Development of novel imipridone derivatives with potent anti-cancer activities as human caseinolytic peptidase P (hClpP) activators.

Based on a clinically staged small molecular hClpP activator ONC201, a class of imipridone derivatives was designed and synthesized. These compounds were evaluated in a protease hydrolytic assay, as well as cell growth inhibition assays in three cancer cell lines, MIA PACA-2, HCT116, and MV4-11. A number of compounds that can more potently activate hClpP and more effectively inhibit cell growth in the three cancer cell lines than ONC201 were identified. The most potent compound, ZYZ-17, activated hClpP with an EC50 value of 0.24 µM and inhibited the growth of the three cancer cell lines with IC50 values of less than 10 nM. Mechanism studies for ZYZ-17 revealed that it potently activates cellular hClpP, efficiently induces the degradation of hClpP substrates, and robustly induces apoptosis in the three cancer cell lines. Furthermore, ZYZ-17 demonstrated a promising pharmacokinetic (PK) profile and exhibited highly potent in vivo antitumor activity in a pancreatic cancer MIA PACA-2 xenograft model in BALB/c nude mice.

Effectiveness of the small private online course-based flipped teaching program for enhancing nursing students' self-directed learning ability in the Surgical Nursing course: A practical study.

Small private online course-based flipped teaching is an innovative hybrid instructional approach that merges online and offline activities, fostering autonomous learning among students prior to class and facilitating the assimilation of knowledge within the confines of the classroom. To determine the effectiveness of the small private online course-based flipped teaching model on undergraduate nursing students' self-directed learning abilities, we performed a practice version of the small private online course-based flipped teaching program as a quasi-experiment, specifically designed for the Surgical Nursing course and assessed its effectiveness in students' self-directed learning abilities. To this end, a total of 264 students from the 2019 nursing major cohort were selected. Three classes comprising 131 students were randomly selected as the experimental group, and three other classes, comprising 133 students, were set as the control group. The results revealed no significant differences in the scores of self-directed learning abilities between the experimental and control groups before the experiment. After the experiment, the average scores on each dimension of the self-directed learning abilities improved significantly, and the final score of the experimental group was higher than that of the control group. The small private online course-based flipped teaching model can promote undergraduate nursing students' self-directed learning abilities, owing to its practicality and feasibility for the selected course.

Discovery of Dehydrogenated Imipridone Derivatives as Activators of Human Caseinolytic Protease P.

Based on the founding member of imipridones, ONC201, a class of dehydrogenated imipridone derivatives was designed, synthesized, and evaluated in a series of biochemical and biological assays as human caseinolytic protease P (hClpP) activators. Mechanism studies for one of the most potent compounds, XT6, indicated that it can potently bind to both recombinant and cellular hClpP, effectively promote the formation of hClpP tetradecamer, efficiently induce the degradation of hClpP substrates, robustly upregulate the expression of ATF4, and strongly inhibit the phosphorylations of AKT and ERK. More importantly, XT6 exhibited a promising pharmacokinetic profile in rats and could penetrate the blood brain barrier. It showed highly potent in vivo antitumor activity in a MIAPACA2 cell line derived pancreatic cancer model in BALB/c nude mice.

Access to diverse carbonyl compounds by catalyst-free and photoinduced aerobic cleavage of C=N bonds.

Functional group interconversion is of great significance in organic synthesis. However, aerobic cleavage of C=N bonds to access carbonyl compounds still suffered from some limitations such as harsh reaction conditions, stoichiometric oxidants, poor substrate scope and use of toxic reagents. Herein, we report a catalyst-free and photo-induced aerobic cleavage of C=N bonds to afford diverse carbonyl compounds using oxygen from air as green oxidant. This mild methodology permits N-tosylhydrazones converted into the corresponding carbonyl compounds including ketones, amides, aldehydes and carboxylic acids, showing broad functional group tolerance and compatibility. Moreover, the gram-scale reaction and post-modification of complicated molecules proved the applicability and efficiency of this strategy. Finally, a plausible mechanism was proposed based on spectroscopic investigations and detailed mechanistic studies.

Natural medicines-derived carbon dots as novel oral antioxidant administration strategy for ulcerative colitis therapy.

