Metabolic-dysfunction-associated steatohepatitis (MASH) remains a major health challenge. Herein, we identify sphingomyelin phosphodiesterase 3 (SMPD3) as a key driver of hepatic ceramide accumulation through increasing sphingomyelin hydrolysis at the cell membrane. Hepatocyte-specific Smpd3 gene disruption or pharmacological inhibition of SMPD3 alleviates MASH, whereas reintroducing SMPD3 reverses the resolution of MASH. Although healthy livers express low-level SMPD3, lipotoxicity-induced DNA damage suppresses sirtuin 1 (SIRT1), triggering an upregulation of SMPD3 during MASH. This disrupts membrane sphingomyelin-ceramide balance and promotes disease progression by enhancing caveolae-dependent lipid uptake and extracellular vesicle secretion from steatotic hepatocytes to exacerbate inflammation and fibrosis. Consequently, SMPD3 acts as a central hub integrating key MASH hallmarks. Notably, we discovered a bifunctional agent that simultaneously activates SIRT1 and inhibits SMPD3, which shows significant therapeutic potential in MASH treatment. These findings suggest that inhibition of hepatic SMPD3 restores membrane sphingolipid metabolism and holds great promise for developing novel MASH therapies.

Dietary fat reshapes host-microbiota interactions, yet the upstream events that mediate overnutrition-driven microbiome alterations and metabolic dysfunction remain unclear. Here we compared mouse models of diet-induced and genetic obesity using multi-omics to identify the colonic mucus niche as an early, diet-sensitive driver of metabolic dysfunction. Excessive dietary lipids impaired glutamine metabolism and redox homeostasis in goblet cells, thinning the mucus layer and depleting the mucus-adapted symbiont Akkermansia muciniphila while expanding the bile-acid-transforming bacterium Clostridium scindens. Altered bile acid composition along the enterohepatic axis activates FXR-PLIN2 signalling in the small intestine and increases fat absorption. In parallel, enterocytes upregulate the PPARα-dependent uptake pathway that supports luminal lipid entry. Supplementation with glutamine restored goblet cell function and the gut microbiota-derived bile acid pool, thereby reducing intestinal FXR activation and lipid uptake. These findings reveal that dietary fat impairs colonic goblet cell function and reshapes microbial bile acid metabolism, influencing small-intestinal fat absorption.

Laser 3D printing technology offers significant benefits in fabricating silicon carbide (SiC) ceramics, largely due to its support-free structure and simplified construction process. However, the produced green parts exhibit considerable porosity and decreased strength, rendering them susceptible to damage during powder removal and subsequent processing stages. This vulnerability significantly hinders the practical applications of laser 3D-printed SiC ceramics. This study introduced the use of epoxy resin-phenolic resin dual binders in the laser 3D printing of SiC ceramics, with the aim of improving the integrity and performance of both the green and debinded parts, as well as the final SiC ceramics. The highest strength of the SiC green part, with a 5 vol% addition of epoxy resin, reached 6.82 +/- 0.38 MPa, while the strength of the densified SiC ceramic was enhanced to 240 +/- 5 MPa.

Metabolic dysfunction-associated steatotic liver disease (MASLD) remains a prevalent condition with limited diagnostic and therapeutic options. This study aims to identify metabolic signatures of disease progression and develop non-invasive diagnostic models through three independent cohorts (including two cohorts confirmed by biopsy and one cohort confirmed by ultrasound) involving 293 participants for detecting significant fibrosis (≥F2) and mild to severe inflammatory activity (≥I2) using multiple machine learning techniques. The fibrosis panel shows area under the receiver operating characteristic curve (AUROC) of 0.928 (95% confidence interval [CI]: 0.835-0.978), 0.829 (0.732-0.902), and 0.806 (0.724-0.872) in the discovery cohort, validation cohort 1, and validation cohort 2, respectively, outperforming the fibrosis-4 index (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), non-alcoholic fatty liver disease fibrosis score (NFS), liver stiffness measurement (LSM), and combination of hoMa, Ast and CK18 (MACK-3). The inflammation panel achieves AUROCs of 0.894 (0.791-0.957) and 0.776 (0.673-0.859) in the discovery cohort and validation cohort 1, respectively. The key metabolites guanidinoacetic acid (GAA) and sebacic acid (SA) demonstrate therapeutic efficacy in mice. These validated panels provide accurate stratification of MASLD severity, and GAA/SA offer therapeutic potential, advancing both diagnosis and treatment strategies.

