Mitochondrial-dependent oxidative phosphorylation is key for postnatal metabolic adaptation of alveolar macrophages in the lung.

Alveolar macrophages (AMs) seed in lung during embryogenesis and become mature in perinatal period. Establishment of acclimatization to environmental challenges is important, whereas the detailed mechanisms that drive metabolic adaptation of AMs remains to be elucidated. Here, we showed that energy metabolism of AMs was transformed from glycolysis prenatally to oxidative phosphorylation (OXPHOS) postnatally accompanied by up-regulated expression of mitochondrial transcription factor A (TFAM). TFAM deficiency disturbed mitochondrial stability and decreased OXPHOS, which finally impaired AM maintenance and function, but not AM embryonic development. Mechanistically, Tfam-deletion resulted in impaired mitochondrial respiration and decreased ATP production, which triggered endoplasmic reticulum (ER) stress to cause B cell lymphoma 2 ovarian killer (BOK) accumulation and abnormal distribution of intracellular Ca2+, eventually led to induce AM apoptotic death. Thus, our data illustrated mitochondrial-dependent OXPHOS played a key role in orchestrating AM postnatal metabolic adaptation.

Metabolic activation and cytochrome P450 inhibition of piperlonguminine mediated by CYP3A4.

Piperlonguminine (PLG) is a major alkaloid found in Piper longum fruits. It has been shown to possess a variety of biological activities, including anti-tumor, anti-hyperlipidemic, anti-renal fibrosis and anti-inflammatory properties. Previous studies have reported that PLG inhibits various CYP450 enzymes. The main objective of this study was to identify reactive metabolites of PLG in vitro and assess its ability to inhibit CYP450. In rat and human liver microsomal incubation systems exposed to PLG, two oxidized metabolites (M1 and M2) were detected. Additionally, in microsomes where N-acetylcysteine was used as a trapping agent, N-acetylcysteine conjugates (M3, M4, M5 and M6) of four isomeric O-quinone-derived reactive metabolites were found. The formation of metabolites was dependent on NADPH. Inhibition and recombinant CYP450 enzyme incubation experiments showed that CYP3A4 was the primary enzyme responsible for the metabolic activation of PLG. This study characterized the O-dealkylated metabolite (M1) through chemical synthesis. The IC50 shift assay showed time-dependent inhibition of CYP3A4, 2C9, 2E1, 2C8 and 2D6 by PLG. This research contributes to the understanding of PLG-induced enzyme inhibition and bioactivation.

Solid Electrolyte Interphase Recombination on Graphene Nanoribbons for Lithium Anode.

The practical application of lithium metal batteries is hindered by the lithium dendrite issue, which is seriously affected by the composition and structure of the solid electrolyte interphase (SEI). Modifying the SEI can regulate lithium dendrite formation and growth. Here, we experimentally realize a Li protective layer of LiTFSI-ether electrolyte induced a natural SEI grafted on graphene nanoribbons (SEI@GNRs) via their in situ reactions. The experimental results and theoretical calculations uncover that the 3D structure of SEI@GNRs can reduce the local current density and Li+ flux. The natural SEI in SEI@GNRs, especially the rich inorganic species of LiF, Li3N, and Li2S, decreases the Li+ nucleation overpotential, makes Li+ ion deposition and nucleation uniform, and isolates electron transport. Their synergetic effect suppresses Li dendrite formation and growth, increasing the electrochemical performance of lithium metal batteries. The design strategy is beneficial for the development of lithium metal batteries.

Band Structure Tuning via Pt Single Atom Induced Rapid Hydroxyl Radical Generation toward Efficient Photocatalytic Reforming of Lignocellulose into H2.

Photocatalytic lignocellulose reforming for H2 production presents a compelling solution to solve environmental and energy issues. However, achieving scalable conversion under benign conditions faces consistent challenges including insufficient active sites for H2 evolution reaction (HER) and inefficient lignocellulose oxidation directly by photogenerated holes. Herein, it is found that Pt single atom-loaded CdS nanosheet (PtSA -CdS) would be an active photocatalyst for lignocellulose-to-H2 conversion. Theoretical and experimental analyses confirm that the valence band of CdS shifts downward after depositing isolated Pt atoms, and the slope of valence band potential on pH for PtSA -CdS is more positive than Nernstian equation. These characteristics allow PtSA -CdS to generate large amounts of •OH radicals even at pH 14, while the capacity is lacking with CdS alone. The employment of •OH/OH- redox shuttle succeeds in relaying photoexcited holes from the surface of photocatalyst, and the •OH radicals can diffuse away to decompose lignocellulose efficiently. Simultaneously, surface Pt atoms, featured with a thermoneutral Δ G H ∗ $\Delta G_{\mathrm{H}}^{\mathrm{*}}$ , would collect electrons to expedite HER. Consequently, PtSA -CdS performs a H2 evolution rate of 10.14 µmol h-1 in 1 m KOH aqueous solution, showcasing a remarkable 37.1-fold enhancement compared to CdS. This work provides a feasible approach to transform waste biomass into valuable sources.

