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1.
Food Chem ; 366: 130712, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34343953

RESUMO

The aim of this study was to investigate the effect of selenium enrichment on the gel properties and gastrointestinal digestive properties of egg white. Results of texture profile analysis, scanning electron microscopy and differential scanning calorimetry showed that the heat-induced gel of selenium-enriched egg white (EW-2) exhibited higher gel strength, smoother microstructure, and higher thermal denaturation temperature than ordinary egg white (EW-1), which might be due to the change of ovomucin and ovotransferrin content. The gastrointestinal digestive products of the EW-2 protein contained a higher proportion of small peptides and more free amino acids than those of EW-1. Results of oxygen radical absorbance capacity and cellular antioxidant activity assays indicated that digestive products of the EW-2 protein exhibited stronger antioxidant activity than those of the EW-1 protein. In summary, Se enrichment improved heat-induced gel properties of egg white, and promoted the gastrointestinal digestion of egg white protein.


Assuntos
Selênio , Animais , Galinhas , Digestão , Feminino , Temperatura Alta , Saccharomyces cerevisiae
2.
Behav Brain Res ; 416: 113540, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34419513

RESUMO

Dopamine (DA) transmission is important in the regulation of mood and anxiety behaviors. However, how specific dopaminergic signaling pathways respond to anxiogenic stimuli as well as regulate behaviors remains unknown. To understand how DA regulates the animal behaviors under anxiety we performed retrograde labeling and c-Fos staining of midbrain DA neurons. Our c-Fos labeling results showed that DA neurons projected to nucleus accumbens (NAc) are activated in animals treated with the elevated plus-maze (EPM). Real-time measurement of DA release using fast scanning cyclic voltammetry (FSCV) in NAc of freely behaving mice showed that increased DA release and more DA transients in the close arms than the open arms in the EPM. Meanwhile, we also observed a reduction of DA level from the close arms to the open arms. Local infusion of DA D1 receptor antagonist, SCH23390 in the core of NAc, leads to an anxiolytic-like effect in the open-field and EPM. These anxiolytic effects were not observed in animals received D2 receptor antagonist sulpiride infusion in the core of NAc. Taken together, our results reveal a novel function of the mesolimbic DA pathway through the D1 receptor in the regulation of anxiety-like behaviors.

3.
Eur J Pharmacol ; 911: 174526, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34599914

RESUMO

Berberine is an extract derived from Chinese herbs with pleiotropic cardiovascular protective effects. However, the underlying mechanism remains unclear because of its poor bioavailability. Herin, we aimed to investigate whether berberine affects choline diet-induced arterial thrombosis and explore the potential mechanism. Ultrasound and optical coherence tomography were used to assess the potential risk of artery thrombosis in vivo. The plasma concentrations of trimethylamine N-oxide (TMAO) and trimethylamine (TMA) were quantified with mass spectrometry. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) were utilized to detect the levels of microbial TMA-lyase choline utilization C (CutC) in faeces. Gut microbiota analysis was performed with 16S rRNA gene sequencing. For in vitro studies, platelet aggregometry, intracellular Ca2+ measurement, ATP release assay, flow cytometry and Western blot were applied to identify the effects of TMAO on platelets. Berberine treatment significantly decreased the CutC levels in the caecal contents, reduced choline diet-induced TMA and TMAO production, and subsequently, reduced the arterial thrombosis potential risk. Berberine administration remodelled the structure of gut microbiota in rats and increased the levels of the genus Lactobacillus. Finally, TMAO enhanced platelet reactivity to collagen by promoting the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2) and Jun N-terminal kinase (JNK) in platelets. These results demonstrate that berberine attenuates the risk of choline diet-induced arterial thrombosis by changing the gut microbial composition and reducing TMAO generation.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34636307

