M2 macrophages secrete glutamate-containing extracellular vesicles to alleviate osteoporosis by reshaping osteoclast precursor fate.

Osteoclast precursors (OCPs) are thought to commit to osteoclast differentiation, which is accelerated by aging-related chronic inflammation, thereby leading to osteoporosis. However, whether the fate of OCPs can be reshaped to transition into other cell lineages is unknown. Here, we showed that M2 macrophage-derived extracellular vesicles (M2-EVs) could reprogram OCPs to downregulate osteoclast-specific gene expression and convert OCPs to M2 macrophage-like lineage cells, which reshaped the fate of OCPs by delivering the molecular metabolite glutamate. Upon delivery of glutamate, glutamine metabolism in OCPs was markedly enhanced, resulting in the increased production of α-ketoglutarate (αKG), which participates in Jmjd3-dependent epigenetic reprogramming, causing M2-like macrophage differentiation. Thus, we revealed a novel transformation of OCPs into M2-like macrophages via M2-EVs-initiated metabolic reprogramming and epigenetic modification. Our findings suggest that M2-EVs can reestablish the balance between osteoclasts and M2 macrophages, alleviate the symptoms of bone loss, and constitute a new approach for bone-targeted therapy to treat osteoporosis.

[Correlation between active component content and color of Atractylodes Lancea and A. chinensis based on color difference principle].

We explored the correlations between the color difference values [ΔL~*(lightness), Δa~*(red-green), Δb~*(yellow-blue)] and the content of four active components(including sesquiterpenoids and polyacetylenes) in the powder of Atractylodes lancea and A. chinensis, aiming to provide reference for the quality evaluation of Atractylodis Rhizoma and establish a qualitative model that can distinguish between A. lancea and A. chinensis based on the chromatic values. The tristimulus values(L~*, a~*, and b~*) of 23 batches of A. lancea and A. chinensis were measured by a color difference meter. The content of atractylenolide Ⅱ, ß-eudesmol, atractylodin, and atractylone in the 23 batches of samples were measured by high performance liquid chromatography(HPLC). Principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were performed to establish the qualitative models for distinguishing between A. lancea and A. chinensis. SPSS was employed to analyze the correlations between the tristimulus values and the content of the four index components. The results showed that the established PCA and PLS-DA models can divide the A. lancea and A. chinensis samples into two regions, and the tristimulus values of A. lancea and A. chinensis were positively correlated with the content of ß-eudesmol and atractylodin. Therefore, the PCA and PLS-DA models can successfully identify A. lancea and A. chinensis, and the appearance color can be used to quickly predict the internal quality of Atractylodis Rhizoma. This study provides a reference for the quality evaluation of Atractylodis Rhizoma and the modern research on the color of Chinese medicinal materials.

Effect of mutations across reverse transcriptase region on HBV replication and progression of liver diseases in Chinese patients.

It was known that mutations in the RT region were mainly related to nucleot(s)ide analogs resistance. Increasing studies indicated that RT mutations were related to advanced liver diseases (ALD) and had effects on HBV replication, but the distribution characteristics of mutations across RT region in the development of liver diseases and the effect of RT mutations on HBV replication were not fully clarified. HBV RT region was direct-sequenced in 1473 chronic HBV-infected patients. Mutation frequencies were analyzed to identify the specific mutations differing between groups classified by genotypes, loads of HBV DNA, or progression of liver diseases. In the range of rt145-rt290, rt145, rt221, rt222, rt267, and rt271 were the genotype-polymorphic sites, while rt238 was the genotype-specific sites. Mutations at rt163, rt173, rt180, rt181, rt184, rt191, rt199, and rt214 were more frequent among patients with C-genotype HBV, while those at rt220, rt225, rt226, rt269, and rt274 were more frequent among patients with B-genotype HBV. RtM204V/I could reduce the HBV DNA loads while rtQ/L267H/R could increase the HBV DNA loads. RtV214A/E/I (OR 3.94, 95% CI 1.09 to 14.26) was an independent risk factor for advanced liver diseases. In summary, the hotspots of mutations were different between B and C genotypes. Besides the effect on the S region, RT mutations had effects on HBV replication by other unknown ways. RtV214A/E/I was found to be an independent risk factor for ALD, suggesting that mutations at rt214 site could be used as a potential virological marker for the liver disease progression.

miR-200b-3p mitigates oxaliplatin resistance via targeting TUBB3 in colorectal cancer.