Ethnopharmacological relevance: Ulcerative colitis (UC), a chronic inflammatory bowel disease, has become a significant public health challenge due to the limited effectiveness of available therapies. Huoxiang Zhengqi (HXZQ), a well-established traditional Chinese formula, shows potential in managing UC, as suggested by clinical and pharmacological studies. However, the active components and mechanisms responsible for its effects remain unclear. Aim of study: This study aimed to identify the bioactive components of HXZQ responsible for its therapeutic effects on UC and to elucidate their underlying mechanisms. Materials and methods: The effect of HXZQ against dextran sodium sulfate (DSS)-induced colitis was investigated. Ingredients in HXZQ were characterized and analyzed in colitic mice using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). In vitro, biological activity of compounds was assessed using lipopolysaccharide (LPS)-induced Ana-1 cells and bone marrow-derived macrophages (BMDMs), tumor necrosis factor-alpha (TNF-alpha)-induced Caco-2 cells, and isolated intestinal crypts from colitic mice. These results were confirmed in vivo. The targets of the components were identified through bioinformatics analysis and validated via molecular docking, enzyme inhibition assays, and in vivo experiments. Hematoxylin and eosin (HE) staining, periodic acid-Schiff (PAS) staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative real-time polymerase chain reaction (qPCR) were employed to confirm the pharmaceutical effects. Results: A clinical equivalent dose of HXZQ (2.5 mL/kg) effectively treated DSS-induced colitis. A total of 113 compounds were identified in HXZQ, with 35 compounds detected in colitic mice. Glycyrrhizic acid (GA) and patchouli alcohol (PA) emerged as key contributors to the anti-colitic effects of HXZQ. Further investigation revealed that HXZQ and its active components decreased the levels of pro-inflammatory cytokines TNF-alpha, interleukin-1(3 (IL-1(3), and interleukin-6 (IL-6) in colon, likely by inhibiting nuclear factor kappa-B (NF-kappa B) signaling pathway. This inhibition indirectly activated the intestinal farnesoid X receptor (FXR) signaling pathway, correcting bile acid imbalances caused by colitis. Additionally, these components significantly enhanced the expression of tight junction proteins ZO-1 and Occludin, as well as the adhesion protein E-cadherin, and reduced goblet cell loss, thereby repairing intestinal barrier injury. Mechanistically, GA and PA were found to inhibit 11(3-hydroxysteroid dehydrogenase 1 (11(3-HSD1) activity, leading to increased local active corticosterone levels in the intestine to exert anti-inflammatory effects. Notably, the inhibition of 11(3-HSD1 with the selective inhibitor BVT2733 (BVT) ameliorated colitis in mice. Conclusions: HXZQ exhibits therapeutic effects on UC, primarily through GA and PA inhibiting 11(3-HSD1. This suggests new natural therapy approaches for UC and positions 11(3-HSD1 as a potential target for colitis treatment.

