One-Pot Three-Component Reaction for the Synthesis of 3,4-Dihydroquinazolines and Quinazolin-4(3H)-ones.

A highly efficient and straightforward one-pot synthesis of diversely substituted 3,4-dihydroquinazolines and quinazolin-4(3H)-ones has been achieved through a domino three-component assembly reaction of arenediazonium salts, nitriles, and bifunctional aniline derivatives. This new protocol involves three C-N bond formations through the initial formation of N-arylnitrilium intermediates from arenediazonium salts and nitriles, followed by the sequential nucleophilic addition and cyclization reactions with bifunctional anilines, leading to such N-heterocyclic compounds of biological and pharmacological importance. This method offers a simple, expedient, and robust approach with the use of amenable and easily accessible reactants/reagents under metal-free mild conditions, good functional group tolerance, and high efficiency. The synthetic applications were also demonstrated by derivatization of the products obtained from these processes and syntheses of a diverse range of valuable polycyclic N-heterocycles.

TRMT13 inhibits the growth of papillary thyroid cancer by targeting ANAPC4.

The recently discovered gene TRMT13 encodes a type of RNA methylase and is a member of the CCDC family (also called CCDC76). Here, we delineate its role in papillary thyroid cancer (PTC). Bioinformatics analysis shows significant TRMT13 and ANAPC4 downregulation in PTC and reveals that the expression levels of both genes are linearly correlated. Subsequent analyses confirm that both TRMT13 and ANAPC4 expressions are downregulated in PTC tissues and that this change in expression has a significant impact on cancer diagnosis. We conduct assays on PTC cells subjected to TRMT13 and ANAPC4 silencing or overexpression to assess the biological effects of these genes. We also perform rescue experiments to validate the regulatory effects of TRMT13 on ANAPC4. A nude mouse tumor model is used to evaluate the effects of TRMT13 and ANAPC4 on PTC tumorigenesis. TRMT13 expression is decreased in PTC tissues and cell lines and is positively correlated with that of ANAPC4. Cell assays reveal that TRMT13/ANAPC4 attenuates the malignancy of PTC cells by restraining cell proliferation, migration and invasion, while rescue experiments corroborate that ANAPC4 is a downstream target of TRMT13. In the nude mouse xenograft model, both TRMT13 and ANAPC4 inhibit tumor growth, and TRMT13 and ANAPC4 expression levels are significantly associated with survival. Taken together, these findings lead to the conclusion that TRMT13 inhibits PTC growth via ANAPC4, indicating a new role of TRMT13 and providing insights into the tRNA methyltransferase and coiled-coil domain-containing protein families.

Effects of a new magnetostrictive ultrasonic scaler and a traditional piezoelectric ultrasonic scaler on root surfaces and patient complaints.

Tooth wear and pain are the primary concerns of patients undergoing periodontal scaling. The aims of this study were to compare the effects of a new magnetostrictive ultrasonic scaler and a traditional piezoelectric ultrasonic scaler on tooth surface roughness and calculus removal and to determine their impacts on patient discomfort during supragingival cleaning. This article had two parts: an in vitro study and a clinical study. In the in vitro study, thirty teeth with subgingival calculus were randomly assigned to two scaling treatment groups: magnetostrictive scalers (n = 15) and piezoelectric scalers (n = 15). Surface roughness measurements were taken at baseline and after scaling, and the root samples were visualised by SEM after scaling. Additionally, a single-centre randomised split-mouth clinical trial was conducted. Eighty-five participants diagnosed with chronic gingivitis or periodontitis were randomly assigned to receive supragingival scaling. The magnetostrictive scaler was used in half of the mouths (n = 85), and the piezoelectric scaler was used in the other half of the mouths (n = 85). Data on pain, noise, and vibration were collected using a VAS questionnaire, and the operating time was recorded. In both in vitro and clinical studies, magnetostrictive scalers were reported to be more effective than piezoelectric scalers in removing dental deposits (P < 0.05). Additionally, the root surface after scaling with the magnetostrictive scaler was smoother than that after scaling with the piezoelectric scaler in the in vitro study (P = 0.02). SEM examination also revealed that fewer dental materials were lost after instrumentation with the magnetostrictive scaler than after instrumentation with the piezoelectric scaler. Piezoelectric scalers caused less discomfort to patients in terms of pain, noise, and vibration than magnetostrictive scalers (P < 0.05). According to this clinical study, the magnetostrictive scaler caused more discomfort during supragingival scaling than the piezoelectric scaler. Moreover, the magnetostrictive scaler was also more efficient and produced a smoother root surface with less material loss after scaling than the piezoelectric scaler, as demonstrated in the in vitro study.

