Recovery of iron and aluminum from iron-rich bauxite residue by an integrated phase reconstruction approach.

The comprehensive recovery of iron and aluminum from iron-rich bauxite residue (IRBR) is of critical importance both in terms of resource utilization and environment protection, which, however, is challenging due to the intertwined phases between Iron and aluminum. In this study, an integrated phase reconstruction approach, consisting of alkali roasting, two-stage column leaching, and carbonation decomposition, was proposed for Fe/Al recovery from IRBR. The results demonstrated that aluminum and sodium were fused into soluble substances such as sodium aluminate (Na7Al3O8, NaAlO2, and Na2O (Al2O3)11) in the alkali roasting process, allowing for the separation of Al and Fe in the subsequent leaching process. Following water/FeCl3 solution leaching, the removal efficiency of aluminum reached 84.66%, and Fe content in the residue could be enriched to 55.56%. Fe can be recycled as iron concentrate, and Al in the leaching solution with 75.95 g/L can be recovered in the form of Al(OH)3 through carbonation decomposition. This work provides an alternative strategy for the recovery of resources from IRBR, with potential implications for the sustainable development of the aluminum industry.

Transcriptional reprogramming restores UBE3A brain-wide and rescues behavioral phenotypes in an Angelman syndrome mouse model.

Angelman syndrome (AS) is a neurogenetic disorder caused by the loss of ubiquitin ligase E3A (UBE3A) gene expression in the brain. The UBE3A gene is paternally imprinted in brain neurons. Clinical features of AS are primarily due to the loss of maternally expressed UBE3A in the brain. A healthy copy of paternal UBE3A is present in the brain but is silenced by a long non-coding antisense transcript (UBE3A-ATS). Here, we demonstrate that an artificial transcription factor (ATF-S1K) can silence Ube3a-ATS in an adult mouse model of Angelman syndrome (AS) and restore endogenous physiological expression of paternal Ube3a. A single injection of adeno-associated virus (AAV) expressing ATF-S1K (AAV-S1K) into the tail vein enabled whole-brain transduction and restored UBE3A protein in neurons to ∼25% of wild-type protein. The ATF-S1K treatment was highly specific to the target site with no detectable inflammatory response 5 weeks after AAV-S1K administration. AAV-S1K treatment of AS mice showed behavioral rescue in exploratory locomotion, a task involving gross and fine motor abilities, similar to low ambulation and velocity in AS patients. The specificity and tolerability of a single injection of AAV-S1K therapy for AS demonstrate the use of ATFs as a promising translational approach for AS.

Generation, toxicity, and reduction of chlorinated byproducts: Overcome bottlenecks of electrochemical advanced oxidation technology to treat high chloride wastewater.

Electrochemical advanced oxidation process (EAOP) is recommended for high-strength refractory organics wastewater treatment, but the accompanying chlorinated byproduct generation becomes a bottleneck that limits the application of this technology to actual wastewater. In this study, we applied EAOP (0.4-40 mA cm-2) to treat ultrafiltration effluent of an actual landfill leachate, and quantitatively assessed the toxicities of the dominant chlorinated byproducts in EAOP-treated effluent. Considering both toxic effect and dose, it followed the order: active chlorine > chlorate > perchlorate > organochlorines. The toxic active chlorine could spontaneously decompose by settling. And secondary bioreactor originally serving for denitrification could be used to reduce perchlorate and chlorate. The effects of residual active chlorine and extra carbon addition on simultaneous denitrification, perchlorate, and chlorate reduction were investigated. It seemed that 20 mg of active chlorine was an acceptable level to bioactivity, and sufficient electron donors favored the removal of chlorate and perchlorate. Pseudomonas was identified as an active chlorine tolerant chlorate-reducing bacteria. And Thauera was responsible for perchlorate reduction under the conditions of sufficient carbon source supply. Our results confirmed that the perchlorate and chlorate concentrations in the effluent below their health advisory levels were achievable, solving the issue of toxic chlorinated byproduct generation during EAOP. This study provided a solution to realistic application of EAOP to treat high chloride wastewater.

De novo assembly and annotation of the CHOZN® GS-/- genome supports high-throughput genome-scale screening.