BACKGROUND: Ulcerative colitis (UC) is a chronic intestinal inflammation, resulting in a global healthcare challenge with no real specific medicine. Natural medicines are recognized as a potential clinical alternative therapy, but their applications are limited by poor solubility and low bioavailability. RESULTS: In this work, inspired by the natural medicines of ancient China, novel functional carbon dots derived from Magnetite and Medicated Leaven (MML-CDs) were synthesized by hydrothermal method, and confirmed their ultrasmall nano-size (3.2 ± 0.6 nm) and Fe doped surface structure, thereby with excellent gastrointestinal stability, remarkable capabilities in eliminating ROS, and highly biocompatibility. With no external stimuli, the oral administration of MML-CDs demonstrated obvious alleviation to UC. Further experiments pointed that MML-CDs could improve hemostasis capability, suppress inflammation reactions and oxidative stress, and up-regulate the expression of tight junction proteins. Furthermore, MML-CDs also showed well regulation in the dysbiosis of intestinal flora. CONCLUSION: Overall, above evidence reveals that green-synthesized MML-CDs can significantly alleviate intestinal bleeding, inhibit colon inflammation, and repair colonic barrier damage, further regulating intestinal flora and intestinal inflammation microenvironment. Our findings provide an efficient oral administration of MML-CDs as a novel therapy strategy for ulcerative colitis.

The efficient synthesis of three-membered rings via photo- and electrochemical strategies.

Three-membered rings, such as epoxides, aziridines, oxaziridines, cyclopropenes, vinyloxaziridines, and azirines, are recognized as crucial pharmacophores and building blocks in organic chemistry and drug discovery. Despite the significant advances in the synthesis of these rings through photo/electrochemical methods over the past decade, there has currently been no focused discussion and updated overviews on this topic. Therefore, we presented this review article on the efficient synthesis of three-membered rings using photo- and electrochemical strategies, covering the literature since 2015. In this study, a conceptual overview and detailed discussions were provided to illustrate the advancement of this field. Moreover, a brief discussion outlines the current challenges and opportunities in synthesizing the three-membered rings using these strategies.

The effect of matrine and glycyrrhizic acid on porcine reproductive and respiratory syndrome virus in Vitro and in vivo.

Porcine reproductive and respiratory syndrome (PRRS) is endemic worldwide, seriously affecting the development of the pig industry, but vaccines have limited protective effects against PRRSV transmission. The aim of this study was to identify potential anti-PRRSV drugs. We examined the cytotoxicity of seven compounds formulated based on the mass ratio of glycyrrhizic acid to matrine and calculated their inhibition rates against PRRSV in vitro. The results showed that the seven compounds all had direct killing and therapeutic effects on PRRSV, and the compounds inhibited PRRSV replication in a time- and dose-dependent manner. The compound with the strongest anti-PRRSV effect was selected for subsequent in vivo experiments. Pigs were divided into a control group and a medication group for the in vivo evaluation. The results showed that pigs treated with the 4:1 compound had 100% morbidity after PRRSV challenge, and the mortality rate reached 75% on the 8th day of the virus challenge. These results suggest that this compound has no practical anti-PRRSV effect in vivo and can actually accelerate the death of infected pigs. Next, we further analyzed the pigs that exhibited semiprotective effects following vaccination with the compound to determine whether the compound can synergize with the vaccine in vivo. The results indicated that pigs treated with the compound had higher mortality rates and more severe clinical reactions after PRRSV infection (p < 0.05). The levels of proinflammatory cytokines (IL-6, IL-8, IL-1ß, IFN-γ, and TNF-α) were significantly greater in the compound-treated pigs than in the positive control-treated pigs (p < 0.05), and there was no synergistic enhancement with the live attenuated PRRSV vaccine (p < 0.05). The compound enhanced the inflammatory response, prompted the body to produce excessive levels of inflammatory cytokines and caused body damage, preventing a therapeutic effect. In conclusion, the present study revealed that the in vitro effectiveness of these agents does not indicate that they are effective in vivo or useful for developing anti-PRRSV drugs. Our findings also showed that, to identify effective anti-PRRSV drugs, comprehensive drug screening is needed, for compounds with solid anti-inflammatory effects both in vitro and in vivo. Our study may aid in the development of new anti-PRRSV drugs.

Dynamic changes on sensory property, nutritional quality and metabolic profiles of green kernel black beans during Eurotium cristatum-based solid-state fermentation.