RESUMO

BACKGROUND: Sleep curtailment is a serious problem in many societies. Clinical evidence has shown that sleep deprivation is associated with mood dysregulation, formation of false memory, cardio-metabolic risk factors and outcomes, inflammatory disease risk, and all-cause mortality. The affective disorder dysregulation caused by insufficient sleep has become an increasingly serious health problem. However, to date, not much attention has been paid to the mild affective dysregulation caused by insufficient sleep, and there is no clear and standard therapeutic method to treat it. The Xiaoyao Pill is a classic Chinese medicinal formula, with the effect of dispersing stagnated hepatoqi, invigorating the spleen, and nourishing the blood. Therefore, it is most commonly used to treat gynecological diseases in China. In the present study, the effects of the Xiaoyao Pill on affective dysregulation of sleep-deprived mice and its underlying molecular mechanisms were investigated. METHODS: Forty adult female mice were used in the present study. The sleep deprivation model was established by improving the multi-platform water environment method. After 7 consecutive days of sleep deprivation, the mice were administrated low (LXYP, 0.32mg/kg) and high (HXYP, 0.64 mg/kg) doses of the Xiaoyao Pill for two weeks. Then, the body weight, behavioral deficits, and histopathology were evaluated. Meanwhile, the expression of c-fos protein and the concentrations of monoamine neurotransmitters in the hippocampus and prefrontal cortex were determined after two weeks of treatment. RESULTS: Xiaoyao Pill treatment significantly increased body weight and sucrose consumption and decreased the irritability scores of the sleep-deprived mice. Meanwhile, Xiaoyao Pill treatment prevented brain injury and inhibited the expression of c-fos protein in the hippocampus and prefrontal cortex. In addition, HXYP treatment significantly upregulated the levels of NE in the hippocampus and prefrontal cortex (p < 0.01). LXYP treatment significantly up-regulated the levels of 5-HT in the prefrontal cortex. Meanwhile, both HXYP and LXYP treatment significantly up-regulated the levels of DA in the prefrontal cortex (p < 0.05 or p < 0.01) of sleep-deprived mice. CONCLUSIONS: The present study demonstrates that Xiaoyao Pill treatment prevented the behavioral deficits of mice induced by sleep deprivation by promoting the recovery of brain tissue injury and up-regulating the levels of NE, 5-HT, and DA in the brain tissue.

5.
Pest Manag Sci ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34595835

RESUMO

BACKGROUND: The poultry red mite, Dermanyssus gallinae is recognized worldwide as the most important bloodsucking ectoparasite in layer and breeder flocks. In bloodsucking ectoparasites, ferritins (FERs), the iron-storage proteins, play a pivotal role in dealing with the challenge of large amounts of released iron during the digestion of blood meal. However, no information is available concerning FERs of D. gallinae. The aim of the present study was to investigate the characteristics, functions and the vaccine efficacy of FERs in D. gallinae. RESULTS: Two heavy-chain FERs of D. gallinae were identified and characterized. Phylogenetic analysis indicated that Dg-FER1 may be a secretory FER and Dg-FER2 as an intracellular one. RNAi results demonstrated that Dg-fers play key roles in mite survival, successful reproduction, and blood digestion. Immunization with rDg-FER1 or rDg-FER2 successfully induced chickens to produce high level of antigen-specific IgY, resulting in a significant increase in mite mortality (by 58.67% on day 5) and decreases in oviposition (by 42.15%) and fecundity (by 68.97%) in rDg-FER1 group, and a 13.73% increase in mite mortality and a 20.89% decrease in fecundity in the rDg-FER1 group. The overall immunization efficacy of rDg-FER1 was 93.51%. CONCLUSION: Two Dg-FERs are crucial to the survival, reproduction, and blood digestion of D. gallinae. This study has provided preliminary evidence demonstrating the potential of rDg-FER1 as a vaccine antigen for D. gallinae. This article is protected by copyright. All rights reserved.

