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Polycyclic aromatic hydrocarbons (PAHs) and dioxins are potential causes of multiple diseases by activating the aryl hydrocarbon receptor (AhR) pathway. Health risk assessment of chemicals primarily relies on the relative potency factor (RPF), although its accuracy may be limited when solely using EC50 values. The induction of cytochrome P4501A1 (CYP1A1) serves as a biomarker for AhR activation and is an integrator of dioxin-like toxicity. Here, we present a method for evaluating the risks associated with AhR activation using mathematical models of dose- CYP1A1 induction. The dose-effect curves for certain PAHs and dioxins, including Ant, BghiP, 1,2,3,4,7,8-HxCDD, and others, exhibited a non-classical S-shaped form. The toxic equivalent factor (TEF) profiles revealed a broad range of toxic equivalent factor values. The TEFs for PAHs ranged from approximately 0.01 to 6, with higher values being observed when the concentration was less than 10−10 M, with the exceptions of Ace, Phe, and BghiP. Most congeners of dioxins got the lowest TEF value at around 10−10 M, ranging from 0.04 to 1.00. The binding affinity of AhR to ligands did not display a strong correlation with the EC50 of CYP1A1 expression, suggesting that the AhR-mediated effects of PAHs and dioxins are not fixed but instead fluctuate with the dose. Air samples acquired from a parking area were used to compare the proficiency of RPF and our current approach. In the current method, naphthalene and chrysene were the primary contributors of PAHs to AhR-mediated risks in parking lots air samples, respectively. However, the contributions of naphthalene and chrysene could be disregarded in the RPF approach. • BaP and 2,3,7,8-TCDF were the strongest inducers of AhR activation in PAHs and dioxins, respectively. • Toxicity equivalency factor values varied from −0.5–6 and 0–2 for PAHs and dioxins. • Free energy and CYP1A1 expression had strong correlation in PAHs, but not in dioxins. • Nap is the main pollutant for AhR-mediated risk in actual air samples in our approach, whereas a BaP in the RPF approach. [ABSTRACT FROM AUTHOR]