Eurotium cristatum, a unique probiotic in Fu brick tea, is widely used in food processing to enhance added values. Here, green kernel black beans (GKBBs) were solid-fermented with E. cristatum and dynamic changes in flavour, chemical composition and metabolites during fermentation were investigated. As results, E. cristatum fermentation altered aroma profiles and sensory attributes of GKBBs, especially reduced sourness. After fermentation, total polyphenolic and flavonoid contents in GKBBs were elevated, while polysaccharides, soluble proteins and short-chain fatty acids contents were decreased. E. cristatum fermentation also induced biotransformation of glycosidic isoflavones into sapogenic isoflavones. During fermentation, dynamic changes in levels of 17 amino acids were observed, in which 3 branched-chain amino acids were increased. Non-targeted metabolomics identified 51 differential compounds and 10 related metabolic pathways involved in E. cristatum fermentation of GKBBs. This study lays foundation for the development of green kernel black bean-based functional food products with E. cristatum fermentation.

Arterial Adventitial Vasa Vasorum Hyperplasia involved in Atherosclerotic Plaque Formation in a Rabbit Model.

OBJECTIVE: It was previously believed that atherosclerotic (AS) plaque starts to develop from the intima and that intraplaque vasa vasorum (VV) hyperplasia promotes adventitial VV (AVV) hyperplasia. However, recent studies have shown that arterial AVV hyperplasia precedes early intimal thickening, suggesting its possible role as an initiating factor of AS. To provide further insight into this process, in this study, we examine the evolution of AAV and VV development in a preclinical model of early AS with longitudinal ultrasound imaging. METHODS: Models of early AS were established. Duplex ultrasound scanning and contrast-enhanced ultrasound were performed for diagnosis. Pearson correlation tests were used to analyze the relationships between AVV hyperplasia and VV hyperplasia, or between AVV hyperplasia and intima-media thickness (IMT). RESULTS: During 0-12 wk of high-fat feeding, AVV gradually increased and intima-media thickened gradually in the observation area; in the 2nd wk of high-fat feeding, the observation area showed obvious AVV proliferation; at the 4th wk, the intima-media membrane became thicker; at the 12th wk, early plaque formation and intraplaque VV proliferation were observed. There was a strong positive correlation between AVV proliferation and IMT thickening and a strong negative correlation between AVV proliferation and the change rate of vessel diameter. CONCLUSION: This study demonstrated that AVV proliferation in the arteries occurred earlier than IMT thickening and was positively correlated with IMT. At present, the indicators of ultrasonic diagnosis of AS, such as IMT, Intraplaque VV, Echo property, all appear in the advanced stage of AS. The AVV may be an innovative diagnostic target for the early stage of AS plaque.

Tunable terahertz absorption of ion gel-graphene hybrids based on the Salisbury effect.

The gate-tunable absorption properties of graphene make it suitable for terahertz (THz) absorbers. However, the realization of a graphene-based THz absorber faces challenges between the difficulty of patterning graphene for processing and the intrinsically low absorbance of graphene with the high electric field needed to change the conductivity of graphene. This report presents an electrically tunable graphene THz absorber where a single-layer graphene film and a gold reflective layer are separated by a polyimide (PI) dielectric layer to form an easily fabricated three-layer Salisbury screen structure. The carrier density of the graphene layer can be efficiently tuned by a small external electrical gating (-5V-5 V) with the assistance of an ion gel layer. The voltage modulation of the Fermi energy level (EF) of graphene was confirmed by Raman spectra, and the variation of the device absorbance was confirmed using a THz time-domain spectroscopy system (THz-TDS). The measurements show that the EF is adjusted in the range of 0-0.5 eV, and THz absorbance is adjusted in the range of 60%-99%. The absorber performs well under different curvatures, and the peak absorbance is all over 95%. We conducted further analysis of the absorber absorbance by varying the thickness of the PI dielectric layer, aiming to examine the correlation between the resonant frequency of the absorber and the dielectric layer thickness. Our research findings indicate that the proposed absorber holds significant potential for application in diverse fields such as communication, medicine, and sensing.

Two-Step Perovskite Solar Cells with > 25% Efficiency: Unveiling the Hidden Bottom Surface of Perovskite Layer.