Network pharmacology and pharmacological evaluation of Wenzheng Jiedu Powder Modified Formula for neuropathic pain relief.

This study aimed to elucidate the mechanism of Wenzheng Jiedu Powder Modified Formula (WJPMF) in treating neuropathic pain (NP). Network pharmacology and experimental verification were integrated to explore the therapeutic effects and key targets of WJPMF. Active components, corresponding target genes, and absorption, distribution, metabolism, and excretion (ADME) genes of WJPMF against NP were screened from public databases. Network analysis and molecular docking were conducted to identify key targets and verify binding abilities. In vivo experiments were performed on spared nerve injury (SNI) rats to assess the analgesic effects and regulatory mechanisms of WJPMF. WJPMF significantly improved pain behaviors in SNI rats by regulating ATP-binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor alpha (PPARA), peroxisome proliferator-activated receptor gamma (PPARG), and superoxide dismutase 2 (SOD2) expression, which were key targets involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. WJPMF shows promising therapeutic potential for NP through the modulation of specific targets, offering a novel therapeutic strategy for managing NP.

K2CO3-Catalyzed (3 + 2) Cycloaddition Reaction of N-2,2,2-Trifluoroethylisatin Ketimines with Azodicarboxylates: Access to Spirooxindoles Containing Trifluoromethyl-1,2,4-triazolines.

Potassium carbonate-catalyzed (3 + 2) cycloaddition reaction between N-2,2,2-trifluoroethylisatin ketimines and azodicarboxylates has been developed, constructing a series of novel N-heterocycle infused spirooxindoles in good to excellent yields (up to 98%) under milder conditions. The presence of both biologically active oxindole and trifluoromethyl-1,2,4-triazoline moieties in these novel spirocyclic compounds would provide new lead structures in the discovery of heterocyclic compounds with potential pharmaceutical activities.

Overexpression of SCN5A overcomes ABC transporter-mediated multidrug resistance in acute myeloid leukemia through promoting apoptosis.

BACKGROUND: This study aimed to explore the effect and mechanism of SCN5A overcoming ATP-binding cassette (ABC) transporter-mediated multidrug resistance (MDR) in acute myeloid leukemia (AML) through promoting apoptosis. RESEARCH DESIGN AND METHODS: The tissues derived from AML patients were divided into Sensitive group and Resistance group according to the presence of drug-resistance. Human AML cell line HL-60 and drug-resistant strain HL-60/ADR were divided into HL-60/ADR-vector group, HL-60/ADR-SCN5A group, HL-60-vector group and HL-60-SCN5A group. RT-qPCR was used to detect the mRNA expression level of SCN5A; MTT assay to assess the survival rate and proliferation level of cells; flow cytometry to determine the apoptosis level; and western blot to check the levels of SCN5A, P-glycoprotein (P-gp), MDR protein 1 (MRP1), MDR gene 1 (MDR1), breast cancer resistance protein (BCRP), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) proteins in cells. RESULTS: SCN5A expressed lowly in drug-resistant AML tissues and cells. Up-regulation of SCN5A inhibited MDR in HL-60 cells, enhanced the chemosensitivity of HL-60/ADR, and increased the apoptosis levels of HL-60 and HL-60/ADR cells. However, over-expression of SCN5A inhibited the expression of MDR-related proteins. CONCLUSIONS: SCN5A may overcome ABC transporter-mediated MDR in AML through enhancing the apoptosis and inhibiting the expression of MDR proteins.

CALCRL induces resistance to daunorubicin in acute myeloid leukemia cells through upregulation of XRCC5/TYK2/JAK1 pathway.