BACKGROUND: Numerous abnormally expressed miRs have been reported involved in oxaliplatin (L-OHP) resistance of colorectal cancer (CRC). The present study aimed to investigate whether miR-200b-3p could regulate L-OHP resistance via targeting TUBB3 in CRC cells. METHODS: L-OHP resistant HT29 and HCT116 cells were exposed to escalating concentrations of L-OHP up to 30 µm. The effect of miR-200b-3p on L-OHP resistant CRC cells was then evaluated using the cell counting kit-8 (CCK-8) assay. CRC cell apoptosis was detected using Annexin V-FITC/PI double staining. Bioinformatics algorithms and luciferase reporter assays were also performed to investigate whether TUBB3 was a direct target of miR-200b-3p. RESULTS: miR-200b-3p declined in L-OHP resistant CRC tissues and cell lines, and the overexpression of miR-200b-3p elevated the L-OHP sensitivity in L-OHP resistant HT29 and HCT116 cells. In addition, we determined the potential mechanisms underlying miR-200b-3p-mediated reversal of L-OHP resistance by mediating its downstream target TUBB3, and the overexpression of miR-200b-3p could induce migration and growth inhibition and apoptosis in L-OHP resistant HT29 and HCT116 cells by silencing ßIII-tubulin protein expression. However, the overexpression of TUBB3 reversed miR-200b-3p mimic-induced migration, as well as growth inhibition and apoptosis, in L-OHP resistant CRC cells. CONCLUSIONS: miR-200b-3p improved L-OHP resistance and induced growth inhibition and cell apoptosis in L-OHP resistant CRC cells, and the underlying mechanism was mediated, at least partially, through the suppression of ßIII-tubulin protein expression.

(-)-4-O-(4-O-ß-D-glucopyranosylcaffeoyl) Quinic Acid Inhibits the Function of Myeloid-Derived Suppressor Cells to Enhance the Efficacy of Anti-PD1 against Colon Cancer.

PURPOSE: Immunotherapy in the clinic has demonstrated its potential to control cancer through disinhibiting the immune system, especially for immune checkpoint inhibitors such as anti-programmed cell death protein 1/anti-programmed death-ligand 1 (anti-PD1/anti-PD-L1). However, although these new immunotherapies have resulted in durable clinical responses in various cancers, multiple mechanisms of immune resistance and suppression exist in tumors. One significant barrier to efficacy of anti-PD1 against colon cancer may be the recruitment of myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment. Here we demonstrated functional inhibition of G-MDSC with (-)-4-O-(4-O-ß-D-glucopyranosylcaffeoyl) quinic acid (QA), an inhibitor of PI3Kδ/γ, reshaped the tumor immune microenvironment and promoted cytotoxic T cell-mediated tumor regression, resultantly enhancing responses to anti-PD1 treatment in colon tumor model. METHODS: A syngeneic colon tumor mouse model was used to study the effects of QA on tumor immune microenvironment and its potential synergistic effects with anti-PD1 blockade. RESULTS: QA treatment inhibited G-MDSC function in the tumor tissue. Additionally, combination treatment induced CD8+ T lymphocyte-dependent tumor growth delay and prolonged survival time in colon cancer. CONCLUSIONS: Our results offered opportunities for new combination strategies using a selective small molecule PI3Kδ/γ inhibitor, to suppress MDSCs to enhance responses to immune checkpoint blockade in colon cancer.

General Oriented Formation of Carbon Nanotubes from Metal-Organic Frameworks.

Carbon nanotubes (CNTs) are of great interest for many potential applications because of their extraordinary electronic, mechanical and structural properties. However, issues of chaotic staking, high cost and high energy dissipation in the synthesis of CNTs remain to be resolved. Here we develop a facile, general and high-yield strategy for the oriented formation of CNTs from metal-organic frameworks (MOFs) through a low-temperature (as low as 430 °C) pyrolysis process. The selected MOF crystals act as a single precursor for both nanocatalysts and carbon sources. The key to the formation of CNTs is obtaining small nanocatalysts with high activity during the pyrolysis process. This method is successfully extended to obtain various oriented CNT-assembled architectures by modulating the corresponding MOFs, which further homogeneously incorporate heteroatoms into the CNTs. Specifically, nitrogen-doped CNT-assembled hollow structures exhibit excellent performances in both energy conversion and storage. On the basis of experimental analyses and density functional theory simulations, these superior performances are attributed to synergistic effects between ideal components and multilevel structures. Additionally, the appropriate graphitic N doping and the confined metal nanoparticles in CNTs both increase the densities of states near the Fermi level and reduce the work function, hence efficiently enhancing its oxygen reduction activity. The viable synthetic strategy and proposed mechanism will stimulate the rapid development of CNTs in frontier fields.