While significant efforts in surface engineering have been devoted to the conversion process of lead iodide (PbI2) into perovskite and top surface engineering of perovskite layer with remarkable progress, the exploration of residual PbI2 clusters and the hidden bottom surface on perovskite layer have been limited. In this work, a new strategy involving 1-butyl-3-methylimidazolium acetate (BMIMAc) ionic liquid (IL) additives is developed and it is found that both the cations and the anions in ILs can interact with the perovskite components, thereby regulating the crystallization process and diminishing the residue PbI2 clusters as well as filling vacancies. The introduction of BMIMAc ILs induces the formation of a uniform porous PbI2 film, facilitating better penetration of the second-step organic salt and fostering a more extensive interaction between PbI2 and the organic salt. Surprisingly, the oversized residual PbI2 clusters at the bottom surface of the perovskite layer completely diminish. In addition, advanced depth analysis techniques including depth-resolved grazing-incidence wide-angle X-ray scattering (GIWAXS) and bottom thinning technology are employed for a comprehensive understanding of the reduction in residual PbI2. Leveraging effective PbI2 management and regulation of the perovskite crystallization process, the champion devices achieve a power conversion efficiency (PCE) of 25.06% with long-term stability.

The transgenerational effects of maternal low-protein diet during lactation on offspring.

Environmental factors such as diet and lifestyle can influence the health of both mothers and offspring. However, its transgenerational transmission and underlying mechanisms remain largely unknown. Here, using a maternal lactation-period low-protein diet (LPD) mouse model, we show that maternal LPD during lactation causes decreased survival and stunted growth, significantly reduces ovulation and litter size, and alters the gut microbiome in the female LPD-F1 offspring. The transcriptome of LPD-F1 metaphase II (MII) oocytes shows that differentially expressed genes are enriched in female pregnancy and multiple metabolic processes. Moreover, maternal LPD causes early stunted growth and impairs metabolic health, which is transmitted over two generations. The methylome alteration of LPD-F1 oocytes can be partly transmitted to the F2 oocytes. Together, our results reveal that LPD during lactation transgenerationally affects offspring health, probably via oocyte epigenetic changes.

Hexylammonium Acetate-Regulated Buried Interface for Efficient and Stable Perovskite Solar Cells.

Due to current issues of energy-level mismatch and low transport efficiency in commonly used electron transport layers (ETLs), such as TiO2 and SnO2, finding a more effective method to passivate the ETL and perovskite interface has become an urgent matter. In this work, we integrated a new material, the ionic liquid (IL) hexylammonium acetate (HAAc), into the SnO2/perovskite interface to improve performance via the improvement of perovskite quality formed by the two-step method. The IL anions fill oxygen vacancy defects in SnO2, while the IL cations interact chemically with Pb2+ within the perovskite structure, reducing defects and optimizing the morphology of the perovskite film such that the energy levels of the ETL and perovskite become better matched. Consequently, the decrease in non-radiative recombination promotes enhanced electron transport efficiency. Utilizing HAAc, we successfully regulated the morphology and defect states of the perovskite layer, resulting in devices surpassing 24% efficiency. This research breakthrough not only introduces a novel material but also propels the utilization of ILs in enhancing the performance of perovskite photovoltaic systems using two-step synthesis.

Chrysin inhibits ferroptosis of cerebral ischemia/reperfusion injury via regulating HIF-1α/CP loop.

Chrysin is a natural flavonoid with powerful neuroprotective capacity. Cerebral ischemia/reperfusion injury (CIRI) is associated with oxidative stress and ferroptosis. Hypoxia-inducible factor 1α (HIF-1α) and ceruloplasmin (CP) are the critical targets for oxidation reactions and iron transport. But the regulatory mechanism between them is still unclear. Transient middle cerebral artery occlusion (tMCAO) model in rats and oxygen and glucose deprivation/re-oxygenation (OGD/R) model in PC12 cells were applied. Pathological tissue staining and biochemical kit were used to evaluate the effect of chrysin. The relationship between HIF-1α and CP was verified by transcriptomics, qRT-PCR and Western blot. In CIRI, HIF-1α/CP loop was discovered to be the regulatory pathway of ferroptosis. CIRI led to activation and nuclear translocation of HIF-1α, which promoted CP transcription and translation, and downstream ferroptosis. Inhibition of HIF-1α had opposite effect on CP and ferroptosis regulation. Overexpression of CP increased the expression of HIF-1α, nevertheless, inhibited the nuclear translocation of HIF-1α and alleviated CIRI. Silencing CP promoted HIF-1α elevation in nucleus and aggravated CIRI. Mechanistically, chrysin restrained HIF-1α nuclear translocation, thereby inhibiting CP transcription and translation, which in turn reduced downstream HIF-1α expression and mitigated ferroptosis in CIRI. Our results highlight chrysin restrains ferroptosis in CIRI through HIF-1α/CP loop.