Chemotherapy is the main treatment option for acute myeloid leukemia (AML), but acquired resistance of leukemic cells to chemotherapeutic agents often leads to difficulties in AML treatment and disease relapse. High calcitonin receptor-like (CALCRL) expression is closely associated with poorer prognosis in AML patients. Therefore, this study was performed by performing CALCRL overexpression constructs in AML cell lines HL-60 and Molm-13 with low CALCRL expression. The results showed that overexpression of CALCRL in HL-60 and Molm-13 could confer resistance properties to AML cells and reduce the DNA damage and cell cycle G0/G1 phase blocking effects caused by daunorubicin (DNR) and others. Overexpression of CALCRL also reduced DNR-induced apoptosis. Mechanistically, the Cancer Clinical Research Database analyzed a significant positive correlation between XRCC5 and CALCRL in AML patients. Therefore, the combination of RT-PCR and Western blot studies further confirmed that the expression levels of XRCC5 and PDK1 genes and proteins were significantly upregulated after overexpression of CALCRL. In contrast, the phosphorylation levels of AKT/PKCε protein, a downstream pathway of XRCC5/PDK1, were significantly upregulated. In the response study, transfection of overexpressed CALCRL cells with XRCC5 siRNA significantly upregulated the drug sensitivity of AML to DNR. The expression levels of PDK1 protein and AKT/PKCε phosphorylated protein in the downstream pathway were inhibited considerably, and the expression of apoptosis-related proteins Bax and cleaved caspase-3 were upregulated. Animal experiments showed that the inhibitory effect of DNR on the growth of HL-60 cells and the number of bone marrow invasions were significantly reversed after overexpression of CALCRL in nude mice. However, infection of XCRR5 shRNA lentivirus in HL-60 cells with CALCRL overexpression attenuated the effect of CALCRL overexpression and upregulated the expression of apoptosis-related proteins induced by DNR. This study provides a preliminary explanation for the relationship between high CALCRL expression and poor prognosis of chemotherapy in AML patients. It offers a more experimental basis for DNR combined with molecular targets for precise treatment in subsequent studies.

Zincophilic Metal-Organic-Framework Interface Mitigating Dendrite Growth for Highly Reversible Zinc Metal Batteries.

Aqueous Zn-ion batteries are the ideal candidate for large-scale energy storage systems owing to their high safety and low cost. However, the uncontrolled deposition and parasitic reaction of Zn metal anode hinder their commercial application. Here, the 2D metal-organic-framework (MOF) nanoflakes covered on the surface of Zn are proposed to enable dendrite-free for long lifespan Zn metal batteries. The MOF can facilitate the desolvation process to accelerate reaction kinetic due to its special channel structure. The abundant zincopilicity sites of MOF can realize the homogenous Zn2+ deposition. Consequently, their synergetic effect makes the MOF protected Zn anode good electrochemical performance with a long cycle life of 1400 h at 1 mA cm-2 and a high depth of discharge of 30 mAh cm-2 (DOD ≈ 54%) continued for over 700 h. This work provides a novel strategy for high-performance rechargeable Zn-ion batteries.

Effective Photocatalytic Ethanol Reforming into High-Value-Added Multicarbon Compound Coupled with H2 Production Over Pt-S3 Sites at PtSA -ZnIn2 S4 Interface.

Selective photocatalytic production of high-value acetaldehyde concurrently with H2 from bioethanol is an appealing approach to meet the urgent environment and energy issues. However, the difficult ethanol dehydrogenation and insufficient active sites for proton reduction within the catalysts, and the long spatial distance between these two sites always restrict their catalytic activity. Here, guided by the strong metal-substrate interaction effect, an atomic-level catalyst design strategy to construct Pt-S3 single atom on ZnIn2 S4 nanosheets (PtSA -ZIS) is demonstrated. As active center with optimized H adsorption energy to facilitate H2 evolution reaction, the unique Pt single atom also donates electrons to its neighboring S atoms with electron-enriched sites formed to activate the O─H bond in * CH3 CHOH and promote the desorption of * CH3 CHO. Thus, the synergy between Pt single atom and ZIS together will reduce the energy barrier for the ethanol oxidization to acetaldehyde, and also narrow the spatial distance for proton mass transfer. These features enable PtSA -ZIS photocatalyst to produce acetaldehyde with a selectivity of ≈100%, which will spontaneously transform into 1,1-diethoxyethane via acetalization to avoid volatilization. Meanwhile, a remarkable H2 evolution rate (184.4 µmol h-1 ) is achieved with a high apparent quantum efficiency of 10.50% at 400 nm.

Quasi-Solid-State All-V2 O5 Battery.