Chinese hamster ovary (CHO) cells have been used as the industry standard for the production of therapeutic monoclonal antibodies for several decades. Despite significant improvements in commercial-scale production processes and media, the CHO cell has remained largely unchanged. Due to the cost and complexity of whole-genome sequencing and gene-editing it has been difficult to obtain the tools necessary to improve the CHO cell line. With the advent of next-generation sequencing and the discovery of the CRISPR/Cas9 system it has become more cost effective to sequence and manipulate the CHO genome. Here, we provide a comprehensive de novo assembly and annotation of the CHO-K1 based CHOZN® GS-/- genome. Using this platform, we designed, built, and confirmed the functionality of a whole genome CRISPR guide RNA library that will allow the bioprocessing community to design a more robust CHO cell line leading to the production of life saving medications in a more cost-effective manner.

Lactobacillus rhamnosus Encapsulated in Alginate/Chitosan Microgels Manipulates the Gut Microbiome to Ameliorate Salt-Induced Hepatorenal Injury.

As the essential regulator of intestinal bacterial diversity, probiotics are a potential treatment for chronic high-salt diet (HSD)-induced metabolic dysfunction. Probiotic cells entrapped in microgels have been confirmed as being more effective than free cells in protecting bacteria against unfavorable conditions, that is, enhancing their stress resistance. This study explored the physiological mechanism by which probiotic microgels relieve HSD-induced hepatorenal injury. Herein, Lactobacillus rhamnosus was encapsulated in alginate-chitosan microgels which the percentage of alginate/chitosan was applied 1.5:0.5 (w/w) in this system, and the encapsulation significantly improved the probiotic viability in simulated gastrointestinal conditions. Mice were fed an HSD with L. rhamnosus (SDL) or L. rhamnosus microgels (SDEL). After 8 weeks of administration, dietary sodium was confirmed as inducing the hepatic and renal damages in mice, based on indicators, including serum biomarker levels, histopathological features of tissues, and pro-inflammatory cytokine contents in blood levels. However, the serum levels of urea nitrogen, creatinine, uric acid, glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, and alkaline phosphatase in the SDL and SDEL-fed mice were significantly lowered compared to the HSD-fed mice, especially in the SDEL group. HSD increased the abundances of Anaeroplasma, Enterorhabdus, Parvibacter, and Bacteroides, while the microgels increased the abundances of Lactobacillus, Bifidobacterium, Mucispirillum, and Faecalibaculum. Significant variations of fecal metabolome were validated for SDEL-treated mice, containing those linked to entero-hepatic circulation (e.g., cholic acid), carbohydrate metabolism (i.e., L-lactic acid), and increased antioxidants including citric acid. Furthermore, the probiotic microgels ameliorated intestinal damage by improving barrier and absorption functions. These results augmented existing knowledge on probiotic application for salt toxicity.

A Non-Isocyanate Route to Poly(Ether Urethane): Synthesis and Effect of Chemical Structures of Hard Segment.

A series of non-isocyanate poly(ether urethane) (PEU) were prepared by an environmentally friendly route based on dimethyl carbonate, diols and a polyether. The effect of the chemical structure of polyurethane hard segments on the properties of this kind of PEU was systematically investigated in this work. Polyurethane hard segments with different structures were first prepared from hexamethylene di-carbamate (BHC) and different diols (butanediol, hexanediol, octanediol and decanediol). Subsequently, a series of non-isocyanate PEU were obtained by polycondensation of the polyurethane hard segments with the polyether soft segments (PTMG2000). The PEU were characterized by GPC, FT-IR, 1H NMR, DSC, WAXD, SAXS, AFM and tensile testing. The results show that the urea groups generated by the side reaction affect the degree of crystallization of hard segments by influencing the hydrogen bonding of the hard segments molecular chains. The degree of hard segment crystallization, in turn, affects the thermal and mechanical properties of the polymer. The urea group content is related to the carbon chain length of the diol used for the synthesis of hard segments. When butanediol is applied to synthesize hard segment, the hard segment of the resulting PEU is unable to crystallize. Therefore, the tensile strength and modulus of elasticity of butanediol-based PEU is lowest among three, though it possesses the highest urea group content. When longer octanediol or decanediol is applied to synthesize the hard segment, the hard segments in the resulting polyether-based polyurethane are crystallizable and the resulting PEU possesses higher tensile strength.

Effects of operating conditions on disinfection by-product formation, calculated toxicity, and changes in organic matter structures during seawater chlorination.