Background:Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease, affecting over 30 % of diabetes mellitus (DM) patients. Early detection of DKD in DM patients can enable timely preventive therapies, and potentially delay disease progression. Since the kidney relies on fatty acid oxidation for energy, dysregulated lipid metabolism has been implicated in proximal tubular cell damage and DKD pathogenesis. This study aimed to identify lipid alterations during DKD development and potential biomarkers differentiating DKD from DM. Methods:lipidomics analysis was performed on serum collected from 55 patients with DM, 21 with early DKD stage and 32 with advanced DKD, and 22 healthy subjects. Associations between lipids and DKD risk were evaluated by logistic regression. Results:Lipid profiling revealed elevated levels of certain lysophosphatidylethanolamines (LPEs), phosphatidylethanolamines (PEs), ceramides (Cers), and diacylglycerols (DAGs) in the DM-DKD transition, while most LPEs, lysophosphatidylcholines (LPCs), along with several monoacylglycerol (MAG) and triacylglycerols (TAGs), increased further from DKD-E to DKD-A. Logistic regression indicated positive associations between LPCs, LPEs, PEs, and DAGs with DKD risk, with most LPEs correlating significantly with urinary albumin-to-creatinine ratio (UACR) and inversely with estimated glomerular filtration rate (eGFR). A machine-learning-derived biomarker panel, Lipid9, consisting of LPC(18:2), LPC(20:5), LPE (16:0), LPE (18:0), LPE (18:1), LPE (24:0), PE (34:1), PE (34:2), and PE (36:2), accurately distinguished DKD (AUC: 0.78, 95 % CI 0.68-0.86) from DM. Incorporating two clinical indexes, serum creatinine and blood urea nitrogen, the Lipid9-SCB model further improved DKD detection (AUC: 0.83, 95 % CI 0.75-0.90) from DM, and was notably more sensitive for identifying DKD-E (AUC: 0.79, 95 % CI 0.67-0.91). Conclusion:This study deciphers the lipid signature in DKD progression, and suggests the Lipid9-SCB panel as a promising tool for early DKD detection in DM patients.

The disruption of the diurnal rhythm has been recognized as a significant contributing factor to metabolic dysregulation. The important role of gut microbiota and bile acid metabolism has attracted extensive attention. However, the function of the gut microbiota-bile acid axis in regulating the diurnal rhythms of metabolic homeostasis remains largely unknown. Herein, we aimed to investigate the interplay between rhythmicity of host metabolism and gut microbiota-bile acid axis, as well as to assess the impact of obesity on them. We found that high fat diet feeding and Leptin gene deficiency (ob/ob) significantly disturbed the rhythmic patterns of insulin sensitivity and serum total cholesterol levels. The bile acid profiling unveiled a conspicuous diurnal rhythm oscillation of ursodeoxycholic acid (UDCA) in lean mice, concomitant with fluctuations in insulin sensitivity, whereas it was absent in obese mice. The aforementioned diurnal rhythm oscillations were largely desynchronized by gut microbiota depletion, suggesting the indispensable role of gut microbiota in diurnal regulation of insulin sensitivity and bile acid metabolism. Consistently, 16S rRNA sequencing revealed that UDCA-associated bacteria exhibited diurnal rhythm oscillations that paralleled the fluctuation in insulin sensitivity. Collectively, the current study provides compelling evidence regarding the association between diurnal rhythm of insulin sensitivity and gut microbiota-bile acid axis. Moreover, we have elucidated the deleterious effects of obesity on gut microbiome-bile acid metabolism in both the genetic obesity model and the diet-induced obesity model.

Silicon carbide(SiC)ceramics are widely used in critical industries such as aerospace,nuclear energy,chemical processing,and semiconductor manufacturing due to their unique thermal and electrical properties coupled with excellent mechanical properties.Nevertheless,conventional forming methods often fall short when it comes to producing large-sized and complex components.Selective laser sintering(SLS)printing has the advantages of no support,high material utilization,high processing efficiency,etc.,endowing it suitable for the precise fabrication of ceramic structural components with complicated shape.Here,the particle grading approach was employed to systematically investigate the impacts of processes such as cold isostatic pressing(CIP),precursor impregnation pyrolysis(PIP),and the combination of CIP with PIP followed by solid-phase sintering at atmospheric pressure.The results revealed that the graded powders significantly enhanced both the bulk density and the flexural strength of the formed body by over 20％compared to non-graded systems.Relative density of the graded system after CIP and subsequent solid-phase sintering at atmospheric pressure was over 90％,confirming successful densification during sintering.In contrast,the non-graded sintered body only achieved a density of 89％.Implementation of the particle grading led to an increase in bulk density,and it was beneficial for achieving higher densification during sintering.Consequently,the flexural strength of the grading-sintered body was significantly improved,reaching 136.8 MPa—a gain of over 37％compared to the non-graded counterpart whose flexural strength was only 99.4 MPa.Meanwhile,high-density SiC ceramics could be achieved by repeating PIP for four cycles combined with solid-phase sintering of which SiC ceramics density was comparable to that of CIP compacts.However,the bulk density of solid-phase sintered body after four PIP cycles was only 2.29 g/cm3,which was accompanied by a flexural strength of 59.6 MPa.