Solvent-Free Synthesis of Uniform MOF Shell-Derived Carbon Confined SnO2 /Co Nanocubes for Highly Reversible Lithium Storage.

Tin dioxide (SnO2 ) has attracted much attention in lithium-ion batteries (LIBs) due to its abundant source, low cost, and high theoretical capacity. However, the large volume variation, irreversible conversion reaction limit its further practical application in next-generation LIBs. Here, a novel solvent-free approach to construct uniform metal-organic framework (MOF) shell-derived carbon confined SnO2 /Co (SnO2 /Co@C) nanocubes via a two-step heat treatment is developed. In particular, MOF-coated CoSnO3 hollow nanocubes are for the first time synthesized as the intermediate product by an extremely simple thermal solid-phase reaction, which is further developed as a general strategy to successfully obtain other uniform MOF-coated metal oxides. The as-synthesized SnO2 /Co@C nanocubes, when tested as LIB anodes, exhibit a highly reversible discharge capacity of 800 mAh g-1 after 100 cycles at 200 mA g-1 and excellent cycling stability with a retained capacity of 400 mAh g-1 after 1800 cycles at 5 A g-1 . The experimental analyses demonstrate that these excellent performances are mainly ascribed to the delicate structure and a synergistic effect between Co and SnO2 . This facile synthetic approach will greatly contribute to the development of functional metal oxide-based and MOF-assisted nanostructures in many frontier applications.

Skeleton-derived extracellular vesicles in bone and whole-body aging: From mechanisms to potential applications.

The skeleton serves as a supportive and protective organ for the body. As individuals age, their bone tissue undergoes structural, cellular, and molecular changes, including the accumulation of senescent cells. Extracellular vesicles (EVs) play a crucial role in aging through the cellular secretome and have been found to induce or accelerate age-related dysfunction in bones and to contribute further via the circulatory system to the aging of phenotypes of other bodily systems. However, the extent of these effects and their underlying mechanisms remain unclear. Therefore, this paper attempts to give an overview of the current understanding of age-related alteration in EVs derived from bones. The role of EVs in mediating communications among bone-related cells and other body parts is discussed, and the significance of bones in the whole-body aging process is highlighted. Ultimately, it is hoped that gaining a clearer understanding of the relationship between EVs and aging mechanisms may serve as a basis for new treatment strategies for age-related degenerative diseases in the skeleton and other systems.

Effect of Heat Treatment Combined with TG Enzyme Cross-Linking on the Zein-Pea Protein Complex: Physicochemical and Gel Properties.

Plant proteins have the advantages of low cost and high yield, but they are still not comparable to animal proteins in processing due to factors such as gelation and solubility. How to enhance the processing performance of plant proteins by simple and green modification means has become a hot research topic nowadays. Based on the above problems, we studied the effect of gel induction on its properties. In this study, a pea protein-zein complex was prepared by the pH cycle method, and the effects of different induced gel methods on the gel properties of the complex protein were studied. The conclusions are as follows: All three gel induction methods can make the complex protein form a gel system, among which the gel strength of heat treatment and the TG enzyme-inducted group is the highest (372.84 g). Through the observation of the gel microstructure, the gel double network structure disappears and the structure becomes denser, which leads to a stronger water-binding state of the gel sample in the collaborative treatment group. In the simulated digestion experiment, heat treatment and enzyme-induced samples showed the best slow-release effect. This study provides a new method for the preparation of multi-vegetable protein gels and lays a theoretical foundation for their application in food processing.

Riboflavin-loaded soy protein isolate cold gel treated with combination of high intensity ultrasound and high hydrostatic pressure: Gel structure, physicochemical properties and gastrointestinal digestion fate.

Transglutaminase (TGase) was added to soy protein isolate (SPI) dispersion after the combination treatment of high intensity ultrasound (HIU) and high hydrostatic pressure (HHP) to catalyze the formation of cold gel, which was used to encapsulate riboflavin. The structure, physicochemical properties and in vitro digestion characteristics of riboflavin-loaded SPI cold gel were investigated. HIU-HHP combined treatment enhanced the strength, water retention, elastic property, thermal stability and protein denaturation degree of riboflavin-loaded SPI cold gels, and improved the gel network structure, resulting in a higher encapsulation efficiency of riboflavin and its chemical stability under heat and light treatment. HIU-HHP combined treatment reduced the erosion and swelling of SPI cold gel in simulated gastrointestinal fluid, and improved the sustained release effect of SPI gel on riboflavin by changing the digestion mode and rate of gel. In addition, HIU-HHP combined treated gels promoted the directional release of riboflavin in the simulated intestinal fluid, thereby improving its bioaccessibility, which was related to the secondary structure orderliness, tertiary conformation tightness and aggregation degree of protein during the gastrointestinal digestion. Therefore, HIU-HHP combined treatment technology had potential application value in improving the protection, sustained/controlled release and delivery of SPI cold gels for sensitive bioactive compounds.