6.
Nanoscale ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596199

RESUMO

Cesium tin halide (CsSnX3, where X is halogen) perovskite nanocrystals (NCs) are one of the most representative alternatives to their lead-based cousins. However, a fundamental understanding of how to regulate the growth kinetics of colloidal CsSnX3 NCs is still lacking and, specifically, the role of surfactants in affecting their growth kinetics remains incompletely understood. Here we report a general approach for colloidal synthesis of CsSnX3 perovskite NCs through a judicious combination of capping agents. We demonstrate that introducing a small amount of zwitterionic phosphatidylcholine in the reaction is of vital importance for regulating the growth kinetics of CsSnX3 NCs, which otherwise merely leads to the formation of large-sized powders. Based on a range of experimental characterization, we propose that the formation of intermediate complexes between zwitterionic phosphatidylcholine and the precursors and the steric hindrance effect of branched fatty acid side-chains of phosphatidylcholine can regulate the growth kinetics of CsSnX3, which enables us to obtain CsSnX3 NCs with emission quantum yields among the highest values ever reported. Our finding of using zwitterionic capping agents to regulate the growth kinetics may inspire more research on the synthesis of high-quality tin-based perovskite NCs that could speed up their practical applications in optoelectronic devices.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34596317

RESUMO

Production of multicarbon (C 2+ ) liquid fuels is a challenging task for electrocatalytic CO 2 reduction, mainly limited by the stabilization of reaction intermediates and their subsequent C-C couplings. In this work, we report a unique catalyst, the coordinatively unsaturated Cu sites on amorphous CuTi alloy (a-CuTi@Cu) toward electrocatalytic CO 2 reduction to multicarbon (C 2-4 ) liquid fuels. Remarkably, the electrocatalyst yields ethanol, acetone and n-butanol as major products with a total C 2-4 faradaic efficiency of about 49% at -0.8 V vs. reversible hydrogen electrode (RHE), which can be maintained for at least 3 months. Theoretical simulation together with in-situ characterization reveals that subsurface Ti atoms can increase the electron density of surface Cu sites and enhance the adsorption of *CO intermediate, which in turn reduces the energy barriers required for *CO dimerization and trimerization. This work refreshes the concept that the catalytically inactive element can maneuver the behaviour of catalytic sites in electrocatalytic C-C coupling from the angle of electron density.

8.
J Eukaryot Microbiol ; : e12872, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618995

RESUMO

Members of coccoid green algae have been documented in various extreme environments. In this article, a unicellular green alga was found to slowly grow in high concentration (3.6 g/L) and pure calcium chloride solution in the lab. It was successfully cultured and a taxonomic study combined approaches of morphological and molecular methods was conducted to determine its classification attribution, which was followed by a preliminary physiology research to explore its unique tolerance characteristics against calcium chloride stress. The strain was identified as Parachlorella kessleri by very similar morphology and the same phylogenetic position. The morphological differences among the three species in genus Parachlorella were then discussed and the characteristic traits of absent or thin mucilaginous envelop and mantel-shaped chloroplast for Parachlorella kessleri were supported. In addition, the almost strictly spherical shape of adult cells could further distinguish the Parachlorella kessleri from the other two species. The tolerant characteristics to CaCl2 stress for this strain were confirmed and the limit concentration was revealed as between 2,000 to 4,000 times than the standard BG11 culture concentration. Therefore, this Parachlorella kessleri strain is expected to be a good material to explore the mechanism of resistance to calcium ions stress for eukaryotic microbiology.

9.
Nucleic Acids Res ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648021

RESUMO

Single-cell RNA sequencing has become a powerful tool for identifying and characterizing cellular heterogeneity. One essential step to understanding cellular heterogeneity is determining cell identities. The widely used strategy predicts identities by projecting cells or cell clusters unidirectionally against a reference to find the best match. Here, we develop a bidirectional method, scMRMA, where a hierarchical reference guides iterative clustering and deep annotation with enhanced resolutions. Taking full advantage of the reference, scMRMA greatly improves the annotation accuracy. scMRMA achieved better performance than existing methods in four benchmark datasets and successfully revealed the expansion of CD8 T cell populations in squamous cell carcinoma after anti-PD-1 treatment.