Silica nanoparticles (SiNPs) could induce adverse pulmonary effects, but the mechanism was not clear enough. Metabolomics is a sensitive and high-throughput approach that could investigate the intrinsic causes of adverse health effects caused by SiNPs. The current investigation represented the first in vivo metabolomics study examining the chronic pulmonary toxicity of SiNPs at a low dosage, mimicking real human exposure situation. The recovery process after the cessation of exposure was also taken into consideration. Fisher 344 rats were treated with either saline or SiNPs for 6 months. Half of the animals in each group received an additional six-month period for recovery. The findings indicated that chronic low-level exposure to SiNPs resulted in notable alterations in pulmonary metabolism of amino acids, lipids, carbohydrates, and nucleotides. SiNPs exerted an impact on various metabolites and metabolic pathways which are linked to oxidative stress, inflammation and tumorigenesis. These included but were not limited to L-carnitine, spermidine, taurine, xanthine, and glutathione metabolism. The metabolic alterations caused by SiNPs exhibited a degree of reversibility. However, the interference of SiNPs on two metabolic pathways related to tumorigenesis was observed to persist after a recovery period. The two metabolic pathways are glycerophospholipid metabolism as well as phenylalanine, tyrosine and tryptophan biosynthesis. This study elucidated the metabolic alterations induced by chronic low-level exposure to SiNPs and presented novel evidence of the chronic pulmonary toxicity and carcinogenicity of SiNPs, from a metabolomic perspective. [Display omitted] • SiNPs affected amino acid, lipid, carbohydrate and purines & pyrimidines metabolism. • SiNPs-caused metabolic changes related to oxidative stress, inflammation and tumorigenesis. • The metabolome disturbance caused by SiNPs was reversible to some extent. • Tumorigenesis-related metabolic changes implied the potential of SiNPs-induced lung cancer. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) has an alarming mortality rate, and the fast-growing drug resistance of Mtb necessitates the discovery and application of new therapeutic agents. Although Sirt1 is a key regulator in metabolic, cardiovascular and other age-related diseases, its role in the regulation of antibacterial immunity is unclear. Here, we have reported that Sirt1 expression was decreased, and the decreased Sirt1 level was correlated with increased pro-flammatory cytokines and TAK1 phosphorylation in active TB patients. Our mechanistic experiments showed that Sirt1 direclty interacted with TAK1 and suppressed its activation. Further, Sirt1+/− macrophages infected with Mtb exhibited enhanced activation of TAK1, MAPKs and NF-κB, as well as simultaneously elevated expression of pro-inflammatory cytokines. Moreover, Sirt1+/− mice exhibited overt inflammation, as indicated by the significant abundance of pro-inflammatory cytokines, and were more susceptible to Mtb infection than wild-type mice. Overall, the findings indicate that inhibition of Sirt1 expression by Mtb infection enhances TAK1 activation, and this in turn enhances the secretion of IL-6 and TNF-α via activation of the p65/p38/JNK/ERK signaling pathways. Treatment with resveratrol, which is known that one of its multiple effects is Sirt1 activation, in Mtb -infected macrophages inhibited the activation of TAK1, MAPK and NF-κB pathways, and the pro-inflammatory cytokine levels. Consitently, mice treated with resveratrol were more resistant to Mtb infection. The potent therapeutic effects of resveratrol against Mtb infection indicate that Sirt1 could be a novel therapeutic target for the treatment of TB. • Sirt1 expression was low in PBMCs from clinical TB samples and Mtb -infected murine peritoneal macrophages. • Sirt1 interacted with TAK1 and inhibited its phosphorylation and ubiquitination. • Sirt1+/− mice were more susceptible to Mtb infection than WT mice. • Resveratrol alleviated Mtb infection through anti-inflammatory mechanisms. [ABSTRACT FROM AUTHOR]

Abstract Modified nano-graphene quantum dots (M-GQDs) are widely used in bioimaging, drug delivery, and chemical engineering. Because M-GQDs could induce reactive oxygen species and DNA damage, we hypothesized that M-GQDs modulate DNA methylation. To test this hypothesis, zebrafish were exposed to reduced, hydroxylated, or aminated GQDs (graphene quantum dots) at different concentrations for 7 days; global DNA methylation in liver, gill, and intestine was then studied. M-GQDs induced global DNA hypermethylation in various tissues in a dose-dependent manner. The global DNA methylation of reduced and aminated GQDs exposure showed a significant increase in intestines even at low concentrations (2 mg/L), suggesting that intestines are the main target for these two M-GQDs. The effects of global DNA methylation were evaluated 14 days after exposure had ceased. DNA methylation in the livers of exposure groups was significantly higher than in control zebrafish. Global DNA methylation increased in livers of zebrafish even after exposure to aminated GQDs (2 mg/L) had ceased, indicating a more complex mechanism of DNA methylation deregulation. The present results showed that chemical groups in the surface of GQDs are a critical factor for modulating DNA methylation. Graphical abstract fx1 Highlights • OH-GQDs, rGQDs, and NH 2 -GQDs lead to global DNA hypermethylation. • M-GQDs induced DNA hypermethylation in a dose-dependent manner. • Tissue specificity DNA hypermethylation induced by M-GQDs were observed. • Abnormal DNA methylation in the liver and intestine persists after exposure ceases. • Surface chemical groups of M-GQDs are critical for modulating DNA methylation. [ABSTRACT FROM AUTHOR]

