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Innate lymphoid cells (ILCs) and CD4 + T cells produce IL-22, which is critical for intestinal immunity. The microbiota is central to IL-22 production in the intestines; however, the factors that regulate IL-22 production by CD4 + T cells and ILCs are not clear. Here, we show that microbiota-derived short-chain fatty acids (SCFAs) promote IL-22 production by CD4 + T cells and ILCs through G-protein receptor 41 (GPR41) and inhibiting histone deacetylase (HDAC). SCFAs upregulate IL-22 production by promoting aryl hydrocarbon receptor (AhR) and hypoxia-inducible factor 1α (HIF1α) expression, which are differentially regulated by mTOR and Stat3. HIF1α binds directly to the Il22 promoter, and SCFAs increase HIF1α binding to the Il22 promoter through histone modification. SCFA supplementation enhances IL-22 production, which protects intestines from inflammation. SCFAs promote human CD4 + T cell IL-22 production. These findings establish the roles of SCFAs in inducing IL-22 production in CD4 + T cells and ILCs to maintain intestinal homeostasis. Intestinal IL-22 has important regulatory effects on the barrier and intestinal diseases and its production is controlled by the intestinal microbiome. Here the authors show that intestinal immune cell production of IL-22 is regulated by short chain fatty acids via an aryl hydrocarbon receptor and HIF1α-mediated mechanism that protects mice from intestinal inflammation.

T-cells are crucial in maintanence of intestinal homeostasis, however, it is still unclear how microbiota metabolites regulate T-effector cells. Here we show gut microbiota-derived short-chain fatty acids (SCFAs) promote microbiota antigen-specific Th1 cell IL-10 production, mediated by G-protein coupled receptors 43 (GPR43). Microbiota antigen-specific Gpr43 −/− CBir1 transgenic (Tg) Th1 cells, specific for microbiota antigen CBir1 flagellin, induce more severe colitis compared with wide type (WT) CBir1 Tg Th1 cells in Rag −/− recipient mice. Treatment with SCFAs limits colitis induction by promoting IL-10 production, and administration of anti-IL-10R antibody promotes colitis development. Mechanistically, SCFAs activate Th1 cell STAT3 and mTOR, and consequently upregulate transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1), which mediates SCFA-induction of IL-10. SCFA-treated Blimp1 −/− Th1 cells produce less IL-10 and induce more severe colitis compared to SCFA-treated WT Th1 cells. Our studies, thus, provide insight into how microbiota metabolites regulate Th1 cell functions to maintain intestinal homeostasis. T cells play a critical role in intestinal homeostasis, with increasing evidence suggesting a role for the microbiome metabolome in modulating this response. Here the authors show short-chain fatty acids promote IL-10 production in Th1 cells.

Accurate semantic segmentation and automatic thickness measurement of the glomerular basement membrane (GBM) can aid pathologists in carrying out subsequent pathological diagnoses. The GBM has a complex ultrastructure and irregular shape, which makes it difficult to segment accurately. We found that the shape of the GBM is striped, so we proposed an RSP model to extract both the strip and square features of the GBM. Additionally, grayscale images of the GBM are similar to those of surrounding tissues, and the contrast is low. We added an edge attention mechanism to further improve the quality of segmentation. Moreover, we revised the pixel-level loss function to consider the tissues around the GBM and locate the GBM as a doctor would, i.e., by using the tissues as the reference object. Ablation experiments with each module showed that SSPNet can better segment the GBM. The proposed method was also compared with the existing medical semantic segmentation model. The experimental results showed that the proposed method can obtain high-precision segmentation results for the GBM and completely segment the target. Finally, the thickness of the GBM was calculated using a skeleton extraction method to provide quantitative data for expert diagnosis.

