The alteration of mucosal bile acid profile is associated with nerve growth factor expression in mast cells and bowel symptoms in diarrhea-predominant irritable bowel syndrome.

Mucosal bile acid (BA) profile is still unestablished in diarrhea-predominant irritable bowel syndrome (IBS-D). The aim of this study was to explore colonic mucosal BAs and their associations with mucosal mast cell (MMC)-derived nerve growth factor (NGF) and bowel symptoms in IBS-D. Colonic mucosal biopsies from 36 IBS-D patients and 35 healthy controls (HCs) were obtained for targeted BA profiling. MMC count and the expression of NGF and tight junction proteins (TJPs) were examined. We found that colonic mucosal BA profile was altered in the IBS-D cohort. The proportion of primary BAs was significantly higher and that of secondary BAs was lower in IBS-D patients. According to the 90th percentile of total mucosal BA content of HCs, IBS-D patients were divided into BA-H (n = 7, 19.4%) and BA-L (n = 29, 80.6%) subgroups. BA-H patients showed significantly higher total mucosal BA content compared to BA-L subgroup and HCs. The mucosal content of 11 BA metabolites significantly increased in BA-H subgroup, e.g. cholic acid (CA) and taurocholic acid (TCA). Moreover, BA-H patients displayed significantly elevated MMC count and NGF expression, with decreased expression of TJPs (claudin-1, junctional adhesion molecule-A and zonula occludens-1). Correlation analyses revealed that mucosal TCA content positively correlated with MMC count, MMC-derived NGF levels, and abdominal pain while negatively correlated with TJP expression. In conclusion, IBS-D patients showed an altered BA profile in the colonic mucosa. Approximately 20% of them exhibit elevated mucosal BA content, which may be associated with MMC-derived NGF signaling and bowel symptoms.

Unsupervised reconstruction with a registered time-unsheared image constraint for compressed ultrafast photography.

Compressed ultrafast photography (CUP) is a computational imaging technology capable of capturing transient scenes in picosecond scale with a sequence depth of hundreds of frames. Since the inverse problem of CUP is an ill-posed problem, it is challenging to further improve the reconstruction quality under the condition of high noise level and compression ratio. In addition, there are many articles adding an external charge-coupled device (CCD) camera to the CUP system to form the time-unsheared view because the added constraint can improve the reconstruction quality of images. However, since the images are collected by different cameras, slight affine transformation may have great impacts on the reconstruction quality. Here, we propose an algorithm that combines the time-unsheared image constraint CUP system with unsupervised neural networks. Image registration network is also introduced into the network framework to learn the affine transformation parameters of input images. The proposed algorithm effectively utilizes the implicit image prior in the neural network as well as the extra hardware prior information brought by the time-unsheared view. Combined with image registration network, this joint learning model enables our proposed algorithm to further improve the quality of reconstructed images without training datasets. The simulation and experiment results demonstrate the application prospect of our algorithm in ultrafast event capture.

Snapshot compressive imaging at 855 million frames per second for aluminium planar wire array Z-pinch.

This paper present a novel, integrated compressed ultrafast photography system for comprehensive measurement of the aluminium planar wire array Z-Pinch evolution process. The system incorporates a large array streak camera and embedded encoding to improve the signal-to-noise ratio. Based on the "QiangGuang-I" pulsed power facility, we recorded the complete continuous 2D implosion process of planar wire array Z-Pinch for the first time. Our results contribute valuable understanding of imploding plasma instabilities and offer direction for the optimization of Z-Pinch facilities.

Measurement of nanocomposite scintillators by terahertz time domain spectroscopy.

Nanocomposite scintillators are expected to combine the advantages of inorganic and plastic scintillators, such as high detection efficiency, high light yield, fast decay time, low cost, and ease of processing. They are currently the forefront and hot field of scintillator research. In this study, a non-destructive method was developed for measuring the content of inorganic components in nanocomposite scintillators by terahertz time-domain spectroscopy. The complex refractive index of B a F 2 nanocomposite scintillators with different mass contents was measured in the terahertz band. As the mass content of B a F 2 nanoparticles increases, the refractive index and extinction coefficient of B a F 2 nanocomposite scintillators also gradually increase in the terahertz band. By combining the effective medium theory, the expected mass content was obtained, proving the feasibility of this measuring method.