Abstract Hepatocellular carcinoma (HCC) is a lethal malignancy with few effective options for therapeutic treatment in its advanced stages. Metformin, a first-line oral agent used in the treatment of type 2 diabetes, exhibits efficacy in metabolic reprogramming fueling changes in cell growth and proliferation for multiple cancer types, including HCC. However, the molecular mechanism by which metformin delays hepatocarcinogenesis in individuals with hepatic steatosis remains rare. Here, we investigate the preventive efficacy of metformin in a rapid AKT/c-Met-triggered HCC mouse model featuring excessive levels of steatosis. Hematoxylin and eosin staining, Oil Red O staining and immunoblotting were applied for mechanistic investigations. Pharmacological and biochemical strategies were employed to illuminate molecular evidence for HCC cell lines. The results show that metformin obstructs the malignant transformation of hepatocytes in AKT/c-Met mice. Mechanistically, metformin reduces the expression of phospho-ERK (Thr202/Tyr204) and two forms of proto-oncogenes, Cyclin D1 and c-Myc, in AKT/c-Met mice. Moreover, metformin ameliorates FASN-mediated aberrant lipogenesis and HK2/PKM2-driven ATP generation in vivo. Furthermore, metformin represses the expression of FASN and HK-2 by targeting c-Myc in an AMPK-dependent manner in vitro. In addition, metformin is effective at inhibiting PKM2 expression in the presence of an AMPK inhibitor compound C, suggesting that its functioning in PKM2 is AMPK-independent. Our study experimentally validates a novel molecular mechanism by which metformin alleviates enhanced lipogenesis and high energy metabolism during hepatocarcinogenesis, indicating that metformin may serve as an agent for the prevention of HCC in patients with nonalcoholic fatty liver diseases. Highlights • Metformin delays AKT/c-Met-driven hepatocarcinogenesis in mice. • Metformin attenuates lipogenesis and ATP generation in AKT/c-Met HCC mice. • Metformin suppresses the expression of FASN and HK-2 in an AMPK/c-Myc dependent manner. • Metformin AMPK-independently reduces the expression of PKM2. [ABSTRACT FROM AUTHOR]

Abstract Samples of soil, earthworms, and tree roots from the forest ecosystem in the Dexing Pb/Zn mining area of Jiangxi Province were collected and the status of trace metal pollution analyzed to assess potential ecological risks. Chemometric and geographic information system methods were used to identify and describe the spatial distributions and the main contamination sources of trace metals. The order of potential ecological risks of trace metals in this area are as follows: cadmium (Cd) > arsenic (As) > copper (Cu) > nickel (Ni) > lead (Pb) > chromium (Cr) > zinc (Zn). Elemental spatial distribution maps showed the existence of zones heavily polluted by trace metals around the mining area. Earthworms and roots of three tree species were also heavily contaminated, with concentrations of trace metals in earthworms much higher than in previous studies. The potential ecological risk index and other soil quality indices indicated that soil had moderate to severe contamination and there were high ecological risks, with Cd making the greatest contribution. Multivariate statistical analyses showed that Cd, As, Cu, Pb, and Zn in soil came from a mining activity source, whereas Ni and Cr primarily originated from a natural source. Graphical abstract fx1 Highlights • Quality indicators, multivariate analysis and GIS mapping used to assess the pollution and ecological risk of trace elements. • Forest soils were polluted by trace metals with moderate risk. • Trace metals in the soil of the mining area are potentially harmful to organism. [ABSTRACT FROM AUTHOR]

The paper presents a novel solution to the 2022 National NLP Clinical Challenges (n2c2) Track 3, which aims to predict the relations between assessment and plan subsections in progress notes. Our approach goes beyond standard transformer models and incorporates external information such as medical ontology and order information to comprehend the semantics of progress notes. We fine-tuned transformers to understand the textual data and incorporated medical ontology concepts and their relationships to enhance the model's accuracy. We also captured order information that regular transformers cannot by taking into account the position of the assessment and plan subsections in progress notes. Our submission earned third place in the challenge phase with a macro-F1 score of 0.811. After refining our pipeline further, we achieved a macro-F1 of 0.826, outperforming the top-performing system during the challenge phase. Our approach, which combines fine-tuned transformers, medical ontology, and order information, outperformed other systems in predicting the relationships between assessment and plan subsections in progress notes. This highlights the importance of incorporating external information beyond textual data in natural language processing (NLP) tasks related to medical documentation. Our work could potentially improve the efficiency and accuracy of progress note analysis. [Display omitted] • An NLP pipeline that achieved a top-3 performance in 2022 n2c2 Track 3. • Fine-tuned transformer-based models to understand the semantics of progress notes. • Integrated medical ontology and order information to imporve the transformer models. • Designed an ensemble strategy to further boost our system performance. [ABSTRACT FROM AUTHOR]