How the gut microbiota regulates intestinal homeostasis is not completely clear. Gut microbiota metabolite short-chain fatty acids (SCFAs) have been reported to regulate T-cell differentiation. However, the mechanisms underlying SCFA regulation of T-cell differentiation and function remain to be investigated. CBir1, an immunodominant microbiota antigen, transgenic T cells were treated with butyrate under various T-cell polarization conditions to investigate butyrate regulation of T-cell differentiation and the mechanism involved. Transfer of butyrate-treated CBir T cells into Rag1-/- mice was performed to study the in vivo role of such T cells in inducing colitis. Although butyrate promoted Th1 cell development by promoting IFN-γ and T-bet expression, it inhibited Th17 cell development by suppressing IL-17, Rorα, and Rorγt expression. Interestingly, butyrate upregulated IL-10 production in T cells both under Th1 and Th17 cell conditions. Furthermore, butyrate induced T-cell B-lymphocyte-induced maturation protein 1 (Blimp1) expression, and deficiency of Blimp1 in T cells impaired the butyrate upregulation of IL-10 production, indicating that butyrate promotes T-cell IL-10 production at least partially through Blimp1. Rag1-/- mice transferred with butyrate-treated T cells demonstrated less severe colitis, compared with transfer of untreated T cells, and administration of anti-IL-10R antibody exacerbated colitis development in Rag-/- mice that had received butyrate-treated T cells. Mechanistically, the effects of butyrate on the development of Th1 cells was through inhibition of histone deacetylase but was independent of GPR43. These data indicate that butyrate controls the capacity of T cells in the induction of colitis by differentially regulating Th1 and Th17 cell differentiation and promoting IL-10 production, providing insights into butyrate as a potential therapeutic for the treatment of inflammatory bowel disease.

The early screening of depression is highly beneficial for patients to obtain better diagnosis and treatment. While the effectiveness of utilizing voice data for depression detection has been demonstrated, the issue of insufficient dataset size remains unresolved. Therefore, we propose an artificial intelligence method to effectively identify depression. The wav2vec 2.0 voice-based pre-training model was used as a feature extractor to automatically extract high-quality voice features from raw audio. Additionally, a small fine-tuning network was used as a classification model to output depression classification results. Subsequently, the proposed model was fine-tuned on the DAIC-WOZ dataset and achieved excellent classification results. Notably, the model demonstrated outstanding performance in binary classification, attaining an accuracy of 0.9649 and an RMSE of 0.1875 on the test set. Similarly, impressive results were obtained in multi-classification, with an accuracy of 0.9481 and an RMSE of 0.3810. The wav2vec 2.0 model was first used for depression recognition and showed strong generalization ability. The method is simple, practical, and applicable, which can assist doctors in the early screening of depression.

The antimicrobial peptides (AMP) produced by intestinal epithelial cells (IEC) play crucial roles in the regulation of intestinal homeostasis by controlling microbiota. Gut microbiota has been shown to promote IEC expression of RegIIIγ and certain defensins. However, the mechanisms involved are still not completely understood. In this report, we found that IEC expression levels of RegIIIγ and β-defensins 1, 3, and 4 were lower in G protein-coupled receptor (GPR)43−/− mice compared to that of wild-type (WT) mice. Oral feeding with short-chain fatty acids (SCFA) promoted IEC production of RegIIIγ and defensins in mice. Furthermore, SCFA induced RegIIIγ and β-defensins in intestinal epithelial enteroids generated from WT but not GPR43−/− mice. Mechanistically, SCFA activated mTOR and STAT3 in IEC, and knockdown of mTOR and STAT3 impaired SCFA induction of AMP production. Our studies thus demonstrated that microbiota metabolites SCFA promoted IEC RegIIIγ and β-defensins in a GPR43-dependent manner. The data thereby provide a novel pathway by which microbiota regulates IEC expression of AMP and intestinal homeostasis.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide.1 While genetic mutations have long been recognised as key drivers of CRC development, the substantial role of environmental factors, particularly the gut microbiome, in shaping cancer phenotypes has emerged as a critical area of investigation. In recent years, mounting evidence has linked gut microbial dysbiosis to CRC by modulating the mucosa through the reprogramming of host gene expression, promoting inflammatory pathways and contributing to barrier dysfunction.2 The interplay between microbiome, host immunity and epigenetic regulation is now recognised as a central axis in host gene reprogramming and predisposition to CRC.3 However, the molecular mechanisms underlying these interactions remain incompletely understood.