Selective laser printing offers distinct advantages for fabricating large-scale and complex-shaped SiC ceramic components. However, the high porosity and low strength exhibited by SiC green bodies manufactured by selective laser printing necessitate an efficient heat treatment method to improve density and strength. This study presents an efficient technique for preparing SiC ceramics using selective laser printing coupled with precursor impregnation and pyrolysis (PIP) and liquid phase sintering (LPS). To enhance the density of the green body, a particle gradation technique was employed. Subsequently, a selective laser printing-powder, comprising SiC, Al2O3, Y2O3, and phenolic resin, was utilized to obtain a green body with a tailored microstructure. Following selective laser printing, SiC ceramics with flexural strength of 150 MPa and relative density of 98.2 % were produced by precursor impregnation and pyrolysis, followed by pressureless sintering. The outcomes of this study demonstrate a viable strategy for fabricating high-performance SiC ceramics via selective laser printing.

Selective laser printing is a unique additive manufacturing technology that plays an irreplaceable role in the modern industrial revolution. This report reviews the recent advances in direct selective laser printing on the powder beds of SiC, Al2O3, ZrO2, SiO2, and some of their composites. A comparison of direct selective laser printing of each ceramic is also presented, describing existing results, limitations, and prospective solutions. In addition, the technical challenges and effective strategies to address them are presented.

Objectives. To compare four DNA extraction methods for recovering bacterial DNA from mammalian faecal samples. Methods and Results. Three commercial kits from QIAamp, TIANamp, and MAGEN, together with the classic cetyltrimethylammonium bromide (CTAB) method, were evaluated for their performance in extracting bacterial DNA from the gut microbiota of five mammals, including humans (Homo sapiens), macaques (Macaca mulatta), dogs (Canis lupus familiaris), golden hamsters (Mesocricetus auratus), and mice (Mus musculus). First, we assessed the efficiency of the four methods based on DNA yield, purity, and integrity. Then, we investigated the impact of these methods on microbial composition and diversity and examined the relative abundance of dominant phyla bacteria based on 16S rRNA gene sequencing and real-time quantitative PCR. Our results showed that the CTAB method yielded relatively larger amounts of DNA, while the MAGEN kit yielded more Firmicutes DNA and reflected the true status of the microbiota more accurately. Conclusions. Of the four methods tested, the traditional CTAB method and commercial MAGEN kit accomplished the best performance in terms of DNA concentration and Firmicutes abundance across most of the tested species. As the CTAB method and MAGEN kit exhibited different advantages, we further tested and compared their DNA extraction performance on a defined microbiota comprising six strains from four dominant phyla to see which one better reflected the true status of the microbiota. In conclusion, the MAGEN kit was found to be superior to the CTAB method, as the testing results were closer to that of the defined microbiota.

Porous SiC ceramics are preferable materials for industrial applications such as hot gas filtration and microfiltration, some areas of fine filtration exist where complex structures of ceramic components are required. In this study, a novel method was employed for preparing high-flux ceramic membranes via selective laser printing. The powder used for laser printing is a laboratory-prepared polysiloxane powder, which can be pyrolyzed under relatively lower temperatures to obtain SiOC ceramic membranes. From the results of characterization and testing, the obtained ceramic membranes exhibited inimitable pore microstructure, high porosity, and outstanding filtering performance. Laser printing demonstrated good potential to be a strong candidate for the next generation of ceramic membrane fabrication technology.