10.
FASEB J ; 35(11): e21967, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34613630

RESUMO

To date, little attempt has been made to develop new treatments for Helicobacter pylori (H. pylori), although the community is aware of the shortage of treatments for H. pylori. In this study, we developed a 192-tandem-microwell-based high-throughput assay for ammonia that is a known virulence factor of H. pylori and a product of urease. We could identify few drugs, that is, panobinostat, dacinostat, ebselen, captan, and disulfiram, to potently inhibit the activity of ureases from bacterial or plant species. These inhibitors suppress the activity of urease via substrate-competitive or covalent-allosteric mechanism, but all except captan prevent the antibiotic-resistant H. pylori strain from killing human gastric cells, with a more pronounced effect than acetohydroxamic acid, a well-known urease inhibitor and clinically used drug for the treatment of bacterial infection. This study offers several bases for the development of new treatments for urease-containing pathogens and to study the mechanism responsible for the regulation of urease activity.

12.
Sci Rep ; 11(1): 20046, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625651

RESUMO

Radio frequency (RF) blackout occurs during radio attenuation measurement C (RAMC) vehicle reentry due to the attenuation effect of the plasma sheath on the communication signal. In recent years, the mitigation mechanism of chemical reaction for RF blackout problem has gradually been studied numerically and experimentally. However, the effect of non-ionization reaction rate has been ignored because it does not directly involve the generation of electrons. In the present study, the influence of non-ionizing reaction rate on the plasma generation mechanism and EM wave attenuation was numerically solved by the plasma flow and multilayer transmission model. According to the simulation results, only the reaction rate of [Formula: see text] has a significant effect on the electron number density in all non-ionizing reactions, and the degree of influence is less than the ionization reaction rate. The EM wave attenuation decreases with the decrease of the reaction rate of [Formula: see text]. When the reaction rate is reduced by 25 times, the maximum attenuation of electromagnetic wave can be reduced by 12 dB. Finally, a potential scheme by reducing the reaction rate of [Formula: see text] was proposed to mitigate the RF blackout problem.

13.
Chem Commun (Camb) ; 57(83): 10935-10938, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34596190

RESUMO

Herein we report a framework nucleic acid programmed strategy to develop nanocarriers to precisely and independently package multiple homo- and heterogeneous cargos in vitro and in vivo, thereby enabling multiplexed analysis of aptamer-ligand complexes to distinguish normal people and patients with prostate enlargement via simple serum tests, as well as favorable imaging and discrimination of MCF-7, PC-3 and A549 cancer cells and normal QSG-7701 cells.

14.
Cancer Med ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34668661

RESUMO

BACKGROUND: Secondary poor graft function (sPGF) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) related to poor outcome. We aimed to retrospectively evaluate the morbidity and hazard elements of sPGF after allo-HSCT. METHODS: Eight hundred and sixty-three patients who achieved initial engraftment of both neutrophils and platelets were retrospectively reviewed in this study. RESULTS: Fifty-two patients developed sPGF within 180 days post-transplants, with the median onset time was 62 days (range, 34-121 days) post-transplants. The overall cumulative incidence of sPGF within 180 days post-transplantation was 6.0%, with 3.4%, 3.4%, and 10.1%, respectively, in matched sibling donor (MSD), matched unrelated donor (MUD), and haploidentical donor (HID) transplant (p < 0.0001). Multivariable analysis showed that HID (HID vs. MSD: hazard ratio [HR] 2.525, p = 0.004; HID vs. MUD: [HR] 3.531, p = 0.017), acute graft versus host disease (aGVHD) within +30 days ([HR] 2.323, p = 0.003), and cytomegalovirus (CMV) reactivation ([HR] 8.915, p < 0.0001) within +30 days post-transplants were hazard elements of sPGF. The patients with sPGF had poorer survival than good graft function (51.7±8.1% vs. 62.9±1.9%, p < 0.0001). Our results also showed that only CMV reactivation was the hazard element for the development of PGF in HID transplant ([HR] 12.521 p < 0.0001). CONCLUSION: HID transplant is also an independent hazard element of sPGF except for aGVHD and CMV reactivation.