The Qiongdongnan Basin constitutes a sedimentary basin characterized by elevated temperatures, significant overpressures, and abundant hydrocarbons. Investigations within this basin have identified hydrothermal fluid movements linked to overpressure conditions, comprising two vertically separated overpressured intervals. The shallow overpressure compartment is principally caused by a combination of undercompaction and clay diagenesis. In contrast, the deeper high-pressure compartment results from hydrocarbon gas generation. Numerical pressure modeling indicates late-stage (post-5 Ma) development of significant overpressure within the deep compartment. It is proposed that accelerated subsidence in the Pliocene-Quaternary initiated substantial gas generation, thereby promoting the formation of the deep overpressured system. Multiple organic maturation parameters, combined with fluid inclusion microthermometry, reveal a thermal anomaly adjacent to the upper boundary of the deep overpressured zone. This anomaly indicates vertical transport of hydrothermal fluids ascending from the underlying high-pressure zone. Laser Raman spectroscopy confirms the presence of both hydrocarbons and carbon dioxide within these migrating fluids. Integration of fluid inclusion thermometry with burial history modeling constrains the timing of hydrocarbon-carrying fluid charge to the interval from 4.2 Ma onward, synchronous with modeled peak gas generation and a phase of pronounced overpressure buildup. We propose that upon exceeding the fracture gradient threshold, fluid pressure triggered upward migration of deeply sourced, hydrocarbon-enriched fluids through hydrofracturing pathways. This process led to localized dissolution and fracturing near the top of the deep overpressured system, while simultaneously facilitating significant hydrocarbon accumulation and forming preferential accumulation zones. These findings provide critical insights into petroleum exploration in overpressured sedimentary basins.

To meet the demand of not interrupting traffic during the replacement of suspenders in long-span railway suspension bridges, this research proposes for the first time the application of the unsupported replacement method to the suspender replacement of self-anchored railway suspension bridges. Based on the basic principle of suspension bridge, the safety control index in the process of boom replacement is proposed. Midas Civil 2024 software is used to analyze the structural response of the boom after removal under static force and train load, including the change of cable force of adjacent boom, the displacement of main cable and stiffening beam. The real bridge test was carried out based on the special bridge of Chongqing Egongyan Track. The results show that after the removal of the boom, the cable force of the adjacent boom increases by 42–55%, the main cable is partially twisted but the adjacent joints change little, and the displacement of the stiffened beam meets the specification requirements. When the train is fully loaded, the maximum increase of the cable force of the adjacent boom is 150 kN, the stress increment of the operating boom is far less than the design strength, the increase of the downtorsion of the main cable is only 2.22%, and the displacement of the stiffening beam is within the allowable range. The safety control index and real bridge test results show that the unsupported replacement method is feasible and safe in the replacement of the suspenders of long-span rail suspension bridges, which provides an important reference for related projects.

The track-specific bridge has the characteristics of a large volume of passenger traffic, narrow transverse width, and large excitation. The long-term and high-frequency operating conditions put forward strict requirements for the safety and comfort of the bridge. Aiming at the problem of achieving fast, accurate, and intelligent evaluation of bridges under the coupling action of trains and temperatures, this paper proposes a method for evaluating the structural vertical stiffness of track-specific suspension bridges under the action of the no-load first train. Firstly, the f − v − t (deformation-velocity-time) data of trains on the bridge are analyzed through linkage numerical simulation, track train transponder, and structural safety monitoring system. Secondly, the CART algorithm establishes a regression model for data correction. The mapping relationship between the modified deformation monitoring value and the theoretical calculation value is analyzed to realize the current structural vertical stiffness evaluation. Finally, it is verified by the world’s largest span self-anchored track-specific suspension bridge. The results show that the theoretical deformation value of the most unfavorable deformation section is 268.55 mm, the actual monitoring value is 232.80 mm, the difference is 35.75 mm, and the relative error is 13.3%. The R2 score of the CART regression model is 0.94, and the accuracy of the CART regression model is higher than that of other algorithm regression models. The modified dynamic check coefficient is less than 1, and the ratio of the modified residual deformation value to the maximum deformation value is 7.6%, which meets the specification requirement not exceeding 20%, indicating that the current structural vertical stiffness is in normal operating conditions.