The gut microbiota interacts with the host via production of various metabolites of dietary nutrients. Herein, we proposed the concept of the gut microbiota-derived core nutrient metabolome, which covers 43 metabolites in carbohydrate metabolism, glycolysis, tricarboxylic acid cycle and amino acid metabolism, and established a quantitative UPLC-Q/TOF-MS method through 3-nitrophenylhydrazine derivatization to investigate the influence of obesity on the gut microbiota in mice. All metabolites could be simultaneously analyzed via separation on a BEH C18 column within 18 min. The lower limits of quantification of most analytes were less than 1 μM. Validation results demonstrated suitability for the analysis of mouse fecal samples. The method was then applied to detect the gut microbiota-derived nutrient metabolome in the feces of high-fat diet induced obese (DIO) and ob/ob (leptin-deficient) mice, as well as obesity-prone (OP) and obesity-resistant (OR) mice. Compared to the control groups, there were 13, 23 and 10 differentially abundant metabolites detected in ob/ob, DIO and OP groups, respectively. Among them, amino acids including leucine, isoleucine, glycine, methionine, tyrosine and glutamine were co-downregulated in the obese or OP mice and exhibited inverse association with body weight. 16S rDNA analysis revealed that the genera Lactobacillus and Dubosiella were also inversely associated with body weight and positively correlated with fecal amino acids. Collectively, our work provides an effective and simplified method for simultaneous quantifying the gut microbiota-derived core nutrient metabolome in mouse feces, which could assist various future studies on host-microbiota metabolic interaction.

Renal interstitial fibrosis (RIF), a progressive process affecting the kidneys in chronic kidney disease (CKD), currently lacks an effective therapeutic intervention. Traditional Chinese medicine (TCM) has shown promise in reducing RIF and slowing CKD progression. In this study, we demonstrated the dose-dependent attenuation of RIF by Ootheca mantidis (SPX), a commonly prescribed TCM for CKD, in a mouse model of unilateral ureteral obstruction (UUO). RNA-sequencing analysis suggested that SPX treatment prominently downregulated apoptosis and inflammation-associated pathways, thereby inhibiting the fibrogenic signaling in the kidney. We further found that transplantation of fecal microbiota from SPX-treated mice conferred protection against renal injury and fibrosis through suppressing apoptosis in UUO mice, indicating that SPX ameliorated RIF via remodeling the gut microbiota and reducing apoptosis in the kidneys. Further functional exploration of the gut microbiota combined with fecal metabolomics revealed increased levels of some probiotics, including Akkermansia muciniphila (A. muciniphila), and modulations in glutamine-related amino acid metabolism in UUO mice treated with SPX. Subsequent colonization of A. muciniphila and supplementation with glutamine effectively mitigated cell apoptosis and RIF in UUO mice. Collectively, these findings unveil a functionally A. muciniphila- and glutamine-involved gut-renal axis that contributes to the action of SPX, and provide important clue for the therapeutic potential of SPX, A. muciniphila, and glutamine in combatting RIF.

Silicon carbide (SiC) ceramics, as a high-performance structural-functional integrated material, are widely used in aerospace, nuclear industry and braking system. However, the conventional fabrication methods can not meet the increasing demands for large-scale and complex-structured SiC ceramics, such as engine nozzles, flaps and turbine blades. Binder jetting (BJ) 3D printing technology can overcome the traditional obstacle and provide a novel manufacturing roadmap. Here, we adopted this technique via SiC particle grading, optimized the particle size ratio based on gradation theory, and studied the influence of BJ printing on properties of SiC green body and as-sintered ceramic. For the particle-graded green body after BJ printing, SiC ceramics with a maximum flexural strength of (16.70 +/- 0.53) MPa was obtained after one precursor impregnation and pyrolysis (PIP) treatment, whose flexural strength was improved by 116% as compared with that BJ printed from a median diameter of 20 mu m. SiC ceramics were further densified using liquid phase siliconization, with the density, flexural strength, elastic modulus, and fracture toughness reaching (2.655 +/- 0.001) g/cm(3), (285 +/- 30) MPa, (243 +/- 12) GPa, and (2.54 +/- 0.02) MPa center dot m(1/2), respectively. XRD results demonstrated that the sintered SiC ceramics were mainly composed of 3C structured-beta-SiC. All results show that high-performance SiC ceramic materials are innovatively prepared by an efficient and reliable method, based on the combined techniques of particle grading, BJ printing, PIP and liquid silicon infiltration.

