Substrate calibration method of a computer-generated hologram based on ray propagation in a three-dimensional model.

In interferometry with a computer-generated hologram (CGH), the substrate error of the CGH limits its high-precision aspheric measurement application. The propagation form of the substrate error is still ambiguous although 0th-order calibration can partly correct it. We established the ray propagation in a three-dimensional model in order to solve the ambiguity of substrate error propagation. This method shows the modulation process of the CGH substrate error on the transmitted wavefront for the first time, until now, to the best of our knowledge. The experiments show that the propagation of the substrate error can be accurately analyzed, and the CGH design efficiency also is significantly improved after applying this method.

Multiple scenario land use simulation based on a coupled MOGA-PLUS model: a case of the Yellow River Basin.

Land use changes have profoundly influenced global environmental dynamics. The Yellow River (YR), as the world's fifth-longest river, significantly contributes to regional social and economic growth due to its extensive drainage area, making it a key global player. To ensure ecological stability and coordinate land use demand, modeling the future land allocation patterns of the Yellow River Basin (YRB) will assist in striking a balance between land use functions and the optimization of its spatial design, particularly in water and sand management. In this research, we used a multi-objective genetic algorithm (MOGA) with the PLUS model to simulate several different futures for the YRB's land use between 1990 and 2020 and predict its spatial pattern in 2030. An analysis of the spatiotemporal evolution of land use changes in the YRB indicated that construction land expansion is the primary driver of landscape pattern and structure changes and ecological degradation, with climate change also contributing to the expansion of the watershed area. On the other hand, the multi-scenario simulation, constrained by specific targets, revealed that economic development was mainly reflected in land expansion for construction. At the same time, grassland and woodland were essential pillars to support the region's ecological health, and increasing the development of unused land emerged as a potential pathway towards sustainable development in the region. This study could be used as a template for the long-term growth of other large river basins by elucidating the impacts of human activities on land use and rationalizing land resource allocation under various policy constraints.

Elastic Self-Recovering Hybrid Nanogenerator for Water Wave Energy Harvesting and Marine Environmental Monitoring.

To achieve large-scale development of triboelectric nanogenerators (TENGs) for water wave energy harvesting and powering the colossal sensors widely distributed in the ocean, facile and scalable TENGs with high output are urgently required. Here, an elastic self-recovering hybrid nanogenerator (ES-HNG) is proposed for water wave energy harvesting and marine environmental monitoring. The elastic skeletal support of the ES-HNG is manufactured using three-dimensional (3D) printing technology, which is more conducive to the large-scale integration of the ES-HNG. Moreover, the combination of a TENG and an electromagnetic generator (EMG) optimizes the utilization of device space, leading to enhanced energy harvesting efficiency. Experimental results demonstrate that the TENG achieves a peak power output of 42.68 mW, and the EMG reaches a peak power output of 4.40 mW. Furthermore, various marine environment monitoring sensors, such as a self-powered wireless meteorological monitoring system, a wireless alarm system, and a water quality monitoring pen, have been successfully powered by the sophisticated ES-HNG. This work introduces an ES-HNG for water wave energy harvesting, which demonstrates potential in marine environment monitoring and offers a new solution for the sustainable development of the marine internet of things.

Amount, distribution and controls of the soil organic carbon storage loss in the degraded China's grasslands.

More than 80 % of China's grasslands are classified as degraded, and the loss of soil carbon storage due to degradation has a significant impact on China's terrestrial carbon sinks as well as carbon neutrality targets. The loss of soil carbon storage in degraded grasslands can serve as a benchmark for quantifying the carbon sequestration capacity of restored grasslands in the future. Here, above- and below-ground biomass, soil organic carbon (SOC) content at various depths (0-100 cm) and soil bulk density were collected from 226 degradation sequences around China. The above information was integrated and statistically analyzed to quantify the difference of SOC storage between the degraded and natural grassland at national scale. The result showed that grassland degradation led to a significant reduction in SOC storage across different depths. SOC (0-100 cm) of degraded grassland decreased by 39 % compared to that of natural grassland, ranging from 21 % in the lightly degraded sites to 59 % of the extremely degraded sites. 15 potential predictors were used to estimate the national amount of these differences of 0-20 cm depth SOC storage as 5.29 ± 1.59 Pg C. This considerable carbon storage gap implies the necessity of China's grassland restoration project in achieving carbon neutrality goals in the future.