Solid-state symmetrical battery represents a promising paradigm for future battery technology. However, its development is hindered by the deficiency of high-performance bipolar electrodes and compatible solid electrolytes. Herein, a quasi-solid-state all-V2 O5 battery constructed by a binder-free carbon fabric-V2 O5 nanowires@graphene (CVOG) bipolar electrode and a softly cross-linked polyethylene oxide-based solid polymer electrolyte (SPE) is reported. The synergetic effect of nano-structuring of V2 O5 , hierarchical conductive network, and graphene wrapping endows the CVOG electrode with boosted reaction kinetics and suppressed vanadium dissolution. The cathodic and anodic reactions of CVOG are decoupled by electrochemical analysis, conceiving the feasibility of constructing all-V2 O5 full battery. In manifesting the solid-state all-V2 O5 battery, the robust and elastic SPE exhibits high ionic conductivity, tight/self-adaptable electrolyte-electrode contact, and a low charge-transfer barrier. The resultant solid-state full battery exhibits a high reversible capacity of 158 mAh g-1 at 0.1 C, good capacity retention of over 61% from 0.1 C to 2 C, and remarkable cycling stability of 77% capacity retention after 1000 cycles at 1 C, which surpass other solid-state symmetrical batteries. Hence, this work provides a practice of high-performance solid-state batteries with symmetrical configuration and is constructive for next-generation battery technology.

Role of HIF in fish inflammation.

The hypoxia-inducing factor (HIF) is a central transcription factor in cellular oxygen sensing and regulation. It is common that the inflammation always appears in many diseases, like infectious diseases in fishes, and the inflammation is often accompanied by hypoxia, as a hallmark of inflammation. Besides coordinating cellular responses to low oxygen, HIF-mediated hypoxia signaling pathway is also crucial for immune responses such as the regulations of innate immune cell phenotype and function, as well as metabolic reprogramming under the inflammation. However, the understanding of the molecular mechanisms by which HIFs regulate the inflammatory response in fish is still very limited. Here, we review the characteristics of HIF as well as its roles in innate immune cells and the infections caused by bacteria and viruses. The regulatory effects of HIF on the metabolic reprogramming of innate immune cells are also discussed and the future research directions are outlooked. This paper will serve as a reference for elucidating the molecular mechanism of HIF regulating inflammation and identifying treatment strategies to target HIF for fish disease.

Potentially suitable distribution areas of Populus euphratica and Tamarix chinensis by MaxEnt and random forest model in the lower reaches of the Heihe River, China.

Populus euphratica and Tamarix chinensis play a vital role in windbreak and sand fixation, maintaining species diversity and ensuring community stability. Managing and protecting the P. euphratica and T. chinensis forests in the Heihe River's lower reaches is an urgent issue to maintain the desert region's ecological balance. In this study, based on the distribution points of P. euphratica and T. chinensis species and environmental data, MaxEnt and random forest (RF) models were used to characterize the potential distribution areas of P. euphratica and T. chinensis in the lower reaches of the Heihe River. The results showed that the accuracy of the RF model was much higher than that of the MaxEnt model. Both the RF and MaxEnt models showed that the distance to the river greatly influenced the distribution of P. euphratica and T. chinensis. Furthermore, the RF model predicted significantly larger highly suitable areas for both P. euphratica and T. chinensis than the MaxEnt model. Our study enhances the understanding of the species' spatial distribution, offering valuable insights for practical management and conservation strategies.

Sanhuang Xiexin Decoction Ameliorates TNBC By Modulating JAK2-STAT3 and Lipid Metabolism.

OBJECTIVE: To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triple-negative breast cancer (TNBC) in mice and its underlying mechanism. METHODS: The high-performance liquid chromatography (HPLC) was used to quantitate and qualify SXD. A total of 15 female BALB/c mice were inoculated subcutaneously on the right hypogastrium with 3×105 of 4T1-Luc cells to establish TNBC mouse model. All mice were divided randomly into 3 groups, including phosphate buffered solution (PBS), SXD and doxorubicin (DOX) groups (positive drug). Additionally, tumor growth, pathological changes, serum lipid profiles, expression of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway and its key targets including inflammatory factors, cell cycle and epithelial-mesenchymal transition (EMT) markers were investigated. Besides, the biosafety of SXD was also evaluated in mice. RESULTS: Rhein, coptisine, berberine hydrochloride and baicalin were all found in SXD, and the concentrations of these 4 components were 0.57, 2.61, 2.93, and 46.04 mg/g, respectively. The mouse experiment showed that SXD could notably suppress the development of tumors and reduce the density of tumor cells (P<0.01). The serum lipid analysis and Oil-Red-O staining both showed the differences, SXD group exhibited higher serum adiponectin and HDL-C levels with lower TC and LDL-C levels compared to the PBS and DOX groups (P<0.05 or P<0.01), respectively. SXD also decreased the levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3) expressions and its downstream factors, including mostly inflammatory cytokine, EMT markers, S phase of tumor cells and vascular endothelial growth factor (VEGF) expression (P<0.05 or P<0.01), respectively. The biosafety assessment of SXD revealed low levels of toxicity in mice. CONCLUSION: SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism.