This study systematically quantified the impacts of different operation conditions, e.g., pH, chlorine dosages, contact times, and temperatures towards the disinfection by-product (DBP) formation, integrated toxicity, and structural changes in seawater natural organic matter during seawater chlorination. Higher concentrations of total DBPs were found under longer contact times, higher chlorine dosages, higher temperatures, and lower pH. The concentration of tribromomethane, the most abundant DBP, was found lowest at pH 10. Monobromoacetic acid, dibromoacetonitrile, and dibromoacetaldehyde were the three main contributors to integrated cyto- and geno-toxicity, stressing the need to monitor DBPs based on their contributions to integrated toxicity, regardless they are regulated or nonregulated. The concentrations of total organic chlorine remained stable under different conditions, while those of total organic bromine increased with increasing contact times, chlorine dosages, and temperatures, but with decreasing pH, indicating the changes of toxicity in chlorinated seawater compared to drinking water or groundwater. Changes of ultraviolet absorbance at 254 nm and fluorescence excitation emission matrix values are useful indicators for monitoring the concentrations of high molecular weight adsorbable organic bromine and total organic halogen under all operating conditions.

Polymer solubility in ionic liquids: dominated by hydrogen bonding.

Polymer solubility in ionic liquids (ILs) cannot be predicted by the solubility parameter approach based on the "like dissolves like" principle. According to the Kamlet-Abraham-Taft (KAT) multi-parameter polarity scale, ILs can be categorized on the basis of hydrogen-bond acidity or basicity ones. The experimental observations, that acidic ILs easily dissolve basic polymers and basic ILs dissolve acidic polymers, reflect the complementary nature of hydrogen-bonding interactions. A quantitative hydrogen-bonding analysis is proposed for predicting the solubility by taking the product of ΔαΔß as an indicator of the competition between cross-association and self-association hydrogen bonding (H-bonding), where Δα is the difference of acidity parameters between the polymer and IL, and Δß is the difference of basicity. This solubility criterion has been validated by the solubility data of 19 polymers (11 acidic and 8 basic) in 11 ILs (7 acidic and 4 basic). These principles based on KAT parameters can be applied to other systems dominated by hydrogen bonding.

Mannose modified zwitterionic polyester-conjugated second near-infrared organic fluorophore for targeted photothermal therapy.

Cancer resistance has been the huge challenge to clinical treatment. A photothermal therapy of second near-infrared (NIR-II) organic dye small molecule has been used to conquer the cancer resistance. However, the available NIR-II dye lacks selectivity and spreads throughout the body. It has toxicity and indiscriminate burn injuries normal cells and tissues during therapy. Hence, to improve the therapeutic outcomes, herein, for the first time, we report the mannose-modified zwitterionic nanoparticles loading IR1048 dye, aiming to overcome cancer cellular resistance. The targeting molecule mannose has been applied to modify zwitterionic polyester, and the obtained polyester is employed to load IR1048 to prolong the circulation time in the blood and improve the stability of loaded dye, due to the good cytocompatibility of polyester and the antifouling properties of zwitterions. In vitro experimental results show that the pH-responsive targeted nanoparticles display satisfactory photophysical properties, prominent photothermal conversion efficiency (44.07%), excellent photothermal stability, negligible cytotoxicity for normal cells and strong photothermal toxicity to drug-resistant cancer cells. Moreover, due to the mannose targeting effect, cancer cells can endocytose the nanoparticles effectively. All these results demonstrate potential application of this alternative hyperthermal delivery system with remote-controllable photothermal therapy of tumor for accurate diagnosis by NIR-II fluorescence imaging.

Age-related compositional changes and correlations of gut microbiome, serum metabolome, and immune factor in rats.

Aging is a complex physiological process associated with degenerative disorder of metabolism and immune function, which contributes to the occurrence of senile diseases. The gut microbiota affects systemic inflammation in aging processes probably through metabolism, but their relationship is still unclear. In this study, 16S-rRNA-sequencing technology, gas chromatography-time-of-flight mass spectrometry (GC-TOFMS)-based metabolic profiling, and immune factor analysis combined with advanced differential and association analysis were employed to investigate the correlation between the microbiome, metabolome, and immune factors in male Wistar rats across lifespan. Our findings showed significant changes in the ileum microbiome and serum metabolome compositions across aging process. A two-level strategy was applied to demonstrate that key metabolites associated with age such as 4-hydroxyproline, proline, and lysine were clustered together and positively correlated with beneficial microbes including Bifidobacterium, Lactobacillus, and Akkermansia. Function analysis explored association between serum metabolite class and specific gut bacteria's metabolism pathways. Further correlation analysis on all the alteration patterns provided an interaction network of main immune factors such as IL-10, IgA, IgM, and IgG with key gut bacteria and serum metabolites. This study offers new insights into the relationship between immune factors, serum metabolome, and the gut microbiome.