15.
Nano Lett ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34668713

RESUMO

Developing advanced electrode materials with enhanced charge-transfer kinetics is the key to realizing fast energy storage technologies. Commonly used modification strategies, such as nanoengineering and carbon coating, are mainly focused on electron transfer and bulk Li+ diffusion. Nonetheless, the desolvation behavior, which is considered as the rate-limiting process for charge-storage, is rarely studied. Herein, we designed a nitridation layer on the surface of Wadsley-Roth phase FeNb11O29 (FNO-x@N) to act as a desolvation promoter. Theoretical calculations demonstrate that the adsorption and desolvation of solvated Li+ is efficiently improved at FNO-x@N/electrolyte interphase, leading to the reduced desolvation energy barrier. Moreover, the nitridation layer can also help to prevent solvent cointercalation during Li+ insertion, leading to advantageous shrinkage of block area and reduced volume change of lattice cell during cycling. Consequently, FNO-x@N exhibits a high-rate capacity of 129.7 mAh g-1 with negligible capacity decay for 10 000 cycles.

16.
Immunol Res ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34669176

RESUMO

Immune thrombocytopenia (ITP) was defined using the International Consensus Guidelines as a platelet count <100×109/L in the absence of other causes or disorders that may be associated with thrombocytopenia. For patients without response to first-line treatment or refractory, TPO receptor agonist (RA) is an ideal choice. This study was to evaluate the efficiency and safety of eltrombopag for multi-line failed Chinese patients with immune thrombocytopenia (ITP) and analyze the possible factors that may contribute to the differences based on personal characteristics. Thirty-five multi-line failed ITP patients who received eltrombopag treatment were enrolled retrospectively at the First Affiliated Hospital of Zhejiang Chinese Medical University from January 2018 to August 2020. The general information, peripheral hemogram changes, count of bone marrow megakaryocyte (MK), peripheral T cell subsets were recorded, the response, and adverse effects, was evaluated. Results showed that the overall, complete, and partial response rates were 54.3% (n=19), 48.6% (n=17), and 5.7% (n=2) respectively to eltrombopag in our center. The overall response rate of patients with decreased MK was 70%, which was unexpectedly higher than that of the patient with increased or normal MK count (52.9% and 40%, respectively). For patients with poorer eltrombopag response group, more NK cells were found in peripheral blood, and the patient with decreased MK have a higher level of T helper (Th) cells and regulatory T (Treg) cells. Nine eltrombopag-related adverse events were reported, and most commonly were upper respiratory tract infection (8.6%), elevated alanine transaminase (ALT, 5.7%), and venous thrombosis (5.7%). In conclusion, this study revealed that ITP patients with decreased megakaryocyte respond well to eltrombopag, and the abnormality of NK cells may play a role in patients with a poor eltrombopag response.

17.
Sci Rep ; 11(1): 17759, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493746

RESUMO

Inducing cardiac myocytes to proliferate is considered a potential therapy to target heart disease, however, modulating cardiac myocyte proliferation has proven to be a technical challenge. The Hippo pathway is a kinase signaling cascade that regulates cell proliferation during the growth of the heart. Inhibition of the Hippo pathway increases the activation of the transcription factors YAP/TAZ, which translocate to the nucleus and upregulate transcription of pro-proliferative genes. The Hippo pathway regulates the proliferation of cancer cells, pluripotent stem cells, and epithelial cells through a cell-cell contact-dependent manner, however, it is unclear if cell density-dependent cell proliferation is a consistent feature in cardiac myocytes. Here, we used cultured human iPSC-derived cardiac myocytes (hiCMs) as a model system to investigate this concept. hiCMs have a comparable transcriptome to the immature cardiac myocytes that proliferate during heart development in vivo. Our data indicate that a dense syncytium of hiCMs can regain cell cycle activity and YAP expression and activity when plated sparsely or when density is reduced through wounding. We found that combining two small molecules, XMU-MP-1 and S1P, increased YAP activity and further enhanced proliferation of low-density hiCMs. Importantly, these compounds had no effect on hiCMs within a dense syncytium. These data add to a growing body of literature that link Hippo pathway regulation with cardiac myocyte proliferation and demonstrate that regulation is restricted to cells with reduced contact inhibition.