Electrodeposition of biopolymer shows attractive development on fabricating novel functional materials and devices. ZnO quantum dots (QDs) have drawn increasing attention due to their environmentally friendly and non-toxic features, and good fluorescence properties. This work develops a method based on the coordination electrodeposition of sodium alginate to prepare ZnO QDs and ZnO QDs/sodium alginate nanocomposite films on electrodes. The method has many advantages such as the simple operation, the mild condition, the good controllability and the environmentally friendly process. Moreover, it allows a facile post-treatment for products to directly obtain the nanocomposite films of QDs and biopolymer on electrodes. In the method, sodium alginate was not only used as the electrodeposition biopolymer, but also served as the stabilizing agent for preparing ZnO QDs as well as the main ingredient in the resulting nanocomposite film. TEM observation shows that there are nanoparticles with a relatively uniform size in the nanocomposite film, and that the average size of these nanoparticles is 6.0 nm. The ZnO QDs/sodium alginate nanocomposite film shows a clear orange fluorescence under 365 tun UV light. The UV-Vis spectrum of the nanocomposite film has a clear absorption peak at 340 nm, which is attributed to the typical absorption peak of ZnO QDs. The photoluminescence spectrum of the nanocomposite film shows a clear emission peak at 550 nm, which agrees with the emission peak of ZnO QDs. The above spectral data both prove that there are ZnO QDs in the nanocomposite film. Furthermore, the ZnO QDs/sodium alginate nanocomposite film on the electrode can be applied to conduct electrochemical detection of K-3[Fe(CN)(6)] with a detection limit of 2.64 mu mol/L. By taking advantage of the fluorescence properties, the ZnO QDs/sodium alginate nanocomposite film can be used for fluorescence detection of Cu2+ ions. Therefore, this work provides a novel method for the preparation of ZnO QDs and construction of QDs/biopolymer nanocomposite films. The resulting ZnO QDs/sodium alginate nanocomposite film has promising applications in the fields of electrochemical detection and fluorescence detection. [GRAPHICS] .

Farnesoid X receptor (FXR) has emerged as a promising therapeutic target for nonalcoholic steatohepatitis (NASH) because of its tightly interwoven relationship with bile acid homeostasis, inflammation, fibrosis, and glucose and lipid metabolism. Evidence showed that intestinal FXR antagonism exhibited remarkable metabolic improvements in mice. Herein, we developed a series of betulinic acid derivatives as potent intestinal FXR antagonists, and F6 was identified as the most potent one with an IC50 at 2.1 μM. F6 selectively inhibited intestinal FXR signaling and ameliorated the hepatic steatosis, inflammation, and fibrosis in Gubra-amylin NASH (GAN) and high-fat with methionine and choline deficiency (HFMCD) diet-induced NASH models. The beneficial effects were achieved by direct antagonism of intestinal FXR and feedback activation of hepatic FXR, thereby decreasing ceramides and repressing inflammasome activation in the liver. Collectively, our work substantially supports F6 as a promising drug candidate against NASH and demonstrates that antagonism of intestinal FXR signaling is a practical strategy for treating metabolic diseases.