High-Fidelity Bioelectrodes with Bidirectional Ion-Electron Transduction Capability by Integrating Multiple Charge-Transfer Processes.

Bioelectronics is an exciting field that bridges the gap between physiological activities and external electronic devices, striving for high resolution, high conformability, scalability, and ease of integration. One crucial component in bioelectronics is bioelectrodes, designed to convert neural activity into electronic signals or vice versa. Previously reported bioelectrodes have struggled to meet several essential requirements simultaneously: high-fidelity signal transduction, high charge injection capability, strain resistance, and multifunctionality. This work introduces a novel strategy for fabricating superior bioelectrodes by merging multiple charge-transfer processes. The resulting bioelectrodes offer accurate ion-to-electron transduction for capturing electrophysiological signals, dependable charge injection capability for neuromodulation, consistent electrode potential for artifact rejection and biomolecule sensing, and high transparency for seamless integration with optoelectronics. Furthermore, the bioelectrode can be designed to be strain-insensitive by isolating signal transduction from electron transportation. The innovative concept presented in this work holds great promise for extending to other electrode materials and paves the way for the advancement of multimodal bioelectronics.

One-pot formal [3 + 2] annulation of 2-pyridinyl-substituted p-quinone methides and arynes for the synthesis of 3-aryl pyrido[1,2-a]indoles.

An efficient and metal-free method for the synthesis of 3-aryl pyrido[1,2-a]indoles from aryne intermediates and 2-pyridinyl-substituted p-QMs was successfully developed under ambient conditions. The reaction offered a novel and practical protocol to access some diverse functional molecules in good to excellent yields. The proposed mechanism indicated that the reaction proceeded via a formal [3 + 2] cycloaddition step.

High-Coupled Magnetic-Levitation Hybrid Nanogenerator with Frequency Multiplication Effect for Wireless Water Level Alarm.

Hybrid nanogenerators (HNGs) represent a promising avenue for water energy harvesting, yet their commercial viability faces hurdles such as limited power output, poor coupling, and constrained operational lifespans. Here, a highly coupled triboelectric-electromagnetic magnetic-levitation hybrid nanogenerator (ML-HNG) is introduced that shows great potential for water energy harvesting. The ML-HNG fulfills the challenges of high power output, strong coupling, and long operational lifespans. During the contact-separation process of the triboelectric nanogenerator (TENG), the changing magnetic flux in the electromagnetic generator's coils generates a potential difference between the coils and Cu electrodes. The unique design of the ML-HNG employs a shared coil electrode configuration, which enhances the coupling without adding extra volume. This integration allows the ML-HNG to achieve multi-frequency vibrations and multiple output cycles per external longitudinal movement, a phenomenon known as the frequency multiplication effect. With an average power density of 1.69 W m-3 in water, the ML-HNG provides continuous power for a thermo-hygrometer and can quickly drive a wireless water level alarm system within a minute. This groundbreaking hybrid nanogenerator design holds significant promise for the efficient and consistent harvesting of low-frequency ocean wave energy, marking a substantial advancement in blue energy technology.

Function Electrical Stimulation Effect on Muscle Fatigue Based on Fatigue Characteristic Curves of Dumbbell Weightlifting Training.

The parameter setting of functional electrical stimulation (FES) is important for active recovery training since it affects muscle health. Among the FES parameters, current amplitude is the most influential factor. To explore the FES effect on the maximum stimulation time, this study establishes a curve between FES current amplitude and the maximum stimulation time based on muscle fatigue. We collect 10 subjects' surface electromyography under dumbbell weightlifting training and analyze the muscle fatigue state by calculating the root mean square (RMS) of power. By analyzing signal RMS, the fatigue characteristic curves under different fatigue levels are obtained. According to the muscle response under FES, the relationship curve between the current amplitude and the maximum stimulation time is established and FES parameters' effect on the maximum stimulation time is obtained. The linear curve provides a reference for FES parameter setting, which can help to set stimulation time safely, thus preventing the muscles from entering an excessive fatigue state and becoming more active to muscle recovery training.

Preparatory movement state enhances premovement EEG representations for brain-computer interfaces.