18.
Nanoscale ; 13(29): 12697-12710, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34477620

RESUMO

A small size effect could be conducive to enhancing the electrochemical performance, while the mechanism by which they also increase the capacitance for carbon electrode materials has not been established. Here, ultrasmall polyacrylonitrile particles with controllable sizes are supported on poly(ionic liquid)s microspheres (PILMs/PAN) by epitaxial polymerization growth strategy. Unlike traditional subtraction formulas in developing a porous architecture, we report on the synthesis of creating numerous micro/mesopores in carbon materials by addition theorem, and thus making for the perfection of packing density, which has not been reported yet. As an example, PILMC/PAN-L with a well-balanced specific surface area of 875.38 m2 g-1 and packing density of 1.05 g cm-3 demonstrated gravimetric and volumetric capacitances of 309 F g-1 and 324.45 F cm-3 at 0.5 A g-1, showing good rate performance and stable cyclability. Moreover, the underlying mechanism is thoroughly developed using multiple electrochemical methods. On this basis, this work would afford avenues to further enhancing the electrochemical performance, especially in exploring advanced carbon materials.

19.
Curr Drug Metab ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473615

RESUMO

BACKGROUND: Imatinib, sunitinib, and gefitinib are the three most common tyrosine kinase inhibitors (TKIs). However, their quantitative drug-drug interaction potentials In vivo and the relationship between their structure and inhibitory activity remain unknown. OBJECTIVE: This study aimed to investigate the potential drug-drug interaction risk of three TKIs based on CYP3A. METHODS: 6ß-Hydroxylated testosterone formation was selected to probe the CYP3A activity in human liver microsomes. Molecular docking simulation was performed to explore the potential structural alerts. RESULTS: Imatinib exhibited the strongest inhibitory effect towards CYP3A, while the inhibitory potential of gefitinib and sunitinib were comparable to each other but weaker than imatinib. IC50 shift assays demonstrated that the inhibitory potential of all three TKIs was significantly increased after a 30-min preincubation with NADPH. The KI and Kinact values of imatinib, sunitinib, and gefitinib were 3.75 µM and 0.055 min-1, 1.96 µM and 0.037 min-1, and 9.94 µM and 0.031 min-1, respectively. IVIVE results showed that there was a 1.3- to 43.1-fold increase in the AUC of CYP3A-metabolizing drugs in the presence of the TKIs. CONCLUSION: All three TKIs exhibited a typical irreversible inhibitory effect towards CYP3A. The presence of more N-heterocycles and the resulting better binding confirmation of imatinib may have been responsible for its stronger inhibitory effect than sunitinib and gefitinib. Therefore, caution should be taken when CYP3A-metabolizing drugs are co-administrated with imatinib, sunitinib, or gefitinib.

20.
Gut Microbes ; 13(1): 1972746, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34530693

RESUMO

Activation of the NOX4/NLRP3 inflammasome pathway has been associated with fibrosis in other organs. An imbalance in intestinal bacteria is an important driving factor of liver fibrosis through the liver-gut axis. This study aimed to explore whether the effect of ursolic acid (UA) on liver fibrosis was associated with the NOX4/NLRP3 inflammasome pathways and intestinal bacteria. Wild-type (WT), NLRP3-/-, and NOX4-/- mice and AP-treated mice were injected with CCI4 and treated with or without UA. The intestinal contents of the mice were collected and analyzed by 16S rRNA sequencing. UA alleviated liver fibrosis, which manifested as decreases in collagen deposition, liver injury, and the expression of fibrosis-related factors, and the expression of NOX4 and NLRP3 was significantly inhibited by UA treatment. Even after CCI4 injection, liver damage and fibrosis-related factors were significantly decreased in NLRP3-/-, NOX4-/-, and AP-treated mice. Importantly, the expression of NLRP3 was obviously inhibited in NOX4-/- and AP-treated mice. In addition, the diversity of intestinal bacteria and the abundance of probiotics in NLRP3-/- and NOX4-/- mice was significantly higher than those in WT mice, while the abundance of harmful bacteria in NLRP3-/- and NOX4-/- mice was significantly lower than that in WT mice. The NOX4/NLRP3 inflammasome pathway plays a crucial role in liver fibrosis and is closely associated with the beneficial effect of UA. The mechanism by which the NOX4/NLRP3 inflammasome pathway is involved in liver fibrosis may be associated with disordered intestinal bacteria.

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