using bimetallic synergy.

Development and fabrication of a novel gas sensor with superb performance are crucial for enabling real-time monitoring of ethylene (C2H4) and formaldehyde (H2CO) emissions from industrial manufacture. Herein, first-principles calculations and AIMD simulations were carried out to investigate the effect of the Fe-M dimer on the adsorption of C2H4 and H2CO on metal dimer phthalocyanine (FeMPc, M = Ti-Zn) monolayers, and the electronic structures and sensing properties of the above adsorption systems were systematically discussed. The results show that the FeMPc (M = Ti, V, Cr, Mn) monolayers interact with C2H4 and H2CO by chemisorption except for the FeMnPc/H2CO system, while the other adsorption systems are all characterized by physisorption. Interestingly, the adsorption strength of C2H4 and H2CO can be effectively regulated by the bimetallic synergy of the Fe-M dimer. Moreover, the FeCrPc and FeMnPc monolayers exhibit excellent sensitivity towards C2H4 and H2CO, and have short recovery time (4.69 ms-2.31 s) for these gases at room temperature due to the effective surface diffusion at 300 K. Consequently, the FeCrPc and FeMnPc materials can be utilized as high-performance, reusable gas sensors for detecting C2H4 and H2CO, and have promising applications in monitoring the release of ethylene and formaldehyde from industrial processes.

Distribution, occurrence, and leachability of typical heavy metals in coal gasification slag.

Coal gasification slag (CGS) contains variable amounts of heavy metals, which can negatively impact the environment. The mineral composition, element distribution, occurrence, and leaching characteristics of heavy metals in coal gasification coarse slag (CGCS) and coal gasification fine slag (CGFS) are studied to explain the leaching behavior of heavy metals in CGS. The movable components of heavy metals in CGFS (0.06 %-63.03 %) are significantly higher than those in CGCS (0 %-18.72 %). Leaching Environmental Assessment Framework 1313 data shows that heavy metals Zn, Cr, Cd, As, Pb, Ni, and Cu exhibit high leaching rates at low pH conditions, with Zn leaching concentrations as high as 2.11 mg/L at pH 2. Zn, Cr, and As exhibit obvious amphoteric leaching characteristics, and the leaching concentration of As at high pH (1.34 mg/L) even exceeds that at low pH (1.31 mg/L). Except for Cu, all heavy metals in CGS exceed the class III groundwater standard in some cases. Therefore, evaluation is needed before resource utilization of CGS due to potential leaching of some heavy metals.

Mechanistic Approach Toward the C4-Selective Amination of Pyridines via Nucleophilic Substitution of Hydrogen.

The development of site-selective functionalization of N-heteroarenes is highly desirable in streamlined synthesis. In this context, direct amination of pyridines stands as an important synthetic methodology, with particular emphasis on accessing 4-aminopyridines, a versatile pharmacophore in medicinal chemistry. Herein, we report a reaction manifold for the C4-selective amination of pyridines by employing nucleophilic substitution of hydrogen (SNH). Through 4-pyridyl pyridinium salt intermediates, 4-aminopyridine products are obtained in reaction with aqueous ammonia without intermediate isolation. The notable regioselectivity was achieved by the electronic tuning of the external pyridine reagents along with the maximization of polarizability in the proton elimination stage. Further mechanistic investigations provided a guiding principle for the selective C-H pyridination of additional N-heteroarenes, presenting a strategic avenue for installation of diverse functional groups.

Mechanisms of Action of Potentilla discolor Bunge in Type 2 Diabetes Mellitus Based on Network Pharmacology and Experimental Verification in Drosophila.