Arterial Adventitial Vasa Vasorum Density Reflects The Progression Of Unstable Plaques: A Retrospective Clinical Study.

OBJECTIVE: Arterial adventitial vasa vasorum (AVV) plays an important role in the occurrence and development of atherosclerotic (AS) disease. AS is a systemic disease, and plaque is not only a local vascular event, but also occurs at multiple sites throughout the vascular bed. Currently, effective anti-AVV therapies are lacking. Therefore, we posed the following scientific questions: "does human carotid adventitial vasa vasorum density reflect plaque neovascularization and intimal-media hyperplasia in carotid?"; and "is it possible to reduce human AVV density by sonodynamic therapy (SDT)?" METHODS: A retrospective study was conducted on 160 patients with carotid atherosclerosis. Duplex ultrasound scanning (DUS), contrast-enhanced ultrasound (CEUS), coronary angiography, and coronary CT angiography (CTA) were used for diagnosis and screening. Pearson correlation tests and Receiver operating characteristic (ROC) curve were used to analyze the relationships between AVV hyperplasia, vasa vasorum (VV) hyperplasia and the intima-media thickness (IMT). SDT was developed for the treatment of arterial AVV hyperplasia and AS plaques. RESULTS: The presence of local AVV in carotid unstable plaques correlated with the echogenic properties of the carotid plaque and the extent of plaque progression; Furthermore local AVV hyperplasia in patients with carotid atherosclerotic plaques was associated with acute coronary syndrome (ACS) events; Local AVV hyperplasia in patients with carotid atherosclerotic plaques was associated with coronary artery stenosis. Notably, SDT reduced local AVV hyperplasia and shrank the plaques in human femoral and carotid atherosclerotic lesions. CONCLUSIONS: The presence of AVV in human carotid arteries reflects the severity of carotid and coronary artery AS. Further, SDT can reduce the hyperplasia of local AVV in human femoral and carotid plaques.

Ganshuang granule plays a pharmacological role in anti-alcoholic and anti-hangover via regulating alcohol metabolism and affecting neurotransmitters.

BACKGROUND: To explore the effect of Ganshuang granule on anti-alcoholic and anti-hangover and its potential mechanism. METHODS: SPF SD rats' drunken model and SPF Kunming mice's hangover model were used as models. RESULTS: Ganshuang granule could significantly reduce sleep time, the time to climb in mice, and significantly prolong the tolerance time and shorten sleep time in rats (p < 0.05). The blood ethanol concentration of rats in each administration group was lower than that in the model group at each time point (p < 0.05). Compared with the control group, the activities of ADH and ALDH in the liver of the model group were significantly decreased (p < 0.05); the content of DA and 5-HT in the striatum of the model group was significantly increased (p < 0.05); and the activity of AchE in the hippocampus was significantly decreased (p < 0.05). The above processes could be improved and regulated in the drug administration group. Compared with the control group, there was no significant difference between ADH and ALDH in the serum of the model group (p > 0.05). However, the activities of ADH and ALDH in the liver of drunk rats could be upregulated by Ganshuang granule (p < 0.05). CONCLUSION: Ganshuang granule has the pharmacological effects of anti-alcoholic and anti-hangover, which is related to regulating the activities of ADH and ALDH in the liver, the contents of DA and 5-HT in striatum, and the activity of AchE in the hippocampus.

Preparation and application of biocontrol formulation of nematode-trapping fungus-Duddingtonia flagrans.