Mesoporous nanoperforators as membranolytic agents via nano- and molecular-scale multi-patterning.

Plasma membrane lysis is an effective anticancer strategy, which mostly relying on soluble molecular membranolytic agents. However, nanomaterial-based membranolytic agents has been largely unexplored. Herein, we introduce a mesoporous membranolytic nanoperforators (MLNPs) via a nano- and molecular-scale multi-patterning strategy, featuring a spiky surface topography (nanoscale patterning) and molecular-level periodicity in the spikes with a benzene-bridged organosilica composition (molecular-scale patterning), which cooperatively endow an intrinsic membranolytic activity. Computational modelling reveals a nanospike-mediated multivalent perforation behaviour, i.e., multiple spikes induce nonlinearly enlarged membrane pores compared to a single spike, and that benzene groups aligned parallelly to a phospholipid molecule show considerably higher binding energy than other alignments, underpinning the importance of molecular ordering in phospholipid extraction for membranolysis. Finally, the antitumour activity of MLNPs is demonstrated in female Balb/c mouse models. This work demonstrates assembly of organosilica based bioactive nanostructures, enabling new understandings on nano-/molecular patterns co-governed nano-bio interaction.

HACE1 expression in heart failure patients might promote mitochondrial oxidative stress and ferroptosis by targeting NRF2.

BACKGROUND: Heart failure is a prevalent and life-threatening medical condition characterized by abnormal atrial electrical activity, contributing to a higher risk of ischemic stroke. Atrial remodelling, driven by oxidative stress and structural changes, plays a central role in heart failure progression. Recent studies suggest that HACE1, a regulatory gene, may be involved in cardiac protection against heart failure. METHODS: Clinical data analysis involved heart failure patients, while an animal model utilized C57BL/6J mice. RT-PCR, microarray analysis, histological examination, ELISA, and Western blot assays were employed to assess gene and protein expression, oxidative stress, and cardiac function. Cell transfection and culture of mouse atrial fibroblasts were performed for in-vitro experiments. RESULTS: HACE1 expression was reduced in heart failure patients and correlated negatively with collagen levels. In mouse models, HACE1 up-regulation reduced oxidative stress, mitigated fibrosis, and improved cardiac function. Conversely, HACE1 knockdown exacerbated oxidative stress, fibrosis, and cardiac dysfunction. HACE1 also protected against ferroptosis and mitochondrial damage. NRF2, a transcription factor implicated in oxidative stress, was identified as a target of HACE1, with HACE1 promoting NRF2 activity through ubiquitination. CONCLUSIONS: HACE1 emerges as a potential therapeutic target and diagnostic marker for heart failure. It regulates oxidative stress, mitigates cardiac fibrosis, and protects against ferroptosis and mitochondrial damage. The study reveals that HACE1 achieves these effects, at least in part, through NRF2 activation via ubiquitination, offering insights into novel mechanisms for heart failure pathogenesis and potential interventions.

Anomalous spin current anisotropy in a noncollinear antiferromagnet.

Cubic materials host high crystal symmetry and hence are not expected to support anisotropy in transport phenomena. In contrast to this common expectation, here we report an anomalous anisotropy of spin current can emerge in the (001) film of Mn3Pt, a noncollinear antiferromagnetic spin source with face-centered cubic structure. Such spin current anisotropy originates from the intertwined time reversal-odd ([Formula: see text]-odd) and time reversal-even ([Formula: see text]-even) spin Hall effects. Based on symmetry analyses and experimental characterizations of the current-induced spin torques in Mn3Pt-based heterostructures, we find that the spin current generated by Mn3Pt (001) exhibits exotic dependences on the current direction for all the spin components, deviating from that in conventional cubic systems. We also demonstrate that such an anisotropic spin current can be used to realize low-power spintronic applications such as the efficient field-free switching of the perpendicular magnetizations.

Spatially Resolved Organic Whispering-Gallery-Mode Hetero-Microrings for High-Security Photonic Barcodes.