Measurement of Carbon Dioxide Isotopes with Air-Lasing-Based Coherent Raman Spectroscopy.

Isotope detection is crucial for geological research, medical diagnostics, industrial production, and environmental monitoring. Various spectroscopic techniques are continually emerging for isotopic identification and accurate measurement. Herein, coherent Raman scattering (CRS) spectroscopy is developed for the quantitative detection of carbon dioxide isotopes, in which the N2+ air lasing coherently created in the interaction region is used as the probe. Benefiting from the narrow spectral width of air lasing, the Raman peaks of 12CO2 and 13CO2 can be well discerned, although their spectra partially overlap. The overlapped signals were proven to be the result of the coherent superposition of individual Raman signals. Based on that fact, a deconvolution algorithm was designed to retrieve the concentration ratio of the two isotopes. The relative error of the measurement is less than 6%. The CRS technique based on air lasing offers a potential approach for the quantitative characterization of molecular isotopes, especially in application scenarios of remote sensing or in situ detection.

Effect of Microwave Intermittent Drying on the Structural and Functional Properties of Zein in Corn Kernels.

Microwave intermittent drying was carried out on newly harvested corn kernels to study the effects of different microwave intermittent powers (900 W, 1800 W, 2700 W, and 3600 W) on the structural and functional properties of zein in corn kernels. The results showed that microwave drying could increase the thermal stability of zein in corn kernels. The solubility, emulsification activity index, and surface hydrophobicity increased under 1800 W drying power, which was due to the unfolding of the molecular structure caused by the increase in the content of irregular structure and the decrease in the value of particle size. At a drying power of 2700 W, there was a significant increase in grain size values and ß-sheet structure. This proves that at this time, the corn proteins in the kernels were subjected to the thermal effect generated by the higher microwave power, which simultaneously caused cross-linking and aggregation within the proteins to form molecular aggregates. The solubility, surface hydrophobicity, and other functional properties were reduced, while the emulsification stability was enhanced by the aggregates. The results of the study can provide a reference for the in-depth study of intermittent corn microwave drying on a wide range of applications of zein in corn kernels.

Activation of free fatty acid receptors, FFAR1 and FFAR4, ameliorates ulcerative colitis by promote fatty acid metabolism and mediate macrophage polarization.

OBJECTIVE: To investigate the mechanism of action of fatty acid receptors, FFAR1 and FFAR4, on ulcerative colitis (UC) through fatty acid metabolism and macrophage polarization. METHODS: Dextran sulfate sodium (DSS)-induced mouse model of UC mice was used to evaluate the efficacy of FFAR1 (GW9508) and FFAR4 (GSK137647) agonists by analyzing body weight, colon length, disease activity index (DAI), and histological scores. Real-time PCR and immunofluorescence analysis were performed to quantify the levels of fatty acid metabolizing enzymes and macrophage makers. FFA-induced lipid accumulation in RAW264.7 cells was visualized by Oil Red O staining analysis, and cells were collected to detect macrophage polarization by flow cytometry. RESULTS: The combination of GW9508 and GSK137647 significantly improved DSS-induced UC symptoms, caused recovery in colon length, and decreased histological injury. GW9508 + GSK137647 treatment upregulated the expressions of CD206, lipid oxidation enzyme (CPT-1α) and anti-inflammatory cytokines (IL-4, IL-10, IL-13) but downregulated those of CD86, lipogenic enzymes (ACC1, FASN, SCD1), and pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α). Combining the two agonists decreased FFA-induced lipid accumulation and increased CD206 expression in cell-based experiments. CONCLUSION: Activated FFAR1 and FFAR4 ameliorates DSS-induced UC by promoting fatty acid metabolism to reduce lipid accumulation and mediate M2 macrophage polarization.

Establishing Pinhole Deposition Mode of Zn via Scalable Monolayer Graphene Film.