Nondestructive Strategy to Effectively Enhance the Interfacial Adhesion of PBO/Epoxy Composites.

Low interfacial adhesion seriously limits the wide application of PBO fiber in composites. To solve this problem, a novel hierarchical reinforcement strategy was developed by introducing epoxy sizing, nanoreinforcement of amino-functionalized silicon dioxide (SiO2-NH2), and an interfacial compatibilizer of 2,6-bis(2-hydroxy-4-aminophenyl) benzobisoxazole (HABO) onto poly(p-phenylene benzobisoxazole) (PBO) fibers via a facile dip-coating approach. SiO2-NH2 and HABO were uniformly dispersed in epoxy sizing, forming an active interface layer. On this basis, wettability, surface roughness of the PBO fiber, and compatibility with the resin matrix were significantly improved, which gave 88.4 and 40.4% enhancement in the interfacial shear strength and interlaminar shear strength of the corresponding composites, respectively. Moreover, it should be noted that the outstanding mechanical and thermal properties of the PBO fiber were not impaired during the sizing treatment. In summary, our work provides an effective and damage-free approach to improve the interfacial adhesion of PBO/epoxy composites.

Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism.

Pu-erh tea displays cholesterol-lowering properties, but the underlying mechanism has not been elucidated. Theabrownin is one of the most active and abundant pigments in Pu-erh tea. Here, we show that theabrownin alters the gut microbiota in mice and humans, predominantly suppressing microbes associated with bile-salt hydrolase (BSH) activity. Theabrownin increases the levels of ileal conjugated bile acids (BAs) which, in turn, inhibit the intestinal FXR-FGF15 signaling pathway, resulting in increased hepatic production and fecal excretion of BAs, reduced hepatic cholesterol, and decreased lipogenesis. The inhibition of intestinal FXR-FGF15 signaling is accompanied by increased gene expression of enzymes in the alternative BA synthetic pathway, production of hepatic chenodeoxycholic acid, activation of hepatic FXR, and hepatic lipolysis. Our results shed light into the mechanisms behind the cholesterol- and lipid-lowering effects of Pu-erh tea, and suggest that decreased intestinal BSH microbes and/or decreased FXR-FGF15 signaling may be potential anti-hypercholesterolemia and anti-hyperlipidemia therapies.

Metabolome and gut microbiota variation with long-term intake of Panax ginseng extracts on rats.

Ginseng, a widely used functional food and food additive, has been proven to have promotion effects of health on the body. However, whether the long-term intake of Ginseng is beneficial or has side effects on an organism is still unclear. In this study, untargeted GC-TOFMS metabolomic analysis of serum, cecum and ileum intestinal contents was conducted to understand the effect of the long-term intake of Ginseng extracts. 16S rRNA microbial sequencing technology was applied to investigate the effect of Ginseng extracts on the structure of gut microbiota. Cytokines in spleen were detected to determine the effect of Ginseng extracts on the immune system. Compared to control groups, the metabolites in serum, cecum and ileum, such as amino acids, amines and other metabolites related to carbohydrate metabolism, significantly varied between the C and GS groups. Ginseng extracts affected the structure of gut microbiota with a decreased abundance of TM7, while the abundance of Proteobacteria, Methylobacteriaceae, Parasutterella, Sutterella increased in the GS group. The increased abundance of Bifidobacterium and Lactobacillus demonstrated that Ginseng extracts contribute to probiotic amplification. Highly correlated with Bifidobacterium and Lactobacillus, interleukin 4 (IL4), IL10 and immunoglobulin A (IgA) levels were significantly elevated after the long-term intake of Ginseng extracts. These results indicated that the long-term administration of Ginseng extracts positively affected the host-gut metabolism, immune system, the anti-inflammation process and the gut intestinal microbiota structure.

A modified method of high molecular weight adsorbable organic chlorine measurement in saline water: Dialysis pretreatment.