Experimental Demonstration of a Tunable Energy-Selective Gamma-Ray Imaging System Based on Recoil Electrons.

The domain of gamma-ray imaging necessitates technological advancements to surmount the challenge of energy-selective imaging. Conventional systems are constrained in their dynamic focus on specific energy ranges, a capability imperative for differentiating gamma-ray emissions from diverse sources. This investigation introduces an innovative imaging system predicated on the detection of recoil electrons, addressing the demand for adjustable energy selectivity. Our methodology encompasses the design of a gamma-ray imaging system that leverages recoil electron detection to execute energy-selective imaging. The system's efficacy was investigated experimentally, with emphasis on the adaptability of the energy selection window. The experimental outcomes underscore the system's adeptness at modulating the energy selection window, adeptly discriminating gamma rays across a stipulated energy spectrum. The results corroborate the system's adaptability, with an adjustable energy resolution that coincides with theoretical projections and satisfies the established criteria. This study affirms the viability and merits of utilizing recoil electrons for tunable energy-selective gamma-ray imaging. The system's conceptualization and empirical validation represent a notable progress in gamma-ray imaging technology, with prospective applications extending from medical imaging to astrophysics. This research sets a solid foundation for subsequent inquiries and advancements in this domain.

APOE ε4-associated downregulation of the IL-7/IL-7R pathway in effector memory T cells: Implications for Alzheimer's disease.

INTRODUCTION: The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. METHODS: The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). RESULTS: Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. DISCUSSION: These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. HIGHLIGHTS: The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.

[Preparation and effectiveness evaluation of placebo of Jiawei Ermiao Granules].

This study explored the preparation process of the placebo of Jiawei Ermiao Granules and evaluated the placebo effect, aiming to provide qualified placebo samples for clinical trials of Jiawei Ermiao Granules and a reference for the preparation and quality evaluation of placebos of traditional Chinese medicine granules. On the basis of the comprehensive analysis results of Jiawei Ermiao Granules, the orthogonal experiment was conducted to optimize the flavoring agents and colorants. After manual evaluation, the placebo formula was determined as dextrin 10 g, Codonopsis Radix extract 5.0 g, bitter melon extract 1.6 g, Mume Fructus extract 0.3 g, stevioside 0.1 g, sucrose octaacetate 0.004 g, indigo 0.004 g, lemon yellow 0.003 1 g, sunset yellow 0.001 8 g, bitter tea powder 0.001 8 g, caramel 0.001 3 g. Pilot trials were conducted on the placebo formula. The simulation effect of placebo was evaluated independently and comparatively, and the objectively evaluated by electronic nose and electronic tongue. The results showed that the independent manual evaluation of the placebo formula had higher error rate, and the placebo and Jiawei Ermiao Granules showed the similarity of 99.61% in the comparative manual evaluation. The smell similarity between the placebo and Jiawei Ermiao Granules was 99.19%, and the electronic tongue test showed little difference in the taste. In conclusion, the placebo prepared in this study shows a high similarity to Jiawei Ermiao Granules, which is not easy to break the blindness when being applied to clinical trials. This study provides a reference for the preparation and quality evaluation and promotes the large-scale production of placebos of traditional Chinese medicine granules, playing a role in improving the persuasiveness and acceptance of the efficacy of traditional Chinese medicines.

Self-Supporting Co/CeO2 Heterostructures for Ampere-Level Current Density Alkaline Water Electrolysis.

Remodeling the active surface through fabricating heterostructures can substantially enhance alkaline water electrolysis driven by renewable electrical energy. However, there are still great challenges in the synthesis of highly reactive and robust heterostructures to achieve both ampere-level current density hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Herein, we report a new Co/CeO2 heterojunction self-supported electrode for sustainable overall water splitting. The self-supporting Co/CeO2 heterostructures required only low overpotentials of 31.9 ± 2.2, 253.3 ± 2.7, and 316.7 ± 3 mV for HER and 214.1 ± 1.4, 362.3 ± 1.9, and 400.3 ± 3.7 mV for OER at 0.01, 0.5, and 1.0 A·cm-2, respectively, being one of the best Co-based bifunctional electrodes. Electrolyzer constructed from this electrode acting as an anode and cathode merely required cell voltages of 1.92 ± 0.02 V at 1.0 A·cm-2 for overall water splitting. Multiple characterization techniques combined with density functional theory calculations disclosed the different active sites on the anode and cathode, and the charge redistributions on the heterointerfaces that can optimize the adsorption of H and oxygen-containing intermediates, respectively. This study presents the tremendous prospective of self-supporting heterostructures for effective and economical overall water splitting.