Epidemiological evidence increasingly suggests that air pollutants are intimately associated with the incidence and mortality of cardiovascular diseases (CVDs). However, studies on the association between chronic exposure to air pollutants and changes in left cardiac function and structure are limited. In our cross-sectional study, 3145 participants were enrolled from 6 provinces to explore the relationship between long-term air pollutants, cardiac structure, and cardiovascular function (e.g., blood lipids, blood pressure and pulse) in Chinese adults. Our study showed that exposure to five pollutants (NO 2 , O 3 , PM 1 , PM 2.5 and PM 10) was associated with reduced left ventricular systolic function based on EF and SV parameters. These pollutants were also associated with increased pulses, where smaller particle sizes correlated significantly with pulses. Second, except for O 3 , four pollutants were associated with decreased left ventricular diastolic parameters LVIDd and EDV and increased cardiac structural parameter IVSd. In addition, exposures to NO 2 , O 3 and PM 10 were positively correlated with triglycerides in blood lipids. Overall, this study showed that chronic pollutant exposure is strongly associated with impaired left ventricular function in Chinese adults. [Display omitted] • NO 2 , O 3 and PM were associated with decline in left ventricular systolic function. • PM were associated with decrease in left ventricular diastolic function. • NO 2 and PM were associated with increased interventricular septal thickness. • NO 2 , O 3 and PM 10 was associated with increasing of TG levels. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) membrane forms an elaborate network of tubules and sheets that is continuously remodeled. This dynamic behavior requires membrane fusion that is mediated by dynamin-like GTPases: the atlastins in metazoans and Sey1p and related proteins in yeast and plants. Crystal structures of the cytosolic domains of these membrane proteins and biochemical experiments can now be integrated into a model that explains many aspects of the molecular mechanism by which these membrane-bound GTPases mediate membrane fusion. [ABSTRACT FROM AUTHOR]

Whey protein isolate (WPI) interacts with cinnamaldehyde (CA) to form conjugates with superior functional properties, which are affected by the conjugate structures formed by different food processing techniques, especially heating treatment. Initially, we compared three preparation methods of conjugates, including heating WPI before interacting with CA [(HWPI)/CA)], heating the resulting conjugates without heating WPI initially [H-(WPI/CA)], and the normal conjugates without any heating process (WPI/CA). Subsequently, these conjugates were used to stabilize emulsions for the encapsulation and delivery of β-carotene. Both the aforementioned heating methods increased the interaction and enhanced the conjugates' surface hydrophobicity. Synchronous fluorescence suggested that heating expanded the protein structure and exposed hydrophobic groups, while higher CA concentration had a shielding effect on this process. Moreover, H-(WPI/CA) conjugates reduced the interfacial tension to 4.38 mN/m, resulting in the best emulsification, which effectively stabilized emulsions and protected β-carotene from the influence of temperature. H-(WPI/CA) conjugates helped to maintain the retention rate at more than 70% within 28 days and improved β-carotene bioaccessibility during digestion. This knowledge provides insights into investigating the relationship between conjugates preparation methods and their properties, and is of great significance for developing a novel multifunctional food ingredient system based on protein modification. • Heating treatment could enhance the interaction between WPI and CA. • WPI/CA conjugate after heating treatment had better stability effect on emulsion. • H-(WPI/CA) conjugate had the best protective effect on β-carotene. • H-(WPI/CA) conjugate emulsion had the highest bioaccessibility of β-carotene. [ABSTRACT FROM AUTHOR]