Objective. Motor-related brain-computer interface (BCI) have a broad range of applications, with the detection of premovement intentions being a prominent use case. However, the electroencephalography (EEG) features during the premovement phase are not distinctly evident and are susceptible to attentional influences. These limitations impede the enhancement of performance in motor-based BCI. The objective of this study is to establish a premovement BCI encoding paradigm that integrates the preparatory movement state and validates its feasibility in improving the detection of movement intentions.Methods. Two button tasks were designed to induce subjects into a preparation state for two movement intentions (left and right) based on visual guidance, in contrast to spontaneous premovement. The low frequency movement-related cortical potentials (MRCPs) and high frequency event-related desynchronization (ERD) EEG data of 14 subjects were recorded. Extracted features were fused and classified using task related common spatial patterns (CSP) and CSP algorithms. Differences between prepared premovement and spontaneous premovement were compared in terms of time domain, frequency domain, and classification accuracy.Results. In the time domain, MRCPs features reveal that prepared premovement induce lower amplitude and earlier latency on both contralateral and ipsilateral motor cortex compared to spontaneous premovement, with susceptibility to the dominant hand's influence. Frequency domain ERD features indicate that prepared premovement induce lower ERD values bilaterally, and the ERD recovery speed after button press is the fastest. By using the fusion approach, the classification accuracy increased from 78.92% for spontaneous premovement to 83.59% for prepared premovement (p< 0.05). Along with the 4.67% improvement in classification accuracy, the standard deviation decreased by 0.95.Significance. The research findings confirm that incorporating a preparatory state into premovement enhances neural representations related to movement. This encoding enhancement paradigm effectively improves the performance of motor-based BCI. Additionally, this concept has the potential to broaden the range of decodable movement intentions and related information in motor-related BCI.

Mitochondrial dysfunction is associated with cognitive impairment in adults with OSA without dementia.

STUDY OBJECTIVES: Increased reactive oxygen species associated with loss of mitochondrial function affect synaptic activity, which is an important mechanism underlying cognitive decline. This study assesses the role of mitochondrial proteins in neuron-derived exosomes (NDEs) on cognitive impairment in patients with obstructive sleep apnea (OSA) without dementia. METHODS: Analyses were conducted in 268 study participants with complete polysomnography data, cognitive tests, and important clinical data available. NDEs were isolated immunochemically for enzyme-linked immunosorbent assay quantification of mitochondrial proteins, i.e., humanin and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), and synaptic protein, i.e., neurogranin (NRGN). A mediation analysis of the relationship between sleep parameters and cognition was performed using humanin, MOTS-c, and NRGN values as a mediating factor. Twenty-two patients with moderate to severe OSA who received CPAP therapy were followed up, and humanin, MOTS-c and NRGN levels were reassessed after 1 year of treatment. RESULTS: All participants were divided into the OSA + MCI group (n = 91), OSA-MCI group (n = 89), MCI group (MCI without OSA) (n = 38) and control group (normal cognitive state without OSA) (n = 50). The mean CD63-normalized NDE levels of humanin, MOTS-c, and NRGN in the OSA + MCI group were higher than those in the OSA-MCI and control groups. The NDE levels of humanin, MOTS-c, and NRGN in the MCI group were lower than those in controls. The odds of cognitive impairment in patients with OSA were higher with higher NDE levels of humanin, MOTS-c, and NRGN (odds ratio (OR): 2.100, 95 % confidence interval (CI): 1.646-2.679, P < 0.001; OR: 5.453, 95 % CI: 3.112-9.556, P < 0.001; OR: 3.115, 95 % CI: 2.163-4.484, P < 0.001). The impaired cognitive performance was associated with higher NDE levels of humanin (ß: 0.505, SE: 0.048, P < 0.001), MOTS-c (ß: 0.580, SE: 0.001, P < 0.001), and NRGN (ß: 0.585, SE: 0.553, P < 0.001). The relationship between sleep parameters (mean SaO2 and T90) and MoCA scores was mediated by the NDE levels of humanin, MOTS-c, and NRGN with the proportion of mediation varying from 35.33 % to 149.07 %. Receiver operating characteristic curve revealed an area under the curve of 0.905 for humanin, 0.873 for MOTS-c, and 0.934 for NRGN to predict MCI in OSA patients without dementia. Increased humanin, MOTS-c, and NRGN levels significantly decreased after CPAP treatment. CONCLUSIONS: Mitochondrial dysfunction is implicated in cognitive impairment in OSA patients without dementia, and mainly mediates the association between intermittent hypoxia and cognitive impairment in adults with OSA without dementia. Mitochondrial dysfunction can be partially reversible by CPAP treatment. Mitochondrial proteins can be used as markers of cognitive impairment in patients with OSA.

CMOS Scaling for the 5 nm Node and Beyond: Device, Process and Technology.