Whispering-gallery-mode (WGM) microcavities featuring distinguishable sharp peaks in a broadband exhibit enormous advantages in the field of miniaturized photonic barcodes. However, such kind of barcodes developed hitherto are primarily based on microcavities wherein multiple gain medias were blended into a single matrix, thus resulting in the limited and indistinguishable coding elements. Here, a surface tension assisted heterogeneous assembly strategy is proposed to construct the spatially resolved WGM hetero-microrings with multiple spatial colors along its circular direction. Through precisely regulating the charge-transfer (CT) strength, full-color microrings covering the entire visible range were effectively acquired, which exhibit a series of sharp and recognizable peaks and allow for the effective construction of high-quality photonic barcodes. Notably, the spatially resolved WGM hetero-microrings with multiple coding elements were finally acquired through heterogeneous nucleation and growth controlled by the directional diffusion between the hetero-emulsion droplets, thus remarkably promoting the security strength and coding capacity of the barcodes. The results would be useful to fabricate new types of organic hierarchical hybrid WGM heterostructures for optical information recording and security labels.

The expression and distribution of TACAN in human and rat bladders.

OBJECTIVES: A lot of ion channels participate in the regulation of bladder function. TACAN, a new mechanosensitive ion channel, was first discovered in 2020. TACAN has been found to be expressed in many tissues, such as the dorsal root ganglia (DRG) and adipose tissue. However, it is unclear whether or not TACAN is expressed in the bladder. In this work, we decided to study the expression and distribution of TACAN in human and rat bladders. Meanwhile, the expression of TACAN in the rat model of interstitial cystitis/bladder pain syndrome (IC/BPS) was studied. METHODS: Human bladder tissues were obtained from female patients. Cyclophosphamide (CYP) was used to build the rat model of IC/BPS. Real-time polymerase chain reaction, agarose gel electrophoresis, and western blotting were used to assess the expression of TACAN in human and rat bladders. Immunohistochemistry and immunofluorescence were used to observe the distribution of TACAN in human and rat bladders. Hematoxylin-eosin stain, withdrawal threshold, and micturition interval were used to evaluate animal models. RESULTS: The results of agarose gel electrophoresis and western blotting suggested that TACAN was expressed in human and rat bladders. Immunohistochemical results suggested that TACAN showed positive immunoreaction in the urothelial and detrusor layers. The immunofluorescence results indicated that TACAN was co-stained with UPKIII, α-SMA, and PGP9.5. The IC/BPS model was successfully established with CYP. The mRNA and protein expression of TACAN was upregulated in the CYP-induced rat model of IC/BPS. CONCLUSIONS: TACAN was found in human and rat bladders. TACAN was mainly distributed in the urothelial and detrusor layers and bladder nerves. The expression of TACAN was upregulated in the CYP-induced rat model of IC/BPS. This new discovery will provide a theoretical basis for future research on the function of TACAN in the bladder and a potential therapeutic target for IC/BPS.

Analytical performances of a new rapid assay of soluble ST2 for cardiac and inflammatory diseases and establishment of the reference intervals for children and adolescence in China.

Background: sST2 has emerged as a potential disease biomarker of cardiac and inflammatory diseases in pediatrics. This study aimed to evaluate the performance of the new Pylon sST2 assay and establish the reference intervals of sST2 in children and adolescence in China. Methods: The experiments on precision, linearity, effects of interferents and sample stability were carried out to evaluate the analytical performances. A total of 240 healthy participants, aged from 2 to 17 years were enrolled. The nonparametric method was used to calculate the age- and sex-specified reference intervals. sST2 levels were measured in children with different diseases to evaluate the assay's diagnostic performance. Results: The repeatability and within-laboratory imprecision CVs of the assay were 6.0% and 7.6% at 19.5 ng/ml, and 3.1% and 5.9% at 289.8 ng/ml, respectively. The method showed linearity between 2.5 and 918.5 ng/ml. It was also noteworthy that the sST2 level was not affected in the presence of hemoglobin (2 mg/ml), triglyceride (30 mg/ml), bilirubin (0.3 mg/ml) and cholesterol (5 mg/ml). sST2 was found stable for 5 days at 4 °C in serum sample. The reference interval was determined as 2.1-21.0 ng/ml in general. No significant variation was observed by sex. However, sST2 increased constantly with age, especially in male. Increased sST2 was found in patients of systemic lupus erythematosus, sepsis, Crohn's diseases, respiratory failure and post cardiac surgery. Conclusions: The Pylon sST2 assay showed good analytical performances. The reference intervals were established in children and adolescence and sST2 showed potential clinical values in several diseases in pediatrics.