Adsorbable organic halogen is a mean to quantify total organic halogen, which is an important toxicity indicator in disinfection byproduct studies. However, quantification of low concentrations of adsorbable organic chlorine (AOCl) formation in seawater chlorination using the USEPA Method 9020B was found inaccurate due to the presence of high concentrations of chloride. In this study, a dialysis-based pretreatment technique was proposed, optimized and adopted to eliminate the interference of chloride in quantifying low concentrations of AOCl in seawater. A volumetric ratio of dialysis samples to continuous-flow deionized water at 1:1200 was found sufficient to remove over 99% of chloride. As a result, chloride to AOCl ratios can be reduced to less than 20,000, and the interference from chloride can thus be eliminated. The detainment of AOCl by the dialysis pretreatment depends on the molecular weight cutoff of the cellulose seamless dialysis membrane currently used, which was determined to be around 320 to 500 Da. The dialysis pretreatment can be used to measure AOCl concentrations in chlorinated seawater samples at pH 6.5 to 10.

Food withdrawal alters the gut microbiota and metabolome in mice.

Food withdrawal as a health-enhancing measure has beneficial effects on aging, disease prevention, and treatment. However, the cellular and molecular mechanisms involving gut microbial changes and metabolic consequences resulting from food withdrawal have yet to be elucidated. In this study, we subjected lean and obese mice to a dietary intervention that consisted of a 4-d complete food withdrawal and an 8-d 50% food withdrawal, and we studied changes in cecal microbiome and host serum metabolome. The abundance of potentially pathogenic Proteobacteria was decreased and Akkermansia muciniphila was elevated by food withdrawal in mice fed a high-fat diet (HFD). Meanwhile, food withdrawal decreased the abundance of metabolites in branched chain amino acid, lipid, and free fatty acid metabolisms in host serum, more so in HFD mice than in normal mice. Microbial predicted function also showed that food withdrawal decreased the abundance of microbes associated with predicted diseases in the HFD group but not in the normal chow group. Correlation between the microbiome data and metabolomics data revealed a strong association between gut microbial and host metabolic changes in response to food withdrawal. In summary, our results showed that food withdrawal was safer and more metabolically beneficial to HFD-induced obese mice than to normal lean mice, and the beneficial effects were primarily derived from the changes in gut microbiota, which were closely associated with the host metabolome.-Zheng, X., Zhou, K., Zhang, Y., Han, X., Zhao, A., Liu, J., Qu, C., Ge, K., Huang, F., Hernandez, B., Yu, H., Panee, J., Chen, T., Jia, W., Jia, W. Food withdrawal alters the gut microbiota and metabolome in mice.

Degradation Investigation of Selected Taste and Odor Compounds by a UV/Chlorine Advanced Oxidation Process.

Taste- and odor-causing (T&O) compounds are a major concern in drinking water treatment plants due to their negative impacts on the safety and palatability of water supply. This study explored the degradation kinetics and radical chemistry of four often-detected T&O compounds, geosmin (GSM), 2-methylisoborneol (MIB), benzothiazole (BT), and 2-isobutyl-3-methoxypyrazine (IBMP), in the ultraviolet/chlorine (UV/chlorine) advanced oxidation process. All experiments were carried out in a 700 mL photoreactor and the process effectively degraded the investigated T&O compounds in a slightly acidic environment. The degradation of T&O decreased with increasing pH but slightly with decreasing chlorine dosage. When the pH increased from 6 to 8, the pseudo-first-order rate constants of GSM, MIB, BT, and IBMP dropped from 2.84 × 10-3, 2.29 × 10-3, 3.64 × 10-3, and 2.76 × 10-3 s-1 to 3.77 × 10-4, 2.64 × 10-4, 6.48 × 10-4, and 6.40 × 10-4 s-1, respectively. Increasing the chlorine dosage slightly accelerated the degradation of the investigated T&O compounds, but excessive hypochlorous acid and hypochlorite scavenged the HO• radicals and reactive chlorine species (RCS). Generally, HO• primarily contributed to the degradation of all of the investigated T&O compounds as compared to RCS. The degradation by RCS was found to be structurally selective. RCS could not degrade GSM, but contributed to the degradation of MIB, BT, and IBMP. The results confirmed that the proposed oxidation process effectively degraded typical T&O compounds in aqueous phase.

Metabonomics Approach To Comparing the Antistress Effects of Four Panax ginseng Components in Rats.