After more than five decades, Moore's Law for transistors is approaching the end of the international technology roadmap of semiconductors (ITRS). The fate of complementary metal oxide semiconductor (CMOS) architecture has become increasingly unknown. In this era, 3D transistors in the form of gate-all-around (GAA) transistors are being considered as an excellent solution to scaling down beyond the 5 nm technology node, which solves the difficulties of carrier transport in the channel region which are mainly rooted in short channel effects (SCEs). In parallel to Moore, during the last two decades, transistors with a fully depleted SOI (FDSOI) design have also been processed for low-power electronics. Among all the possible designs, there are also tunneling field-effect transistors (TFETs), which offer very low power consumption and decent electrical characteristics. This review article presents new transistor designs, along with the integration of electronics and photonics, simulation methods, and continuation of CMOS process technology to the 5 nm technology node and beyond. The content highlights the innovative methods, challenges, and difficulties in device processing and design, as well as how to apply suitable metrology techniques as a tool to find out the imperfections and lattice distortions, strain status, and composition in the device structures.

Antitumour effects of artesunate via cell cycle checkpoint controls in human oesophageal squamous carcinoma cells.

Artesunate (ART), an effective antimalarial semisynthetic derivative of artemisinin, exhibits antitumour properties, but the mechanism(s) involved remain elusive. In this study, we investigated the antitumour effects of ART on human oesophageal squamous cell carcinoma (ESCC) cell lines. Treatment of ESCC cell lines with ART resulted in the production of excessive reactive oxygen species (ROS) that induced DNA damage, reduced cell proliferation and inhibited clonogenicity via G1-S cell cycle arrest and/or apoptosis in vitro. The administration of ART to nude mice with ESCC cell xenografts inhibited tumour formation in vivo. However, the cytotoxicity of ART strongly differed among the ESCC cell lines tested. Transcriptomic profiling revealed that although the expression of large numbers of genes in ESCC cell lines was affected by ART treatment, these genes could be functionally clustered into pathways involved in regulating cell cycle progression, DNA metabolism and apoptosis. We revealed that p53 and Cdk4/6-p16-Rb cell cycle checkpoint controls were critical determinants required for mediating ART cytotoxicity in ESCC cell lines. Specifically, KYSE30 cells with p53Mut/p16Mut were the most sensitive to ART, KYSE150 and KYSE180 cells with p53Mut/p16Nor exhibited intermediate responses to ART, and Eca109 cells with p53Nor/p16Nor exhibited the most resistance to ATR. Consistently, perturbation of p53 expression using RNA interference (RNAi) and/or Cdk4/6 activity using the inhibitor palbociclib altered ART cytotoxicity in KYSE30 cells. Given that the p53 and Cdk4/6-cyclin D1-p16-Rb genes are commonly mutated in ESCC, our results potentially shed new light on neoadjuvant chemotherapy strategies for ESCC.

Cu(I)-Catalyzed Three-Component Annulation for the Synthesis of 3-Acyl Imidazo[1, 5-a]Pyridines from 2-Pyridinyl-Substituted p-Quinone Methides, Terminal Alkynes, and TsN3 Using O2 as the Oxygen Source.

Currently, most conventional methods to achieve imidazo[1,5-a]pyridines have limitations for the synthesis of 3-acyl imidazo[1,5-a]pyridines. Herein, a novel and efficient Cu(I)-catalyzed three-component annulation method for the synthesis of valuable 3-acyl imidazo[1,5-a]pyridines by the reaction of 2-pyridinyl-substituted p-QMs, terminal alkynes, and TsN3 in the presence of O2 under mild conditions have successfully been developed. The investigation indicated that molecular oxygen (O2) and TsN3, respectively, serving as oxygen and nitrogen sources, were essential for the successful completion of the reaction system.

The effect of trisomic chromosomes on spatial genome organization and global transcription in embryonic stem cells.

Aneuploidy frequently occurs in cancer and developmental diseases such as Down syndrome, with its functional consequences implicated in dosage effects on gene expression and global perturbation of stress response and cell proliferation pathways. However, how aneuploidy affects spatial genome organization remains less understood. In this study, we addressed this question by utilizing the previously established isogenic wild-type (WT) and trisomic mouse embryonic stem cells (mESCs). We employed a combination of Hi-C, RNA-seq, chromosome painting and nascent RNA imaging technologies to compare the spatial genome structures and gene transcription among these cells. We found that trisomy has little effect on spatial genome organization at the level of A/B compartment or topologically associating domain (TAD). Inter-chromosomal interactions are associated with chromosome regions with high gene density, active histone modifications and high transcription levels, which are confirmed by imaging. Imaging also revealed contracted chromosome volume and weakened transcriptional activity for trisomic chromosomes, suggesting potential implications for the transcriptional output of these chromosomes. Our data resources and findings may contribute to a better understanding of the consequences of aneuploidy from the angle of spatial genome organization.