Objective: High intake of caffeoylquinic acid (CQA)-rich dietary supplements, such as green coffee bean extracts, offers health-promoting effects on maintaining metabolic homeostasis. Similar to many active herbal ingredients with high pharmacological activities but low bioavailability, CQA has been reported as a promising thermogenic agent with anti-obesity properties, which contrasts with its poor oral absorption. Intestinal tract is the first site of CQA exposure and gut microbes might react quickly to CQA. Thus, it is of interest to explore the role of gut microbiome and microbial metabolites in the beneficial effects of CQA on obesity-related disorders. Results: Oral CQA supplementation effectively enhanced energy expenditure by activating browning of adipose and thus ameliorated obesity-related metabolic dysfunctions in high fat diet-induced obese (DIO) mice. Here, 16S rRNA gene amplicon sequencing revealed that CQA treatment remodeled the gut microbiota to promote its anti-obesity actions, as confirmed by antibiotic treatment and fecal microbiota transplantation. CQA enriched the gut commensal species Limosilactobacillus reuteri (L. reuteri) and stimulated the production of short-chain fatty acids, especially propionate. Mono-colonization of L. reuteri or low-dose CQA treatment did not reduce adiposity in DIO mice, while their combination elicited an enhanced thermogenic response, indicating the synergistic effects of CQA and L. reuteri on obesity. Exogenous propionate supplementation mimicked the anti-obesity effects of CQA alone or when combined with L. reuteri, which was ablated by the monocarboxylate transporter (MCT) inhibitor 7ACC1 or MCT1 disruption in inguinal white adipose tissues to block propionate transport. Conclusions: Our data demonstrate a functional axis among L. reuteri, propionate, and beige fat tissue in the anti-obesity action of CQA through the regulation of thermogenesis. These findings provide mechanistic insights into the therapeutic use of herbal ingredients with poor bioavailability via their interaction with the gut microbiota.

Although disrupted bile acid (BA) homeostasis is implicated in inflammatory bowel disease (IBD), the role of hepatic BA metabolism in the pathogenesis of colitis is poorly understood. Here, we found that cholic acid (CA) levels were increased in patients and mice. Cytochrome P450 8B1 (CYP8B1), which synthesizes CA, was induced in livers of colitic mice. CA-treated or liver Cyp8b1-overexpressing mice developed more severe colitis with compromised repair of the mucosal barrier, whereas Cyp8b1-knockout mice were resistant to colitis. Mechanistically, CA inhibited peroxisome proliferator-activated receptor alpha (PPARα), resulting in impeded fatty acid oxidation (FAO) and impaired Lgr5+ intestinal stem cell (ISC) renewal. A PPARα agonist restored FAO and improved Lgr5+ ISC function. Activation of the farnesoid X receptor (FXR) suppressed liver CYP8B1 expression and ameliorated colitis in mice. This study reveals a connection between the hepatic CYP8B1-CA axis and colitis via regulating intestinal epithelial regeneration, suggesting that BA-based strategies might be beneficial in IBD treatment.

CuS nanoparticles (NPs) and CuS NPs/alginate nanocomposite films are prepared using a novel method based on the coordinated electrodeposition of alginate. This method exquisitely utilizes the coordination of alginate with Cu2+ ions to carry out the electrodeposition, and alginate as the stabilizer for CuS NPs and the major ingredient in the nanocomposite film. Thus, the method has many advantages such as facile operation, green route, mild conditions, and convenient post-treatment. After the electrodeposition, a smooth and homogeneous film has been electrodeposited on the anodic electrode. Transmission electron microscopy observation reveals that there are nanoparticles (the average size of 6.0 nm) in the electrodeposited film. The results from spectral analysis further confirm the existence of CuS NPs. The CuS NPs/alginate nanocomposite film modified electrode can be directly constructed by taking advantage of the electrodeposition, which shows the electrochemical detection capability towards H2O2 and hydroquinone. The CuS NPs/alginate nanocomposite film also possesses the colorimetric detection capability toward H2O2 and dopamine. Therefore, this study offers a green and convenient method for fabricating CuS NPs and nanocomposite films, which is promising for applications in functional nanocomposites and detection fields.