Field-free spin-orbit torque switching in interlayer exchange coupled Co/Ta/CoTb.

This study investigates a T-type field-free spin-orbit torque device with an in-plane magnetic layer coupled to a perpendicular magnetic layer via a non-magnetic spacer. The device utilizes a Co/Ta/CoTb structure, in which the in-plane Co layer and the perpendicular CoTb layer are ferromagnetically (FM) coupled through the Ta spacer. 'T-type' refers to the magnetization arrangement in the FM/spacer/FIM structure, where the magnetization in FM is in-plane, while in FIM, it is out-of-plane. This configuration forms a T-shaped arrangement for the magnetization of the two magnetic layers. Additionally, 'interlayer exchange coupling (IEC)' denotes the interaction between the two magnetic layers, which is achieved by adjusting the material and thickness of the spacer. Our results show that an in-plane effective field from the IEC enables deterministic current-induced magnetization switching of the CoTb layer. The field-driven and the current-driven asymmetric domain wall motion are observed and characterized by magneto-optic Kerr effect measurements. The functionality of multistate synaptic plasticity is demonstrated by understanding the relationship between the anomalous Hall resistance and the applied current pulses, indicating the potential for the device in spintronic memory and neuromorphic computing.

Potent pan huACE2-dependent sarbecovirus neutralizing monoclonal antibodies isolated from a BNT162b2-vaccinated SARS survivor.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern such as Omicron hampered efforts in controlling the ongoing coronavirus disease 2019 pandemic due to their ability to escape neutralizing antibodies induced by vaccination or prior infection, highlighting the need to develop broad-spectrum vaccines and therapeutics. Most human monoclonal antibodies (mAbs) reported to date have not demonstrated true pan-sarbecovirus neutralizing breadth especially against animal sarbecoviruses. Here, we report the isolation and characterization of highly potent mAbs targeting the receptor binding domain (RBD) of huACE2-dependent sarbecovirus from a SARS-CoV survivor vaccinated with BNT162b2. Among the six mAbs identified, one (E7) showed better huACE2-dependent sarbecovirus neutralizing potency and breadth than any other mAbs reported to date. Mutagenesis and cryo-electron microscopy studies indicate that these mAbs have a unique RBD contact footprint and that E7 binds to a quaternary structure-dependent epitope.

Safety and Efficacy of Botulinum Toxin Type A in Children With Spastic Cerebral Palsy Aged <2 Years: A Systematic Review.

In this study, we reviewed the safety and efficacy of botulinum toxin type A (BoNT-A) injection with respect to motor development in children with spastic cerebral palsy aged <2 years. Randomized controlled trials of BoNT-A published between July 1993 and May 2021 were searched in PubMed, WANFANG, CNKI (Chinese National Knowledge Infrastructure), and Cochrane Library Central Register of Controlled Trials using keywords "Botulinum Toxin," "cerebral palsy," "nao xing tan huan," "nao tan," and "rou du du su." The 11-item PEDro Scale was used to rate the quality of all the identified studies. Twelve studies, involving 656 subjects, met the inclusion criteria, and of these, 2 involved patients aged <2 years. Treatment safety was assessed based on adverse event (AE) number and frequency, and efficacy was assessed based on spasticity, range of movement, and motor development. We observed that 3 self-limiting adverse events that were frequently reported included weakness, dysesthesia of the skin, and pain at the injection site. Moreover, there was a significant decrease in the incidence of spasticity and a notable improvement in the range of movement of BoNT-A-treated patients. Therefore, BoNT-A injection shows great safety and efficacy in the treatment of children with cerebral palsy aged <2 years.

Barcode-structured YAG:Ce/YAG:Ce,Mn ceramic phosphors for variable CCT and high CRI LED/LD lighting.