Discovery of novel tumor-targeted near-infrared probes with 6-substituted pyrrolo[2,3-d]pyrimidines as targeting ligands.

Since the overexpression of folate receptors (FRs) in certain types of cancers, a variety of FR-targeted fluorescent probes for tumor detection have been developed. However, the reported probes almost all have the same targeting ligand of folic acid with various fluorophores and/or linkers. In the present study, a series of novel tumor-targeted near-infrared (NIR) molecular fluorescent probes were designed and synthesized based on previously reported 6-substituted pyrrolo[2,3-d]pyrimidine antifolates. All newly synthesized probes showed specific FR binding in vitro, whereas GT-NIR-4 and GT-NIR-5 with a benzene and a thiophene ring, respectively, on the side chain of pyrrolo[2,3-d]pyrimidine exhibited better FR binding affinity than that of GT-NIR-6 with folic acid as targeting ligand. GT-NIR-4 also showed high tumor uptake in KB tumor-bearing mice with good pharmacokinetic properties and biological safety. This work demonstrates the first attempt to replace folic acid with antifolates as targeting ligands for tumor-targeted NIR probes.

Comparative efficacy of intraoperative radiotherapy and external boost irradiation in early-stage breast cancer: a systematic review and meta-analysis.

External boost radiotherapy (EBRT) and intraoperative radiotherapy (IORT) are shown to be effective in patients with early-stage breast cancer. However, the difference between IORT and EBRT for patients' prognosis remains to be elucidated. The purpose of this meta-analysis is to investigate differences in local recurrence (LR), distant metastases, disease free survival (DFS), and overall survival (OS) between these two therapies. We searched the Cochrane Library, PubMed, Web of Science and Embase, from inception to Jan 10th, 2022. We used The Cochrane risk-of-bias assessment tool to assess the risk of bias of the included studies, and the STATA15.0 tool was used for the meta-analyses. Eight studies were ultimately included. Meta-analysis demonstrated that there was an inconsistent finding in the long-term risk of LR between the two radiotherapies, and there was no significant difference in short-term risk of LR, the metastasis rate, DFS, and OS IORT would be more convenient, less time-consuming, less costly, and more effective at reducing side effects and toxicity. However, these benefits must be balanced against the potential for increased risk of LR in the long term.

High-Valence Mo Doping and Oxygen Vacancy Engineering to Promote Morphological Evolution and Oxygen Evolution Reaction Activity.

The rational design of high-efficiency, low-cost electrocatalysts for electrochemical water oxidation in alkaline media remains a huge challenge. Herein, combined strategies of metal doping and vacancy engineering are employed to develop unique Mo-doped cobalt oxide nanosheet arrays. The Mo dopants exist in the form of high-valence Mo6+, and the doping amount has a significant effect on the structure morphology, which transforms from 1D nanowires/nanobelts to 2D nanosheets and finally 3D nanoflowers. In addition, the introduction of vast oxygen vacancies helps to modulate the electronic states and increase the electronic conductivity. The optimal catalyst MoCoO-3 exhibits greatly increased active sites and enhanced reaction kinetics. It gives a dramatically lower overpotential at 50 mA cm-2 (288 mV), much smaller than that of the undoped counterpart (418 mV) and comparable to those of the recently reported electrocatalysts. Density functional theory results further verify that the increased electronic conductivity and optimized adsorption energy toward oxygen evolution reaction intermediates are mainly responsible for the enhanced catalytic activity. Moreover, the assembled two-electrode electrolyzer (MoCoO-3||Pt/C) exhibits superior performance with the cell potential decreased by 233 mV to reach a current density of 50 mA cm-2 with respect to the benchmark counterpart catalysts (RuO2||Pt/C). This work might contribute to the rational design of effective, low-cost electrocatalyst materials by combining multiple strategies.

The role of CcPTGS2a in immune response against Aeromonas hydrophila infection in common carp (Cyprinus carpio).