Purpose: Type 2 diabetes mellitus (T2DM) is associated with reduced insulin uptake and glucose metabolic capacity. Potentilla discolor Bunge (PDB) has been used to treat T2DM; however, the fundamental biological mechanisms remain unclear. This study aimed to understand the active ingredients, potential targets, and underlying mechanisms through which PDB treats T2DM. Methods: Components and action targets were predicted using network pharmacology and molecular docking analyses. PDB extracts were prepared and validated through pharmacological intervention in a Cg>InRK1409A diabetes Drosophila model. Network pharmacology and molecular docking analyses were used to identify the key components and core targets of PDB in the treatment of T2DM, which were subsequently verified in animal experiments. Results: Network pharmacology analysis revealed five effective compounds made up of 107 T2DM-related therapeutic targets and seven protein-protein interaction network core molecules. Molecular docking results showed that quercetin has a strong preference for interleukin-1 beta (IL1B), IL6, RAC-alpha serine/threonine-protein kinase 1 (AKT1), and cellular tumor antigen p53; kaempferol exhibited superior binding to tumor necrosis factor and AKT1; ß-sitosterol demonstrated pronounced binding to Caspase-3 (CASP3). High-performance liquid chromatography data quantified quercetin, kaempferol, and ß-sitosterol at proportions of 0.030%, 0.025%, and 0.076%, respectively. The animal experiments revealed that PDB had no effect on the development, viability, or fertility of Drosophila and it ameliorated glycolipid metabolism disorders in the diabetes Cg>InRK1409A fly. Furthermore, PDB improved the body size and weight of Drosophila, suggesting its potential to alleviate insulin resistance. Moreover, PDB improved Akt phosphorylation and suppressed CASP3 activity to improve insulin resistance in Drosophila with T2DM. Conclusion: Our findings suggest that PDB ameliorates diabetes metabolism disorders in the fly model by enhancing Akt activity and suppressing CASP3 expression. This will facilitate the development of key drug targets and a potential therapeutic strategy for the clinical treatment of T2DM and related metabolic diseases.

The development history, current state, challenges, and future directions of the BASIC-OHCA registry in China: A narrative review.

Out-of-hospital cardiac arrest is a major public health problem worldwide due to its high burden and poor outcomes. Despite progress in treatment, patient outcomes remain unsatisfactory, particularly in low-resource settings. The establishment of a registry is the first step towards gaining a comprehensive understanding of prevailing local conditions and identifying potential opportunities for improving patient survival. Here, we provide a narrative review of the BASeline Investigation of Out-of-hospital Cardiac Arrest (BASIC-OHCA), the first national OHCA registry in China, to introduce its development history, current state, challenges and future directions. We aim to enhance cross-cultural understanding by providing insights from China, while also serving as a reference for the implementation of large-scale registries in low-resource settings.

An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii.

Crosstalk of microbes with human gut epithelia and immune cells is crucial for gut health. However, there is no existing system for a long-term co-culture of human innate immune cells with epithelium and oxygen-intolerant commensal microbes, hindering the understanding of microbe-immune interactions in a controlled manner. Here, we established a gut epithelium-microbe-immune (GuMI) microphysiological system to maintain the long-term continuous co-culture of Faecalibacterium prausnitzii/Faecalibacterium duncaniae with colonic epithelium, antigen-presenting cells (APCs, herein dendritic cells and macrophages), and CD4+ naive T cells circulating underneath the colonic epithelium. In GuMI-APC condition, multiplex cytokine assays suggested that APCs contribute to the elevated level of cytokines and chemokines secreted into both apical and basolateral compartments compared to GuMI condition that lacks APC. In GuMI-APC with F. prausnitzii (GuMI-APC-FP), F. prausnitzii increased the transcription of pro-inflammatory genes such as toll-like receptor 1 (TLR1) and interferon alpha 1 (IFNA1) in the colonic epithelium, without a significant effect on cytokine secretion, compared to the GuMI-APC without bacteria (GuMI-APC-NB). In contrast, in the presence of CD4+ naive T cells (GuMI-APCT-FP), TLR1, IFNA1, and IDO1 transcription levels decreased with a simultaneous increase in F. prausnitzii-induced secretion of pro-inflammatory cytokines (e.g., IL8) compared to GuMI-APC-FP that lacks T cells. These results highlight the contribution of individual innate immune cells in regulating the immune response triggered by the gut commensal F. prausnitzii. The integration of defined populations of immune cells in the gut microphysiological system demonstrated the usefulness of GuMI physiomimetic platform to study microbe-epithelial-immune interactions in healthy and disease conditions.