Ceramic phosphors are widely considered the next-generation phosphor material for white LED/LD lighting, and a wide spectrum is a key factor in improving the CRI of lighting sources. In this paper, a novel, to our knowledge, barcode-structured YAG:Ce/YAG:Ce,Mn ceramic phosphor was designed and fabricated. The lighting sources with the CRI value of 73.5 and 68.9 were obtained under the excitation of blue LEDs and blue LDs, respectively. Simultaneously, thanks to the effective supplementary emission from a red LD, the CRI of the ceramic-based lighting source reached 81.8 under blue LD excitation. Specifically, the microstructure and luminescent property of ceramic phosphors with different thicknesses and ion doping concentrations were systematically studied. Besides, by changing the blue power from 0.52 W to 2.60 W, the CCT of the laser lighting source with the encapsulation of optimized YAG:Ce/YAG:Ce,Mn ceramic phosphors ranged from 3928 K to 5895 K, while the CRI always maintained above 80. The above results indicate that barcode-structured Ce:YAG/Ce,MnYAG ceramic phosphor is a candidate to achieve a high CRI and ican be applied to various lighting occasions.

Multiple myeloma identified within the same site of the mandible with medication-related osteonecrosis of jaw: An unusual case report.

RATIONALE: Multiple myeloma (MM) is a malignant disease characterized by abnormal proliferation of plasma cells, which usually occurs in middle-aged and elderly male patients. Bisphosphonates (BP) are commonly used for the treatment of MM bone disease. Long-time use of BP may cause medication-related osteonecrosis of the jaw (MRONJ). MRONJ occurs in jaw exclusively, and Multiple myeloma can also invade the jaw. The 2 diseases have similar clinical manifestations and imaging findings. This report present a case of MM identified in surgical specimen at the site that had been previously pathologically diagnosed as MRONJ in a patient with MM. PATIENT CONCERNS: A 57-years-old male patient visited our clinic on October 16, 2020 because of gingival swelling and pain in the right mandible for 1 month after extraction of the lower right premolar. The patient had a long-time illness history of multiple myeloma, and received intravenous zoledronic acid treatment. DIAGNOSES: Based on the clinical characteristics, imaging, and pathological findings of sequestrum formation and high inflammatory cell infiltration, the patient was diagnosed with MRONJ. After 1 year, a mandibular osteotomy was performed and pathological analysis showed the presence of necrotic bone and a large number of abnormal plasma cell infiltration, suggesting the presence of MM in the mandible. INTERVENTIONS: The patient was treated with a series of conservative treatments including antibiotic treatment, saline irrigation and laser irradiation, as well as superficial sequestration was. One year later, a mandibular osteotomy was performed. OUTCOMES: For the patient, the symptoms of gingival swelling, pain and discharge disappeared after surgery. LESSONS: These findings suggested MRONJ and MM could occur simultaneously at same site, so patients with MM presenting with symptoms of MRONJ should be screened for concurrent or disease relapse of multiple myeloma to prevent misdiagnosis or inadequate management. Meanwhile, this also suggests long-term inflammatory may lead to invasion of multiple myeloma.

Ganodermasides E-H, four new ergosterol derivatives from the endophytic fungus Epicoccum poae DJ-F associated with Euphorbia royleana.

Ganodermasides E-H (1-4), four new ergosterol derivatives and two known ones (5 and 6) were isolated from the fermentation of the endophytic fungus Epicoccum poae DJ-F in the stems of Euphorbia royleana Boiss. Their structures were elucidated by spectroscopic analysis, including extensive 1D NMR, 2D NMR, and HRESIMS techniques. All the isolated compounds were tested for their vitro antibacterial activity. Compounds 1-6 showed weak inhibitory effects on Staphylococcus epidermidis, Pseudomonas syringae, and Ralstonia solanacearum with MIC values ranging from 0.4 to 3.6 mM.

An Efficient Electrochemical Biosensor to Determine 1,5-Anhydroglucitol with Persimmon-Tannin-Reduced Graphene Oxide-PtPd Nanocomposites.