Single-shot imaging with multiple frames through delaying optical images.

A single-shot imaging system with multiple frames has been developed, which can record sequential multiple frames by delaying multiple optical images with fiber bundles and then capturing the images with a single intensified camera. The observed optical object is imaged through four lenses onto the end faces of four sets of fiber bundles. These fiber bundles with different lengths can provide different delays for delivering optical images, which determine the inter-frame separation times. The optical images exported from the fiber bundles are captured with a single intensified CMOS camera simultaneously. This imaging system has been applied for investigating the dynamic x-ray spot of the rod-pinch diode via a combination of scintillators, which are used to convert x-ray images to optical images. Four sequential x-ray images in a single shot have been obtained, which show the dynamic development of the rod-pinch x-ray spot. The results experimentally reveal the dynamics of the electrons flow bombarding the rod, which roughly agrees with the theoretical modeling of the rod-pinch diode.

Intracellular C3 prevents hepatic steatosis by promoting autophagy and very-low-density lipoprotein secretion.

Complement component C3, mainly synthesized by hepatocytes, acts as the convergence point of three different pathways in activating the complement cascade. Besides its well-established roles in the extracellular milieu, C3 performs various intracellular functions such as immunomodulation and pathogen recognition. Although C3 is present at extremely high concentrations in hepatocytes, little is known about its intrahepatic function. In this study, we found that C3 knockout (C3-/- ) mice displayed accelerated hepatic triglyceride (TG) accumulation compared with C57BL/6J wild type mice. Mechanistically, C3 deficiency impaired lipophagy in hepatocytes, owing to the disrupted interaction between C3 and autophagy-related 16 like 1, which is essential for autolysosome assembly. Furthermore, lipophagy deficiency affected the function of the endoplasmic reticulum in C3-/- mice, subsequently affecting the expression of protein disulfide isomerase and activity of microsomal TG transfer protein, and ultimately impairing the production of hepatic very-low-density lipoproteins (VLDLs). Rapamycin and thapsigargin treatment accelerated VLDL secretion and alleviated hepatic lipid accumulation in C3-/- mice. Our study demonstrates that C3 promotes lipophagy to facilitate VLDL secretion in hepatocytes, thus playing an essential role in balancing TG levels in the liver.

Scutellarin ameliorates hepatic lipid accumulation by enhancing autophagy and suppressing IRE1α/XBP1 pathway.

Nonalcoholic fatty liver disease is the most prevalent liver disease characterized by excessive lipid accumulation in hepatocytes. Endoplasmic reticulum (ER) stress and autophagy play an important role in lipid accumulation. In this study, scutellarin (Scu) was examined in palmitic acid-treated HepG2 cells and C57/BL6 mice fed a high-fat diet (HFD). Scu reduced intracellular lipid content and inhibited sterol regulatory element binding protein-1c (SREBP-1c)-mediated lipid synthesis and fatty acid translocase-mediated lipid uptake in HepG2 cells. Additionally, Scu restored impaired autophagy and inhibited excessive activation of ER stress in vivo and in vitro. Moreover, Scu upregulated forkhead box O transcription factor 1-mediated autophagy by inhibiting inositol-requiring enzyme 1α (IRE1α)/X-box-binding protein 1 (XBP1) branch activation, while XBP1s overexpression exacerbated the lipid accumulation and impaired autophagy in HepG2 cells and also weakened the positive effects of Scu. Furthermore, Scu attenuated ER stress by activating autophagy, ultimately downregulating SREBP-1c-mediated lipid synthesis, and autophagy inhibitors offset these beneficial effects. Scu inhibited the crosstalk between autophagy and ER stress and downregulated saturated fatty acid-induced lipid accumulation in hepatocytes. These findings demonstrate that Scu ameliorates hepatic lipid accumulation by enhancing autophagy and suppressing ER stress via the IRE1α/XBP1 pathway.

Fluorescent Talarolactones from Talaromyces sp.