The use of nematophagous fungi as a biological control strategy for parasitic gastrointestinal nematodes (GINs) in livestock holds promise as an innovative alternative approach. This study aimed to evaluate the clinical efficacy of a lyophilized Duddingtonia flagrans preparation, utilized in association with the anthelmintics ivermectin or albendazole, to control GINs in Tibetan sheep on a farm based in Qinghai Province. The experimental design included five groups: D. flagrans lyophilized preparation group; D. flagrans+ ivermectin combination tablets treatment group (0.6 tablets for each 10 kg b.w. containing 106 chlamydospores of D. flagrans); D. flagrans+ albendazole combination capsules treatment group (5 capsules for each 10 kg b.w. containing 106 chlamydospores of D. flagrans); ivermectin group (0.2 mg/kg); albendazole group (15 mg/kg), and a control group; The effect of these strategies was evaluated through the analysis of feces collected directly from the animals in each group at 24 h, 48 h, 72 h,96 h and 120 h after administration, by estimating the counts of fecal egg count reduction percentage (FECR) and larval development reduction percentage (LDR). The combination of D. flagrans lyophilized preparation with either ivermectin or albendazole yielded fecal egg and larval reduction rates of up to 100% within 72 h after oral administration, outperforming the groups treated with a single anthelmintic. Moreover, the application of the lyophilized preparation of D. flagrans chlamydospores in isolation demonstrated an 89.8% larval reduction rate. The formulation containing D. flagrans showed high predatory capacity after passage through the gastrointestinal tract of sheep and was effective for controlling gastrointestinal nematodes, which greatly reduced the pollution of the grassland, and avoid reinfection.

Discovery of Potent, Selective, and Orally Bioavailable DYRK2 Inhibitors for the Treatment of Prostate Cancer.

Prostate cancer (PCa) seriously threatens male health, and targeting dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) has been verified to reduce PCa burden, while the research progress on the DYRK2 inhibitors was relatively slow. In this work, we discovered DYRK2 inhibitor 12 (IC50 = 9681 nM) through virtual screening. Subsequently, we performed systematic structural optimization to obtain 54 (IC50 = 14 nM). Compound 54 exhibited high selectivity among 215 kinases and significantly suppressed the proliferation and metastasis of PCa cells in vitro. Moreover, compound 54 displayed high safety, favorable bioavailability, and potent tumor growth inhibitory activity in vivo, which could be used as a potential candidate in the discovery of novel anti-PCa drugs.

Pharmacokinetic differences in nicotine and nicotine salts mediate reinforcement-related behavior: an animal model study.

Since their introduction in the United States and Europe in 2007, electronic cigarettes (E-Cigs) have become increasingly popular among smokers. Nicotine, a key component in both tobacco and e-cigarettes, can exist in two forms: nicotine-freebase (FBN) and nicotine salts (NS). While nicotine salt is becoming more popular in e-cigarettes, the effect of nicotine salts on reinforcement-related behaviors remains poorly understood. This study aimed to compare the reinforcing effects of nicotine and nicotine salts in animal models of drug self-administration and explore potential mechanisms that may contribute to these differences. The results demonstrated that three nicotine salts (nicotine benzoate, nicotine lactate, and nicotine tartrate) resulted in greater reinforcement-related behaviors in rats compared to nicotine-freebase. Moreover, withdrawal-induced anxiety symptoms were lower in the three nicotine salt groups than in the nicotine-freebase group. The study suggested that differences in the pharmacokinetics of nicotine-freebase and nicotine salts in vivo may explain the observed behavioral differences. Overall, this study provides valuable insights into the reinforcing effects of nicotine as well as potential differences between nicotine-freebase and nicotine salts.

Effects of Fu brick tea polysaccharides on gut microbiota and fecal metabolites of HFD/STZ-induced type 2 diabetes rats.

The prevalence of type 2 diabetes mellitus (T2DM) has dramatically increased globally, and the antidiabetic effects and underlying mechanisms of the polysaccharides extracted from Fu brick tea (FBTP) were investigated in high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM rats. Administration of FBTP at 200 and 400 mg per kg bw significantly relieved dyslipidemia (i.e. TC, TG, LDL-C and HDL-C), insulin resistance (IR) and pancreas oxidative stress (i.e. CAT and GSH-Px) in T2DM rats. Mechanistically, FBTP rescued the HFD/STZ-induced alterations in the abundance of Bacteroidota, Actinobacteriota, Proteobacteria and Firmicutes. At the genus level, FBTP notably increased the abundance of Ruminococcus, Lactobacillus and Lachnospiraece_NK4A136_group, but reduced the population of Prevotella and Faecalibaculum in T2DM rats. FBTP also significantly elevated colonic short-chain fatty acid (SCFAs) levels. Moreover, apparent changes in amino acid absorption and metabolism were observed upon FBTP intervention. These findings suggested that FBTP might alleviate T2DM by reshaping the gut microbiota and regulating intestinal metabolites.