A robust multi-branch multi-attention-mechanism EEGNet for motor imagery BCI decoding.

BACKGROUND: Motor-Imagery-based Brain-Computer Interface (MI-BCI) is a promising technology to assist communication, movement, and neurological rehabilitation for motor-impaired individuals. Electroencephalography (EEG) decoding techniques using deep learning (DL) possess noteworthy advantages due to automatic feature extraction and end-to-end learning. However, the DL-based EEG decoding models tend to show large variations due to intersubject variability of EEG, which results from inconsistencies of different subjects' optimal hyperparameters. NEW METHODS: This study proposes a multi-branch multi-attention mechanism EEGNet model (MBMANet) for robust decoding. It applies the multi-branch EEGNet structure to achieve various feature extractions. Further, the different attention mechanisms introduced in each branch attain diverse adaptive weight adjustments. This combination of multi-branch and multi-attention mechanisms allows for multi-level feature fusion to provide robust decoding for different subjects. RESULTS: The MBMANet model has a four-classification accuracy of 83.18% and kappa of 0.776 on the BCI Competition IV-2a dataset, which outperforms other eight CNN-based decoding models. This consistently satisfactory performance across all nine subjects indicates that the proposed model is robust. CONCLUSIONS: The combine of multi-branch and multi-attention mechanisms empowers the DL-based models to adaptively learn different EEG features, which provides a feasible solution for dealing with data variability. It also gives the MBMANet model more accurate decoding of motion intentions and lower training costs, thus improving the MI-BCI's utility and robustness.

Transcriptomic Analysis of Type 2 Diabetes Mellitus Combined with Lower Extremity Atherosclerotic Occlusive Disease.

Background: The pathological damage mechanism of type 2 diabetes (T2D) and macroangiopathy is extremely complex, and T2D and arteriosclerosis obliterans have different biological behaviors and clinical features. To explore the mechanism of lower extremity arteriosclerosis occlusion (LEAOD) in T2D patients, we utilized RNA-seq to identify unique gene expression signatures of T2D and LEAOD through transcriptomic analysis. Methods: We obtained blood samples and performed RNA sequencing from four patients with T2D, five of whom had LEAOD. Another six age- and gender-matched blood samples from healthy volunteers were used for control. By exploring the general and specific differential expression analysis after transcriptome sequencing, specific gene expression patterns of T2D and LEAOD were verified. Results: Transcriptome analysis found differentially expressed genes in T2D, and T2D + LEAOD (vs normal) separately, of which 35/486 (T2D/T2D + LEAOD) were up-regulated and 1290/2970 (T2D/T2D + LEAOD) were down-regulated. A strong overlap of 571 genes across T2D, LEAOD, and coexisting conditions was mainly involved in extracellular exosomes and the transcription process. By exploring the sex difference gene expression features between T2D, T2D + LEAOD, and healthy controls, we noticed that sex chromosome-associated genes do not participate in the sexual dimorphism gene expression profiles of T2D and LEAOD. Protein-Protein Interaction Network analysis and drug target prediction provided the drug candidates to treat T2D and LEAOD. Conclusion: This study provides some evidence at the transcript level to uncover the association of T2D with LEAOD. The screened hub genes and predicted target drugs may be therapeutic targets.

Advanced glycation end products regulate macrophage apoptosis and influence the healing of diabetic foot wound through miR-361-3p/CSF1R and PI3K/AKT pathway.