(+)-Talarolactone C (1), Talarolactone A (2), Talarolactone B (3, sulfoxide derivative), and Talarolactone D (4, sulfone derivative) were isolated from Talaromyces sp. which was cultured in rice medium with sodium butyrate. The structures of talarolactone analogs above were characterized by a combination of spectroscopic, X-ray crystallographic, and computational methods. These talarolactones and Talarolactone A sodium (5) with the same carbon skeleton showed different fluorescence characteristics.

Anti-inflammatory sesquiterpene dimers and diterpenes from the aerial part of Inula japonica.

Phytochemical investigation on the 95% alcohol extract of the aerial part of Inula japonica led to the isolation of three new compounds, inulanolides F-G (1-2) and 17α-carboxaldehyde-ent-kaur-18-oic acid (3), together with four known compounds (4-7). The structures of new compounds were elucidated by using spectroscopic data. Most of the isolated compounds showed significant anti-inflammatory activities.

Functional analysis of the long-range regulatory element of BMP2 gene.

Recently, several pedigree-based studies have shown that abnormal replication of an enhancer element regulatory region in the downstream of the bone morphogenetic protein 2 (BMP2) gene is the cause of brachydactyly type A2 (BDA2). However, the exact molecular function of this regulatory region is unclear, and even conflicting results have emerged. In this study, based on bioinformatics analysis, we amplified target fragments of different lengths in this regulatory region by PCR technology, including a highly conserved 2.1 kb core sequence and 3 fragments that can completely cover the core 2.1 kb fragment. Then, the gene recombination vectors were constructed, and the biological function of these fragments was analyzed by the dual-luciferase reporter gene technology system. We found that the highly conserved 2.1 kb fragment did not have enhancer activity, while all of three truncated fragments showed strong enhancer activity. The results suggest that the expression regulation mode of the BMP2 gene is very complex. For the downstream regulatory region, selecting fragments of different lengths may have different effects on the regulation of BMP2 expression, which may due to the fragments with different lengths carrying different regulatory elements in the number of types. In summary, this study revealed the complexity of BMP2 gene regulatory elements, and provided new clues and directions for the subsequent in-depth exploration of the molecular pathogenic mechanism of BDA2.

Universal and Programmable Rolling Circle Amplification-CRISPR/Cas12a-Mediated Immobilization-Free Electrochemical Biosensor.

The development of a sensing platform with high sensitivity and specificity, especially programmability and universal applicability, for the detection of clinically relevant molecules is highly valuable for disease monitoring and confirmation but remains a challenge. Here, for the first time, we introduce the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system into an immobilization-free electrochemical biosensing platform for sensitively and specifically detecting the disease-related nucleic acids and small molecules. In this strategy, a modular rolling circle amplification (RCA) is designed to transform and amplify the target recognition event into the universal trigger DNA strand that is used as the trigger to activate the deoxyribonuclease activity of CRISPR/Cas12a for further signal amplification. The cleavage of the target-activated blocker probe allows the methylene blue-labeled reporter probes to be captured by the reduced graphene oxide-modified electrode, leading to an obviously increased electrochemical signal. We only need to simply tune the sequence for target recognition in RCA components, and this strategy can be flexibly applied to the highly sensitive and specific detection of microRNAs, Parvovirus B19 DNA, and adenosine-5'-triphosphate and the calculated limit of detection is 0.83 aM, 0.52 aM, and 0.46 pM, respectively. In addition, we construct DNA logic circuits (YES, NOT, OR, AND) of DNA inputs to experimentally demonstrate the modularity and programmability of the stimuli-responsive RCA-CRISPR/Cas12a system. This work broadens the application of the CRISPR/Cas12a system to the immobilization-free electrochemical biosensing platform and provides a new thinking for developing a robust tool for clinical diagnosis.

Melatonin attenuates repeated mild traumatic brain injury-induced cognitive deficits by inhibiting astrocyte reactivation.