Abstract: SH2-B, APS, and Lnk constitute a family of adapter proteins that modulate signaling by protein tyrosine kinases. These adapters contain an N-terminal dimerization region, a pleckstrin homology domain, and a C-terminal Src homology-2 (SH2) domain. SH2-B is recruited via its SH2 domain to various protein tyrosine kinases, including Janus kinase-2 (Jak2) and the insulin receptor. Here, we present the crystal structure at 2.35 Å resolution of the SH2 domain of SH2-B in complex with a phosphopeptide representing the SH2-B recruitment site in Jak2 (pTyr813). The structure reveals a canonical SH2 domain-phosphopeptide binding mode, but with specific recognition of a glutamate at the +1 position relative to phosphotyrosine, in addition to recognition of a hydrophobic residue at the +3 position. Biochemical studies of SH2-B and APS demonstrate that, although the SH2 domains of these two adapter proteins share 79% sequence identity, the SH2-B SH2 domain binds preferentially to Jak2, whereas the APS SH2 domain has higher affinity for the insulin receptor. This differential specificity is attributable to the difference in the oligomeric states of the two SH2 domains: monomeric for SH2-B and dimeric for APS. [Copyright &y& Elsevier]

• Early-life noise exposure causes neurocognitive and pathological changes in rats. • Noise exposure alters gut microbiota, metabolic profile and endothelial barrier. • Gut microbiota and SCFAs play key roles in neural effects of noise in early life. • Early-life noise exposure causes gut-brain response in a sex-dependent manner. Epidemiological investigations show that noise exposure in early life is associated with health and cognitive impairment. The gut microbiome established in early life plays a crucial role in modulating developmental processes that subsequently affect brain function and behavior. Here, we examined the impact of early-life exposure to noise on cognitive function in adolescent rats by analyzing the gut microbiome and metabolome to elucidate the underlying mechanisms. Chronic noise exposure during early life led to cognitive deficits, hippocampal injury, and neuroinflammation. Early-life noise exposure showed significant difference on the composition and function of the gut microbiome throughout adolescence, subsequently causing axis-series changes in fecal short-chain fatty acid (SCFA) metabolism and serum metabolome profiles, as well as dysregulation of endothelial tight junction proteins, in both intestine and brain. We also observed sex-dependent effects of microbiota depletion on SCFA-related beneficial bacteria in adolescence. Experiments on microbiota transplantation and SCFA supplementation further confirmed the role of intestinal bacteria and related SCFAs in early-life noise-exposure-induced impairments in cognition, epithelial integrity, and neuroinflammation. Overall, these results highlight the homeostatic imbalance of microbiota–gut–brain axis as an important physiological response toward environmental noise during early life and reveals subtle differences in molecular signaling processes between male and female rats. [ABSTRACT FROM AUTHOR]

Seneca Valley virus (SVV) is a member of the Picornaviridae family, which has been used to treat neuroendocrine cancer. The innate immune system plays an important role in SVV infection. However, few studies have elucidated the relationship between SVV infection and the host's antiviral response. In this study, SVV replication could induce the degradation of RIG-I in HEK-293T, SW620 and SK6 cells. And overexpressing retinoic acid-inducible gene I (RIG-I) could significantly inhibit SVV propagation. The viral protein 2C and 3C were essential for the degradation of RIG-I. Furthermore, 2C and 3C significantly reduced Sev or RIG-I-induced IFN-β production. Mechanistically, 2C and 3C induced RIG-I degradation through the caspase signaling pathway. Taken together, we demonstrate the antiviral role of RIG-I against SVV and the mechanism by which SVV 2C and 3C weaken the host innate immune system. [ABSTRACT FROM AUTHOR]