1,5-Anhydroglucitol (1,5-AG) is a sensitive biomarker for real-time detection of diabetes mellitus. In this study, an electrochemical biosensor to specifically detect 1,5-AG levels based on persimmon-tannin-reduced graphene oxide-PtPd nanocomposites (PT-rGO-PtPd NCs), which were modified onto the surface of a screen-printed carbon electrode (SPCE), was designed. The PT-rGO-PtPd NCs were prepared by using PT as the film-forming material and ascorbic acid as the reducing agent. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), ultraviolet-visible spectroscopy (UV-vis), and X-ray diffraction (XRD) spectroscopy analysis were used to characterise the newly synthesised materials. PT-rGO-PtPd NCs present a synergistic effect not only to increase the active surface area to bio-capture more targets, but also to exhibit electrocatalytic efficiency to catalyze the decomposition of hydrogen peroxide (H2O2). A sensitive layer is formed by pyranose oxidase (PROD) attached to the surface of PT-rGO-PtPd NC/SPCE. In the presence of 1,5-AG, PROD catalyzes the oxidization of 1,5-AG to generate 1,5-anhydrofuctose (1,5-AF) and H2O2 which can be decomposed into H2O under the synergistic catalysis of PT-rGO-PtPd NCs. The redox reaction between PT and its oxidative product (quinones, PTox) can be enhanced simultaneously by PT-rGO-PtPd NCs, and the current signal was recorded by the differential pulse voltammetry (DPV) method. Under optimal conditions, our biosensor shows a wide range (0.1-2.0 mg/mL) for 1,5-AG detection with a detection limit of 30 µg/mL (S/N = 3). Moreover, our electrochemical biosensor exhibits acceptable applicability with recoveries from 99.80 to 106.80%. In summary, our study provides an electrochemical method for the determination of 1,5-AG with simple procedures, lower costs, good reproducibility, and acceptable stability.

Impact of coronary artery disease on clinical outcomes after TAVR: Insights from the BRAVO-3 randomized trial.

OBJECTIVE: To determine the prognostic impact of coronary artery disease (CAD) in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR). BACKGROUND: CAD is a common comorbidity among patients undergoing TAVR and studies provide conflicting data on its prognostic impact. METHODS: The Bivalirudin on Aortic Valve Intervention Outcomes-3 (BRAVO-3) randomized trial compared the use of bivalirudin versus UFH in 802 high-surgical risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence or absence of history of CAD as well as periprocedural anticoagulation. The coprimary endpoints were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding) and major Bleeding Academic Research Consortium (BARC) bleeding ≥3b at 30 days postprocedure. RESULTS: Among 801 patients, 437 (54.6%) had history of CAD of whom 223 (51.0%) received bivalirudin. There were no significant differences in NACE (adjusted odds ratio [OR]: 1.04; 95% confidence interval [CI]: 0.69-1.58) or BARC ≥ 3b bleeding (adjusted OR: 0.84; 95% CI: 0.51-1.39) in patients with vs without CAD at 30 days. Among CAD patients, periprocedural use of bivalirudin was associated with similar NACE (OR: 0.80; 95% CI: 0.47-1.35) and BARC ≥ 3b bleeding (OR: 0.64; 95% CI: 0.33-1.25) compared with UFH, irrespective of history of CAD (p-interaction = 0.959 for NACE; p-interaction = 0.479 for major bleeding). CONCLUSION: CAD was not associated with a higher short-term risk of NACE or major bleeding after TAVR. Periprocedural anticoagulation with bivalirudin did not show any advantage over UFH in patients with and without CAD.

Lactobacillus rhamnosus MN-431 Metabolic Tryptophan Alleviates Complementary Food-Induced Diarrhea through PXR-NF-κB Pathway and AHR-Th17 Cell Response Pathways.

SCOPE: Lactobacillus rhamnosus MN-431 tryptophan broth culture (MN-431 TBC) can prevent complementary food-induced diarrhea (CFID). However, it is not clear whether this effect is related to indole derivatives. METHODS AND RESULTS: In this study, the anti-CFID effects of different components in MN-431 TBC including MN-431 cells, unfermented tryptophan broth, and supernatant of MN-431 TBC (MN-431 TBS) are investigated. Only MN-431 TBS can significantly prevent CFID, indicating that indole derivatives produced by MN-431 can exert antidiarrheal effects. Intestinal morphological analysis reveals that MN-431 TBS can increase the number of goblet cells, height of ileal villi, and length of rectal glands while also increasing the expression of ZO-1 in colon. Furthermore, HPLC analysis reveals the indole derivatives in MN-431 TBS are IAld and skatole. Cell experiments demonstrate that MN-431 TBS promotes the transcription of aryl hydrocarbon receptor (AHR) and pregnane X receptor (PXR), comparable to the synergistic effect of IAld and skatole. MN-431 TBS can activate AHR and reduces the concentrations of Th17 cell-inflammatory factors IL-17A and IL-21 in intestine and IL-17F, IL-21, and IL-22 in serum. MN-431 TBS can also activate PXR and reduces the concentrations of TNF-α and IL-6 in intestine and serum. CONCLUSION: MN-431 TBS, containing IAld and skatole, can exert anti-CFID effects through the AHR-Th17 and PXR-NF-κB pathways.