The uneven texture evolution of Zn during electrodeposition would adversely impact upon the lifespan of aqueous Zn metal batteries. To address this issue, tremendous endeavors are made to induce Zn(002) orientational deposition employing graphene and its derivatives. Nevertheless, the effect of prototype graphene film over Zn deposition behavior has garnered less attention. Here, it is attempted to solve such a puzzle via utilizing transferred high-quality graphene film with controllable layer numbers in a scalable manner on a Zn foil. The multilayer graphene fails to facilitate a Zn epitaxial deposition, whereas the monolayer film with slight breakages steers a unique pinhole deposition mode. In-depth electrochemical measurements and theoretical simulations discover that the transferred graphene film not only acts as an armor to inhibit side reactions but also serves as a buffer layer to homogenize initial Zn nucleation and decrease Zn migration barrier, accordingly enabling a smooth deposition layer with closely stacked polycrystalline domains. As a result, both assembled symmetric and full cells manage to deliver satisfactory electrochemical performances. This study proposes a concept of "pinhole deposition" to dictate Zn electrodeposition and broadens the horizons of graphene-modified Zn anodes.

The interaction between the nervous system and the stomatognathic system: from development to diseases.

The crosstalk between the nerve and stomatognathic systems plays a more important role in organismal health than previously appreciated with the presence of emerging concept of the "brain-oral axis". A deeper understanding of the intricate interaction between the nervous system and the stomatognathic system is warranted, considering their significant developmental homology and anatomical proximity, and the more complex innervation of the jawbone compared to other skeletons. In this review, we provide an in-depth look at studies concerning neurodevelopment, craniofacial development, and congenital anomalies that occur when the two systems develop abnormally. It summarizes the cross-regulation between nerves and jawbones and the effects of various states of the jawbone on intrabony nerve distribution. Diseases closely related to both the nervous system and the stomatognathic system are divided into craniofacial diseases caused by neurological illnesses, and neurological diseases caused by an aberrant stomatognathic system. The two-way relationships between common diseases, such as periodontitis and neurodegenerative disorders, and depression and oral diseases were also discussed. This review provides valuable insights into novel strategies for neuro-skeletal tissue engineering and early prevention and treatment of orofacial and neurological diseases.

Pesticides as a risk factor for cognitive impairment: Natural substances are expected to become alternative measures to prevent and improve cognitive impairment.

Pesticides are the most effective way to control diseases, insects, weeds, and fungi. The central nervous system (CNS) is damaged by pesticide residues in various ways. By consulting relevant databases, the systemic relationships between the possible mechanisms of pesticides damage to the CNS causing cognitive impairment and related learning and memory pathways networks, as well as the structure-activity relationships between some natural substances (such as polyphenols and vitamins) and the improvement were summarized in this article. The mechanisms of cognitive impairment caused by pesticides are closely related. For example, oxidative stress, mitochondrial dysfunction, and neuroinflammation can constitute three feedback loops that interact and restrict each other. The mechanisms of neurotransmitter abnormalities and intestinal dysfunction also play an important role. The connection between pathways is complex. NMDAR, PI3K/Akt, MAPK, Keap1/Nrf2/ARE, and NF-κB pathways can be connected into a pathway network by targets such as Ras, Akt, and IKK. The reasons for the improvement of natural substances are related to their specific structure, such as polyphenols with different hydroxyl groups. This review's purpose is to lay a foundation for exploring and developing more natural substances that can effectively improve the cognitive impairment caused by pesticides.

Postharvest ripening of two varieties of corns: Structure, antioxidant activities and physicochemical properties of zein.

The newly harvested Jidan 66 (JD66) and Liangyu 99 (LY99) varieties of corns were stored for 56 days at constant temperature of 15 and 25 °C with relative humidity of 55%. The postharvest ripening resulted in more disordered secondary structure and less compact tertiary conformation of zein. The emulsifying activity and foaming stability reached maximum after storage of corns at 15 and 25 °C for 14 days, while the emulsifying stability and foaming capacity were the highest at two temperatures of storage for 7 days and 28 days, respectively. Furthermore, zein had the highest viscoelasticity as well as the strongest antioxidant activities after the storage of JD66 at two temperatures for 28 days and the storage of LY99 at 15 °C for 42 days and at 25 °C for 28 days. Therefore, appropriate postharvest ripening of corns changed the structure of zein, improving its antioxidant activities and physicochemical properties.

Ultrasonic Treatment of Corn Starch to Improve the Freeze-Thaw Resistance of Frozen Model Dough and Its Application in Steamed Buns.

