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ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14183/m_MTBLS14183_LC-MS_alternating_reverse-phase_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14183/a_MTBLS14183_LC-MS_alternating_reverse-phase.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14183/s_MTBLS14183.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14183/i_Investigation.txtprimaryOK200ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14183The mass spectrometry data were processed using MultiQuant 3.0.3 software. Chromatographic peaks of the target compounds detected in different samples were integrated and calibrated based on the retention time and peak shape information of reference standards to ensure accurate qualitative and quantitative analysis. The figure below shows the quantitative integration and calibration results of a representative compound across different samples, with the x-axis representing retention time (min) and the y-axis representing ion intensity (cps).MetaboLightsPublicLiquid Chromatography MS - alternating - reverse-phaseThe LC analysis was performed on ACQUITY Liquid chromatography (Waters, USA). Mass spectrometric detection of metabolites was performed on AB5000 (AB SCIEX, USA). Gas chromatography conditions.ACQUITY UPLC BEH C18 column (2.1×100 mm, 1.7μm, Waters, USA) was used, the injection volume was 5μL, the column temperature was 40, and the mobile phase was A-0.01% formicacid water, B-acetonitrile. The gradient elution conditions were 0~4 min, 25% B; 4~9 min, 25~30% B; 9~14 min, 30~36% B; 14~18 min, 36~38% B; 18~24 min, 38~50% B; 24~32 min, 50~75% B; 32~33 min, 75~90% B; 33~35.5 min, 90~25% B. The flow rate was 0.25 mL/min.Gut microbiota-induced perturbations in bile acids alter keratinocyte lipid metabolism via FXR-NQO1 signaling in psoriasis.Duo KeaiPeking UniversitySerummass spectrometry assayPreparation of standard solutions.Weigh the bile acid standard and prepare it with methanol to make a final concentration of 1000μg/mL mixed standard stock solution, then dilute the stock solution with 30% methanol, and diluteit to ten standard. All stock solutions and working standard solutions were stored at freezer.Sample preparationSamples were extracted in 600 μL of methanol(-20) with 100 mg of glass beads, vortex for 60 s.Centrifuge at 12,000 rpm and 4 for 10 min, take 400 μL of the supernatant and concentrate it todryness with a vacuum concentrator. Add 100 μL of 30% methanol to reconstitute. Thesupernatant was filtered through 0.22μm membrane, and the filtrate was added to the LC-MSbottle.Mus musculusQuantitative analysis was performed using multiple reaction monitoring (MRM) on a triple quadrupole mass spectrometer. In MRM mode, the first quadrupole selects the precursor ions of the target compounds while excluding ions of other molecular weights to eliminate initial interference. The precursor ions are then fragmented in the collision cell via induced dissociation, generating multiple product ions. These product ions are subsequently filtered by the third quadrupole to select the desired characteristic fragment ions, excluding non-target ions and thereby ensuring high quantitative accuracy and reproducibility. After acquiring mass spectrometry data from different samples, the chromatographic peaks of all target compounds were integrated and quantified using standard curves.Groupkeaiduoduo998@126.comhttps://www.ebi.ac.uk/metabolights/MTBLS14183The psoriatic mouse model induced by imiquimod (IMQ) was induced on the shaved dorsal skin. In brief, the dorsal skin of each mouse was shaved 2 cm × 3 cm and then depilated until it was fully exposed. A total of 62.5 mg of 5% IMQ cream (Mingxinlidi, Sichuan) was applied to the exposed skin for 6 consecutive days. In parallel, the control mice were treated with Vaseline cream. On day 7, the serum samples were collected from mice for bile acids analysis.MetabolomicsGut microbiotaFXRMetabolomicsMus musculustargeted analysisPsoriasis70-1200KeratinocytesSerumWaters ACQUITY UPLC systemAB SCIEX QTRAP 6500Gut microbiotaFXRMetabolomicsMus musculustargeted analysisPsoriasis70-1200KeratinocytesSerumWaters ACQUITY UPLC systemAB SCIEX QTRAP 6500Electrospray ionization (ESI) source, negative ionization mode. The ion source temperature was 500, the ion source voltage was -4500 V, the collision gas was 6 psi, the curtain gas was 30 psi, and the atomizing gas and auxiliary gas were both 50 psi.Scans were performed using multiplereaction monitoring (MRM).falseGut microbiota-induced perturbations in bile acids alter keratinocyte lipid metabolism via FXR-NQO1 signaling in psoriasisEmerging evidence has shown that microbiota dysbiosis and aberrant bile acids (BAs) profiles are correlated with disease progression. This study elucidates dysregulated BAs metabolism in psoriasis patients and imiquimod-treated female mice, coupled with increased expression of the farnesoid X receptor (FXR) in keratinocytes. Activation of FXR by glycochenodeoxycholic acid (GCDCA) ameliorates psoriatic symptoms by enhancing lipid metabolism, particularly fatty acid oxidation. Mechanistically, the FXR-mediated enhancement of antioxidant capacity by upregulating NAD(P)H quinone dehydrogenase 1 (NQO1) expression underlies its regulatory role in lipid metabolism, offering an insight into FXR’s role in oxidative stress and lipid metabolism. Conversely, keratinocyte-specific FXR ablation exacerbates psoriasis severity. Gut microbiota dysbiosis is further identified as a pivotal contributor to perturbations in BA profiles in psoriasis. These findings support a mechanistic model linking gut microbiota and BA alterations to FXR signaling in keratinocytes and psoriasis-associated metabolic dysregulation, suggesting therapeutic potential for microbiota-targeted interventions.2026-03-292026-03-29MTBLS14183