Melatonin has been well documented for its neuroprotective role through inhibiting oxidative stress against traumatic brain injury (TBI). However, the specific role of melatonin and the exact effects on cell responses (neurons, astrocytes, and microglia) in different brain regions are unclear. Here, we subjected mice to closed head injury, to establish a repeated mild TBI model and detect neuronal activity and glial responses in cognition-related brain regions after melatonin administration. Melatonin only showed cognitive enhancement if administered during early pathological stages, but not in late (chronic) stages. Additionally, we observed a significant increase in neuronal activity and inhibition of astrocyte reactivation in medial prefrontal cortex and hippocampus, but not in other cognitive deficit related brain regions. Furthermore, by activating astrocytes in these brain regions, we found neuronal activity upregulation and cognitive improvement following melatonin treatment. Therefore, we concluded that melatonin administration during the early stages of TBI is necessary to inhibit astrocyte reactivation and to promote cognitive function. Our results provide evidence for use of melatonin for cognitive improvement after TBIs.

Design, Synthesis, Antibacterial, Antifungal and Anticancer Evaluations of Novel ß-Pinene Quaternary Ammonium Salts.

ß-pinene is a monoterpene isolated from turpentine oil and numerous other plants' essential oils, which has a broad spectrum of biological activities. In the current work, six novel ß-pinene quaternary ammonium (ß-PQA) salts were synthesized and evaluated in vitro for their antifungal, antibacterial and anticancer activities. The in vitro assay results revealed that compounds 4a and 4b presented remarkable antimicrobial activity against the tested fungi and bacteria. In particular, compound 4a showed excellent activities against F. oxysporum f.sp. niveum, P. nicotianae var.nicotianae, R. solani, D. pinea and Fusicoccumaesculi, with EC50 values of 4.50, 10.92, 9.45, 10.82 and 6.34 µg/mL, respectively. Moreover, compound 4a showed the best antibacterial action against E. coli, P. aeruginosa, S. aureus and B. subtilis, with MIC at 2.5, 0.625, 1.25 and 1.25 µg/mL, respectively. The anticancer activity results demonstrated that compounds 4a, 4b, 4c and 4f exhibited remarkable activity against HCT-116 and MCF-7 cell lines, with IC50 values ranged from 1.10 to 25.54 µM. Notably, the compound 4c displayed the strongest cytotoxicity against HCT-116 and MCF-7 cell lines, with the IC50 values of 1.10 and 2.46 µM, respectively. Furthermore, preliminary antimicrobial mechanistic studies revealed that compound 4a might cause mycelium abnormalities of microbial, cell membrane permeability changes and inhibition of the activity of ATP. Altogether, these findings open interesting perspectives to the application of ß-PQA salts as a novel leading structure for the development of effective antimicrobial and anticancer agents.

Daily Short Message Service Reminders Increase Treatment Compliance and Efficacy in Outpatients with Functional Dyspepsia: a Prospective Randomized Controlled Trial.

BACKGROUND: Many outpatients with functional dyspepsia (FD) do not follow the medication schedule recommendations, which can lead to illness relapse. OBJECTIVE: To investigate whether short message service (SMS) reminders improve medication regimen adherence and therapeutic efficacy in outpatients with FD. DESIGN: Participants with FD were randomly allocated to the control group or intervention group. Patients in the control group received a 4-week medication treatment with no reminders, those in the intervention group received medication treatment plus a daily SMS reminder of dose and medication time. PARTICIPANTS: Newly diagnosed FD patients from April 2019 to June 2019 were recruited from the GI outpatient clinics at Renji Hospital. MEASUREMENTS: The scores for FD symptoms (LDQ) and psychological conditions (PHQ-9 for depression and GAD-7 for anxiety) were assessed before and after the treatment. The medication possession ratio (MPR) was calculated. KEY RESULTS: A total of 352 eligible patients was enrolled in the study. The overall compliance rates of patients in the intervention and control groups were 87.5% and 80.7% in the intention-to-treat (ITT) analysis (P = 0.08) and 94.48% and 86.59% in per-protocol (PP) analysis (P = 0.015), respectively. In the intervention group, the compliance rate of younger patients (age ≤ 40 years) was significantly higher than that of age-matched patients in the control group (ITT: 86.1% vs. 70.5%, P = 0.018). Compared with the control group, the reduction in scores of LDQ (9.33 vs. 8.02, P = 0.017), PHQ-9 (6.97 vs. 5.69, P = 0.004), and GAD-7 (8.70 vs.7.53, P = 0.028) was significantly greater in patients receiving SMS reminders. The MPR of patients positively correlated with the reduction in scores of LDQ, PHQ-9, and GAD-7 in both groups. CONCLUSIONS: SMS reminders can improve treatment compliance and efficacy in patients with FD. TRIAL REGISTRATION: NCT04052750.