Modification of corn starch using ultrasonic waves to improve its freeze-thaw resistance in frozen model doughs and buns. Analysis was performed by rheometry, low-field-intensity nuclear magnetic resonance imaging, Fourier infrared spectroscopy, and scanning electron microscopy. The results showed that the addition of ultrasonically modified corn starch reduced the migration of water molecules inside the model dough, weakened the decrease of elastic modulus, and enhanced the creep recovery effect; the decrease in α-helical and ß-fold content in the model dough was reduced, the destruction of internal network structure was decreased, the exposed starch granules were reduced, and the internal interaction of the dough was enhanced; the texture of the buns became softer and the moisture content increased. In conclusion, ultrasound as a physical modification means can significantly improve the freeze-thaw properties of corn starch, providing new ideas for the development and quality improvement of corn-starch-based instant frozen pasta products.

Transglutaminase-induced soybean protein isolate cold-set gels treated with combination of ultrasound and high pressure: Physicochemical properties and structural characterization.

Soybean protein isolate (SPI) was treated by the combined exposure to ultrasound and high pressure and then subjected to transglutaminase (TGase)-catalyzed cross-linking to prepare SPI cold-set gels. The effects of combined treatments on physicochemical and structural properties of TGase-induced SPI cold-set gels were investigated. The combination of ultrasound and high pressure promoted the covalent disulfide bonds and ε-(γ-glutaminyl) lysine isopeptide bonds as well as non-covalent hydrophobic interactions, which further improved the gelation properties of SPI compared to ultrasound or high pressure alone. In particular, the 480 W ultrasound followed by high pressure treatment of gels led to higher strength (120.53 g), water holding capacity (95.39 %), immobilized water (93.92 %), lightness (42.18), whiteness (51.03), and elasticity (G' = 407 Pa), as well as more uniform and compact microstructure, thus resulting in the improved gel network structure. The combination of two treatments produced more flexible secondary structure, tighter tertiary conformation and higher denaturation degree of protein in the gels, leading to more stable gel structure. The structural modifications of SPI contributed to the improvement of its gelation properties. Therefore, the combined application of ultrasound and high pressure can be an effective method for improving the structure and properties of TGase-induced SPI cold-set gels.

Huangqin Decoction ameliorates ulcerative colitis by regulating fatty acid metabolism to mediate macrophage polarization via activating FFAR4-AMPK-PPARα pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Decoction (HQD), a traditional Chinese medicine (TCM) formula chronicled in Shang Han Lun, is safe and effective for treatment of ulcerative colitis (UC). AIM OF THE STUDY: To investigate the effect of HQD against dextran sulfate sodium (DSS)-induced UC mice by regulating gut microbiota and metabolites, and further explore the mechanism of fatty acid metabolism on macrophage polarization. MATERIALS AND METHODS: Based on 3% dextran sulfate sodium (DSS)-induced UC mice model, clinical symptoms observation (body weight, DAI, and colon length) and histological inspection were used to evaluate the efficacy of HQD and fecal microbiota transplantation (FMT) from HQD-treated mice. The gut microbiota and metabolites were detected by 16S rRNA sequencing and metabolomics analysis. The parameters of fatty acid metabolism, macrophage polarization, and FFAR1/FFAR4-AMPK-PPARα pathway were analyzed by immunofluorescence analysis, western blotting, and real-time PCR. Then, the effects of FFAR1 and FFAR4 on macrophage polarization were examined by agonists based on LPS-induced RAW264.7 cell model. RESULTS: The results showed that FMT, like HQD, ameliorated UC by improving weight loss, restoring colon length, and reducing DAI scores and histopathological scores. Besides, HQD and FMT both enhanced the richness of gut microbiota, and modulated intestinal bacteria and metabolites to achieve a new balance. Untargeted metabolomics analysis revealed that fatty acids, especially long-chain fatty acids (LCFAs), dominated in HQD against DSS-induced UC by regulating the gut microenvironment. Further, FMT and HQD recovered the expression of fatty acid metabolism-related enzymes, and simultaneously activated FFAR1/FFAR4-AMPK-PPARα pathway but suppressed NF-κB pathway. Combined with cell experiment, HQD and FMT promoted macrophage polarization from M1 toward M2, which were well associated with anti-inflammatory cytokines and combined with the activated FFAR4. CONCLUSIONS: The mechanism of HQD against UC was related to regulating fatty acid metabolism to mediate M2 macrophage polarization by activating the FFAR4-AMPK-PPARα pathway.