Background: Diabetic foot ulcers (DFUs) are a severe complication of diabetes. Persistent inflammation and impaired vascularization present considerable challenges in tissue wound healing. The aim of this study was to identify the crucial regulators of DFU wound healing and investigate their specific mechanisms in DFU. Methods: DFU RNA sequencing data were obtained to identify crucial feature genes. The expression levels of the feature genes and their corresponding microRNAs (miRNAs) were verified in clinical samples. Subsequently, the expression of CD68 was determined in DFU and non-diabetic foot skin samples. RAW 264.7 cells were treated with advanced glycation end products (AGEs) to determine their viability and apoptosis. Finally, the roles of the selected crucial genes and their corresponding miRNAs were investigated using in vitro experiments and a mouse model of diabetes. Results: Bioinformatic analysis showed that five crucial feature genes (CORO1A, CSF1R, CTSH, NFE2L3, and SLC16A10) were associated with DFU wound healing. The expression validation showed that miR-361-3p-CSF1R had a significant negative correlation and was thus selected for further experiments. AGEs significantly inhibited the viability of RAW 264.7 cells and enhanced their apoptosis; furthermore, the AGEs significantly downregulated CSF1R and increased miR-361-3p levels compared with the control cells. Additionally, inhibition of miR-361-3p decreased the cell apoptosis caused by AGEs and increased the levels of p-AKT/AKT and p-PI3K/PI3K, whereas CSF1R knockdown reversed the effects of miR-361-3p. In vivo experiments showed that miR-361-3p inhibition promoted wound healing in diabetic mice and regulated PI3K/AKT levels. Conclusions: AGEs may regulate macrophage apoptosis via the miR-361-3p/CSF1R axis and PI3K/AKT pathway, thereby influencing DFU wound healing.

Novel Multitarget ACE Inhibitory Peptides from Bovine Colostrum Immunoglobulin G: Cellular Transport, Efficacy in Regulating Endothelial Dysfunction, and Network Pharmacology Studies.

In this study, we used traditional laboratory methods, bioinformatics, and cellular models to screen novel ACE inhibitory (ACEI) peptides with strong ACEI activity, moderate absorption rates, and multiple targets from bovine colostrum immunoglobulin G (IgG). The purified fraction of the compound proteinase hydrolysate of IgG showed good ACEI activity. After nano-UPLC-MS/MS identification and in silico analysis, eight peptides were synthesized and verified. Among them, SFYPDY, TSFYPDY, FSWF, WYQQVPGSGL, and GVHTFP were identified as ACEI peptides, as they exhibited strong ACEI activity (with IC50 values of 104.7, 80.0, 121.2, 39.8, and 86.3 µM, respectively). They displayed good stability in an in vitro simulated gastrointestinal digestion assay. In a Caco-2 monolayer model, SFYPDY, FSWF, and WYQQVPGSGL exhibited better absorption rates and lower IC50 values than the other peptides and were thereby identified as novel ACEI peptides. Subsequently, in a H2O2-induced endothelial dysfunction (ED) model based on HUVECs, SFYPDY, FSWF, and WYQQVPGSGL regulated ED by reducing apoptosis and ROS accumulation while upregulating NOS3 mRNA expression. Network pharmacology analysis and RT-qPCR confirmed that they regulated multiple targets. Overall, our results suggest that SFYPDY, FSWF, and WYQQVPGSGL can serve as novel multitarget ACEI peptides.

Microbial metabolite trimethylamine-N-oxide induces intestinal carcinogenesis through inhibiting farnesoid X receptor signaling.

PURPOSE: Microbial dysbiosis is considered as a hallmark of colorectal cancer (CRC). Trimethylamine-N-oxide (TMAO) as a gut microbiota-dependent metabolite has recently been implicated in CRC development. Nevertheless, evidence relating TMAO to intestinal carcinogenesis remains largely unexplored. Herein, we aimed to examine the crucial role of TMAO in CRC progression. METHODS: Apcmin/+ mice were treated with TMAO or sterile PBS for 14 weeks. Intestinal tissues were isolated to evaluate the effects of TMAO on the malignant transformation of intestinal adenoma. The gut microbiota of mouse feces was detected by 16S rRNA sequencing analysis. HCT-116 cells were used to provide further evidence of TMAO on the progression of CRC. RESULTS: TMAO administration increased tumor cell and stem cell proliferation, and decreased apoptosis, accompanied by DNA damage and gut barrier impairment. Gut microbiota analysis revealed that TMAO induced changes in the intestinal microbial community structure, manifested as reduced beneficial bacteria. Mechanistically, TMAO bound to farnesoid X receptor (FXR), thereby inhibiting the FXR-fibroblast growth factor 15 (FGF15) axis and activating the Wnt/ß-catenin signaling pathway, whereas the FXR agonist GW4064 could blunt TMAO-induced Wnt/ß-catenin pathway activation. CONCLUSION: The microbial metabolite TMAO can enhance intestinal carcinogenesis by inhibiting the FXR-FGF15 pathway.