Breast cancer has become the number one cancer in the world, and intestinal flora may be closely linked to it. Geographic location also has an important impact on human intestinal flora. We conducted the first study on the intestinal flora of breast cancer patients and non-breast cancer patients in a tropical region - Hainan Province in China. At the same time, Pacbio platform based on third-generation sequencing was used for the first time to conduct 16S full-length sequencing of fecal microorganism DNA. We completed the species diversity analysis and differential species analysis of the intestinal flora between the two groups, inferred their functional genetic composition and performed functional difference analysis. There were statistically significant differences in alpha diversity between the two groups in Hainan Province. By species composition difference analysis, at the phylum level, Bacteroidales (P = 0.006) and Firmicutes (P = 0.002) was differed between the two groups, and at the genus level, 17 breast cancer-related differential species such as Bacteroides were screened. According to the five grouping methods including ER level, PR level, HER2 status, Ki67 index and histological grade of breast cancer patients, 4, 1, 9, 6, 5 differential microbiota were screened out respectively, which were in total 25 (P < 0.05 for all subgroups). The functional prediction and difference analysis revealed two functional metabolisms with significant differences between the two groups of microbes (P < 0.05). These results suggest that breast cancer is associated with changes in the composition and function of intestinal flora. These microflora and functional differences may become biomarkers or new targets for diagnosis and treatment of breast cancer. • First study on the intestinal flora of breast cancer patients in Hainan Province. • First use PacBio to conduct 16 S full length sequencing of fecal microorganism DNA. • The different strains found may become new biomarkers or targets of breast cancer. [ABSTRACT FROM AUTHOR]

• Melatonin inhibited the apoptosis of sheep endometrial epithelial cells At least in part through its receptors. • The regulation of melatonin on apoptosis of sheep endometrial epithelial cells is partly achieved by regulating estrogen function. • PGR antagonist (RU486) is not abolished the inhibition of melatonin on apoptosis of sheep endometrial epithelial cells. Melatonin potentially regulates the female animal reproductive function, but its regulatory mechanism in the apoptosis of sheep endometrial epithelial cells (SEECs) remains to be elucidated. In the present study, immunofluorescence staining, western blotting, and quantitative real-time polymerase chain reaction were performed to detect the distribution of melatonin receptors (MT1 and MT2) in the uterus of sheep and the effect of melatonin via the receptor and non-receptor pathways on the apoptosis of SEECs in vitro. The results showed that melatonin inhibits the apoptosis of SEECs to varying degrees to regulate the expression of estrogen receptors (ERs) and progesterone receptors (PGR) via its interaction with MT1 and MT2. In addition, the ER antagonist partially relieved the inhibitory effect of melatonin on the apoptosis of SEECs, while the PGR antagonist did not. Thus, melatonin mediates endometrial epithelial apoptosis through the MT receptors and also by regulating estrogen function. This study provides evidence of the regulatory mechanism of melatonin on the physiological function of the sheep uterus. [ABSTRACT FROM AUTHOR]

Sirtuin 6 (SIRT6) has recently been demonstrated to play an important role in the regulation of longevity in mammals. We therefore aimed to determine whether common variations in the SIRT6 gene are associated with human longevity. Five tag single nucleotide polymorphisms (SNPs) across the SIRT6 gene and its 5 kb up-/downstream region, including rs350852, rs350844, rs352493, rs4807546 and rs3760905, have been successfully determined in 616 unrelated Chinese long-lived individuals (LLIs) (mean age: 102.4 ± 2.3 years) and 846 younger controls (mean age: 48.9 ± 10.6 years) from Hainan Island, China. The allele and genotype frequencies of the five SNPs showed no statistically significant difference between the LLIs and controls (all P > 0.05). The five SNPs were in strong linkage disequilibrium and defined seven common haplotypes. Likewise, no association between these haplotypes and longevity was observed (all P > 0.05). The present study reveals that common genetic variations in the SIRT6 gene are not associated with human longevity. [ABSTRACT FROM AUTHOR]