Microglial Trem2 induces synaptic impairment at early stage and prevents amyloidosis at late stage in APP/PS1 mice.

Triggering receptor expressed in myeloid cells (TREM)2 is a genetic high-risk factor for sporadic Alzheimer's disease (AD) and is considered a potential target for AD diagnosis and therapy, although its role in the different stages of AD remains controversial. We generated an embryonic deletion of Trem2 (whole body deletion) and induced hippocampal- and cortical-specific knockdown of microglial Trem2 at different stages of the AD process in amyloid precursor protein/Psen1 mice by adeno-associated virus (AAV) infection. AAV infection induced microglial Trem2 overexpression in the hippocampus of wild-type (WT) and thymus cell antigen 1-enhanced green fluorescent protein mice. Mice were subjected to ethological and pathologic tests. Whole body genetic deletion of Trem2 exerted different electrophysiological outcomes between different AD pathologic stages, which results from a complex integration of synaptic loss and amyloid aggregation. Interestingly, knockdown of Trem2 at the early-middle stage of AD (2-6 mo) prevents synaptic loss through directly inhibiting microglial phagocytosis, whereas knockdown of Trem2 at the middle-late stage of AD (6-10 mo) accelerates synaptic dysfunction because of more severe amyloid deposition caused by the depression of microglial phagocytosis. Additionally, hippocampal overexpression of Trem2 in WT mice results in significant synaptic impairment. Here, with transgenic technology and electrophysiological assay, we revealed that TREM2 up-regulation promotes microglial phagocytosis equally against synapse and amyloid plaques and eventually results in different outcomes. During the early-middle pathologic stage, TREM2 enhancing microglial phagocytosis mainly causes synaptic loss. However, TREM2 up-regulating microglial phagocytosis gradually supports a positive role when amyloid deposition occupies the leading position at the middle-late pathologic stage. In this study, we highlighted that TREM2 triggers synaptic loss during AD pathology development.-Sheng, L., Chen, M., Cai, K., Song, Y., Yu, D., Zhang, H., Xu, G. Microglial Trem2 induces synaptic impairment at early stage and prevents amyloidosis at late stage in APP/PS1 mice.

Bile acids induce visceral hypersensitivity via mucosal mast cell-to-nociceptor signaling that involves the farnesoid X receptor/nerve growth factor/transient receptor potential vanilloid 1 axis.

Increased colonic bile acid (BA) exposure, frequent in diarrhea-predominant irritable bowel syndrome (IBS-D), can affect gut function. Nerve growth factor (NGF) is implicated in the development of visceral hypersensitivity (VH). In this study, we tested the hypothesis that BAs cause VH via mucosal mast cell (MMC)-to-nociceptor signaling, which involves the farnesoid X receptor (FXR)/NGF/transient receptor potential vanilloid (TRPV)1 axis. BAs were intracolonically administered to rats for 15 d. Visceral sensitivity to colorectal distention and colonic NGF expression were examined. BAs caused VH, an effect that involved MMC-derived NGF and was accompanied by enhanced TRPV1 expression in the dorsal root ganglia. Anti-NGF treatment and TRPV1 antagonism inhibited BA-induced VH. BAs induced NGF mRNA and protein expression and release in cultured mast cells. Colonic supernatants from patients with IBS-D with elevated colonic BA content transcriptionally induced NGF expression. In FXR-/- mice, visceral sensitivity and colonic NGF expression were unaltered after BA treatment. Pharmacological antagonism and FXR silencing suppressed BA-induced NGF expression and release in mast cells. Mitogen-activated protein kinase kinase (MKK) 3/6/p38 MAPK/NF-κB signaling was mechanistically responsible for FXR-mediated NGF expression and secretion. The findings show an MMC-dependent and FXR-mediated pronociceptive effect of BAs and identify the BA/FXR/NGF/TRPV1 axis as a key player in MMC-to-neuron communication during pain processing in IBS.-Li, W.-T., Luo, Q.-Q., Wang, B., Chen, X., Yan, X.-J., Qiu, H.-Y., Chen, S.-L. Bile acids induce visceral hypersensitivity via mucosal mast cell-to-nociceptor signaling that involves the farnesoid X receptor/nerve growth factor/transient receptor potential vanilloid 1 axis.