Prostaglandin-endoperoxide synthase 2 (PTGS2), a crucial enzyme in prostaglandin synthesis, catalyzes the conversion of arachidonic acid to prostaglandins and plays a significant role in the inflammatory response. This investigation aimed to determine the regulatory role of PTGS2a in the innate immune response to bacterial infection in fish. To achieve this objective, the CcPTGS2a gene was identified and characterized in common carp (Cyprinus carpio), and its function in immune defense was investigated. According to the sequence and structural analysis results, CcPTGS2a had an open reading frame of 1806 bp that encoded 602 amino acids. It was estimated that the protein's theoretical molecular weight was 69.0 kDa, and its isoelectric point was 8.10. The structure of CcPTGS2a was observed to be conserved, with an epidermal growth factor domain and a peroxidase domain present. Moreover, the amino acid sequence of CcPTGS2a exhibited significant homology with the amino acid sequences of several fish species. CcPTGS2a mRNA was detected in the healthy tissues of common carp, with higher expression in the head kidney, spleen, gills, and liver. Following the challenges with Aeromonas hydrophila and lipopolysaccharide, CcPTGS2a mRNA showed unique geographic and temporal expression patterns, with significant increases detected in the head kidney, gills, spleen, and liver. Additionally, the recombinant CcPTGS2a protein exhibited detectable bacterial binding to various bacteria. As determined by subcellular localization analysis, CcPTGS2a was predominantly localized in the nucleus and cytoplasm. Furthermore, it was discovered that the overexpression of CcPTGS2a stimulated the up-regulation of ferroptosis-related genes and inflammatory cytokine mRNA expression in fish and EPC (Epithelioma papulosum cyprinid) cells while concurrently reducing the bacterial load of A. hydrophila. In contrast, the interference of CcPTGS2a decreased the mRNA expression of ferroptosis-related genes and inflammatory cytokines in fish and EPC cells and increased the bacterial load of A. hydrophila. Notably, A. hydrophila stimulation resulted in the up-regulation of CcPTGS2a protein expression in EPC cells. These results suggested that CcPTGS2a was involved in the immune response to bacterial infections in common carp.

Integrated network pharmacology and gut microbiome analysis to reveal the mechanism of Qu-Zhuo-Tong-Bi decoction against hyperuricemia and gout.

ETHNOPHARMACOLOGICAL RELEVANCE: Qu-zhuo-tong-bi decoction (QZTBD) is a classic Chinese herbal medicine that has shown therapeutic efficacy in clinical practice against hyperuricemia and gout. However, the potential mechanisms of QZTBD remain poorly investigated. AIM OF THE STUDY: To assess the therapeutic effects of QZTBD on hyperuricemia and gout and to reveal its mechanisms of action. MATERIALS AND METHODS: A Uox-KO mouse model of hyperuricemia and gout was established, and QZTBD was administered at a dosage of 18.0 g/kg/d. Throughout the experimental period, the effects of QZTBD on gout symptoms were monitored and analyzed. The integrated network pharmacology and gut microbiota analysis strategy was conducted to explore the mechanism of QZTBD in the treatment of hyperuricemia and gout. Targeted metabolomic analysis was performed to investigate the variation of amino acids and Spearman's rank correlation analysis was conducted to reveal the relationship between the discrepant bacterial genera and the altered amino acid. Flow cytometry was utilized to analysis the proportion of Th17 and Treg cells, and the production of pro-inflammatory cytokines was measured by ELISA. qRT-PCR and Western blot assay were applied to detect the expression of mRNA and protein respectively. Autodock vina 1.1.2 was used to evaluate the docking interactions. RESULTS: QZTBD treatment showed remarkable efficacy against hyperuricemia and gout with respect to attenuation of disease activity metrics through gut microbiome recovery and intestinal immune homeostasis. The administration of QZTBD significantly elevated the abundance of Allobaculum and Candidatus sacchairmonas, corrected the aberrant amino acid patterns, repaired the impaired intestinal barrier, restored the balance of Th17/Treg cells via PI3K-AKT-mTOR pathway, and reduced the levels of inflammatory cytokines such as IL-1ß, IL-6, TNF-α and IL-17. Fecal microbiota transplantation from QZTBD treated mice demonstrated convincing evidence of efficacy and mechanism of QZTBD. CONCLUSION: Taken together, our study explores the therapeutic mechanism of an effective herbal formula, QZTBD, for gout treatment through remodeling gut microbiome and regulating the differentiation of CD4+ T cells via PI3K-AKT-mTOR pathway.