In this study proteomics analysis was performed to investigate damage caused to ram sperm by the freeze-thaw process. Sperm motility, viability, reactive oxygen species (ROS) and adenosine triphosphate (ATP) content were measured to evaluate sperm quality. Compared with fresh groups, motility, viability and ATP content were all lower in freeze–thawed sperm (P < 0.001), and ROS content was higher (P < 0.001). Moreover, 25 differential protein spots were detected in two-dimensional gels using PDQuest 8.0 software and the corresponding proteins were identified using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF-TOF MS) coupled with searching of the NCBI protein sequence database. Among these proteins, hexokinase1 (HXK1), the enzyme that catalyzes the first step of glycolysis in the sperm glycolytic pathway, is known to be associated with sperm motility. Casein kinase II subunit alpha (CSNK2A2), a serine/threonine-selective protein kinase, is associated with sperm apoptosis. We used immunoblotting and immunofluorescence to analyze the expression and localization of these two proteins. HXK1 and CSNK2A2 expression levels in fresh sperm were significantly higher than that in freeze-thawed sperm (P < 0.001). HXK1 and CSNK2A2 were detected in the main part of the sperm flagellum, and the immunofluorescence signal from these proteins was weakened in the freeze-thawed group. Decreased expression of HXK1 and CSNK2A2 may be associated with decreased sperm motility and viability following freeze-thawing. [ABSTRACT FROM AUTHOR]

Abstract: Significant concerns have been raised over pollution of antibiotics including tetracyclines in aquatic environments in recent years. Graphene oxide (GO) is a potential effective absorbent for tetracycline antibiotics and can be used to remove them from aqueous solution. Tetracycline strongly deposited on the GO surface via π–π interaction and cation–π bonding. The adsorption isotherm fits Langmuir and Temkin models well, and the theoretical maximum of adsorption capacity calculated by Langmuir model is 313mgg−1, which is approximately in a close agreement with the measured data. The kinetics of adsorption fits pseudo-second-order model perfectly, and it has a better rate constant of sorption (k), 0.065gmg−1 h−1, than other adsorbents. The adsorption capacities of tetracycline on GO decreased with the increase in pH or Na+ concentration. The adsorption isotherms of oxytetracycline and doxycycline on GO were discussed and compared. [Copyright &y& Elsevier]

Orlistat (Xenical™), a US Food and Drug Administration (FDA)-approved anti-obesity drug, shows efficacy against multiple tumor types, including hepatocellular carcinoma (HCC), due to its ability to inhibit fatty acid synthase (FASN) activity. However, whether orlistat affects hepatocellular malignant transformation during hepatocarcinogenesis in vivo is unknown. This study assessed the antisteatotic and antitumorigenic efficacy of orlistat in a rapid HCC FVB/N mouse model established via hydrodynamic transfection of activated forms of AKT and c-Met proto-oncogenes. Human hepatoma cell lines were used for mechanical validation in vitro. Hematoxylin and eosin staining, immunohistochemistry, and immunoblotting were applied for the mechanistic investigation. The results revealed that when orlistat was administered in the early stage of AKT/c-Met-triggered hepatocarcinogenesis, it resulted in the elimination of hepatic tumor burden. Mechanistically, orlistat efficiently elevated PTEN expression and suppressed AKT/SREBP1/FASN signaling both in vivo and in vitro , impairing AKT/c-Met-driven de novo lipogenesis and aberrant proliferation. Altogether, this study demonstrates the antilipogenic and antiproliferative efficacy of orlistat in hepatocarcinogenesis, suggesting that orlistat may be beneficial for the treatment of HCC, especially in NAFLD-related HCCs featuring activated AKT/mTOR cascade and increased lipogenesis in livers. • FASN inhibitor orlistat delays AKT/c-Met-driven hepatocarcinogenesis in mice. • Orlistat attenuates hepatocellular malignant transformation in mice. • Orlistat elevates PTEN expression and inhibits AKT phosphorylation in the HCC mice. [ABSTRACT FROM AUTHOR]