Different components of Panax ginseng have different properties and medicinal effects. Metabonomics was a prospective approach to analyze the global response of endogenous metabolites to physiological and pathological processes. In this study, an untargeted metabonomics method using GC/TOFMS combined with multivariate statistical techniques was applied to compare entire metabolite differences and the antistress variations among four components of P. ginseng, namely, total ginsenosides (TG), panaxadiol (PD), panaxatriol (PT), and ginseng polysaccharide (PS), in Wistar rats. The results of metabolite analysis showed that numerous urine metabolites involving neurotransmitters, amino acids, organic acids, and gut microbiota metabolites were changed after administration of the four components of P. ginseng, with TG having the least impact on urinary metabolites. The urinary metabolite profiling of these rats exposed to acute combined stress (forced swimming and behavior restriction) demonstrated that the four ginseng components attenuated urine metabolite changes involving gut microbiota metabolites, tricarboxylic acid (TCA) cycle and energy metabolites, and organic acids to different degrees, with TG improving most of the metabolites altered by stress.

Strategy for an Association Study of the Intestinal Microbiome and Brain Metabolome Across the Lifespan of Rats.

There is increased appreciation for the diverse roles of the microbiome-gut-brain axis on mammalian growth and health throughout the lifespan. Numerous studies have demonstrated that the gut microbiome and their metabolites are extensively involved in the communication between brain and gut. Association study of brain metabolome and gut microbiome is an active field offering large amounts of information on the interaction of microbiome, brain and gut but data size and complicated hierarchical relationships were found to be major obstacles to the formation of significant, reproducible conclusions. This study addressed a two-level strategy of brain metabolome and gut microbiome association analysis of male Wistar rats in the process of growth, employing several analytical platforms and various bioinformatics methods. Trajectory analysis showed that the age-related brain metabolome and gut microbiome had similarity in overall alteration patterns. Four high taxonomical level correlated pairs of "metabolite type-bacterial phylum", including "lipids-Spirochaetes", "free fatty acids (FFAs)-Firmicutes", "bile acids (BAs)-Firmicutes", and "Neurotransmitters-Bacteroidetes", were screened out based on unit- and multivariant correlation analysis and function analysis. Four groups of specific "metabolite-bacterium" association pairs from within the above high level key pairs were further identified. The key correlation pairs were validated by an independent animal study. This two-level strategy is effective in identifying principal correlations in big data sets obtained from the systematic multiomics study, furthering our understanding on the lifelong connection between brain and gut.

Poly-pharmacokinetic Study of a Multicomponent Herbal Medicine in Healthy Chinese Volunteers.

The advent of mass spectrometry-based analytical technologies coupled with multivariate statistical methods offer tremendous new opportunities for understanding the pharmacokinetics (PKs) of multicomponent herbal medicines (HMs). We recently proposed a poly-PK strategy to characterize the concentration-time profile and the metabolic response profile of multicomponent HMs using an integrated phytochemical and metabolomics approach. Here, we provided the first example of the poly-PK strategy, in which we simultaneously characterized the PK as well as the metabolic response profiles of a Chinese HM, Huangqi decoction (HQD, consisting of Radix Astragali and Radix Glycyrrhizae), in healthy Chinese volunteers. Using the poly-PK approach, we identified 56 HQD-derived compounds and 292 biotransformed HQD metabolites in human plasma. Additionally, we acquired the concentration-time profiles of these plasma HQD metabolites and correlated them with a plasma metabolomics profile consisting of 166 human endogenous metabolites that were significantly altered in response to HQD intervention.

Sex-dependent effects on gut microbiota regulate hepatic carcinogenic outcomes.

Emerging evidence points to a strong association between sex and gut microbiota, bile acids (BAs), and gastrointestinal cancers. Here, we investigated the mechanistic link between microbiota and hepatocellular carcinogenesis using a streptozotocin-high fat diet (STZ-HFD) induced nonalcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) murine model and compared results for both sexes. STZ-HFD feeding induced a much higher incidence of HCC in male mice with substantially increased intrahepatic retention of hydrophobic BAs and decreased hepatic expression of tumor-suppressive microRNAs. Metagenomic analysis showed differences in gut microbiota involved in BA metabolism between normal male and female mice, and such differences were amplified when mice of both sexes were exposed to STZ-HFD. Treating STZ-HFD male mice with 2% cholestyramine led to significant improvement of hepatic BA retention, tumor-suppressive microRNA expressions, microbial gut communities, and prevention of HCC. Additionally the sex-dependent differences in BA profiles in the murine model can be correlated to the differential BA profiles between men and women during the development of HCC. These results uncover distinct male and female profiles for gut microbiota, BAs, and microRNAs that may contribute to sex-based disparity in liver carcinogenesis, and suggest new possibilities for preventing and controlling human obesity-related gastrointestinal cancers that often exhibit sex differences.