ABSTRACT
OBJECTIVE: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics. METHODS: Four hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs). RESULTS: The functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages. Immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF. Metabolic disruption was significant in ACHD and severe in ACLF. The analysis of 62 overlapping DEGs further linked the HBV-based immune-metabolism disorder to ACLF progression. The signatures of interferon-related, neutrophil-related and monocyte-related pathways related to the innate immune response were significantly upregulated. Signatures linked to the adaptive immune response were downregulated. Disruptions of lipid and fatty acid metabolism were observed during ACLF development. External validation of four DEGs underlying the aforementioned molecular mechanism in patients and experimental rats confirmed their specificity and potential as biomarkers for HBV-ACLF pathogenesis. CONCLUSIONS: This study highlights immune-metabolism disorder triggered by HBV exacerbation as a potential mechanism of HBV-ACLF and may indicate a novel diagnostic and treatment target to reduce HBV-ACLF-related mortality.
Subject(s)
Acute-On-Chronic Liver Failure/pathology , Hepatitis B, Chronic/complications , Leukocytes, Mononuclear/immunology , Acute-On-Chronic Liver Failure/virology , Adaptive Immunity , Adult , Animals , Case-Control Studies , DNA, Viral/blood , Female , Hepatitis B virus , Humans , Immunity, Innate , Male , Metabolome , Middle Aged , Prospective Studies , Rats , TranscriptomeABSTRACT
Rhenium is one of the most valuable elements found in nature, and its capture and recycle are highly desirable for resource recovery. However, the effective and efficient collection of this material from industrial waste remains quite challenging. Herein, a tetraphenylmethane-based cationic polymeric network (CPN-tpm) nanotrap is designed, synthesized, and evaluated for ReO4- recovery. 3D building units are used to construct imidazolium salt-based polymers with positive charges, which yields a record maximum uptake capacity of 1133 mg g-1 for ReO4- collection as well as fast kinetics ReO4- uptake. The sorption equilibrium is reached within 20 min and a kd value of 8.5 × 105 mL g-1 is obtained. The sorption capacity of CPN-tpm remains stable over a wide range of pH values and the removal efficiency exceeds 60% for pH levels below 2. Moreover, CPN-tpm exhibits good recyclability for at least five cycles of the sorption-desorption process. This work provides a new route for constructing a kind of new high-performance polymeric material for rhenium recovery and rhenium-contained industrial wastewater treatment.
Subject(s)
Rhenium , Anions , Polymers , WastewaterABSTRACT
BACKGROUND & AIMS: The evaluation of the stage of liver fibrosis is essential in patients with chronic liver disease. However, due to the low quality of ultrasound images, the non-invasive diagnosis of liver fibrosis based on ultrasound images is still an outstanding question. This study aimed to investigate the diagnostic accuracy of a deep learning-based method in ultrasound images for liver fibrosis staging in multicentre patients. METHODS: In this study, we proposed a novel deep learning-based approach, named multi-scale texture network (MSTNet), to assess liver fibrosis, which extracted multi-scale texture features from constructed image pyramid patches. Its diagnostic accuracy was investigated by comparing it with APRI, FIB-4, Forns and sonographers. Data of 508 patients who underwent liver biopsy were included from 4 hospitals. The area-under-the ROC curve (AUC) was determined by receiver operating characteristics (ROC) curves for significant fibrosis (≥F2) and cirrhosis (F4). RESULTS: The AUCs (95% confidence interval) of MSTNet were 0.92 (0.87-0.96) for ≥F2 and 0.89 (0.83-0.95) for F4 on the validation group, which significantly outperformed APRI, FIB-4 and Forns. The sensitivity and specificity of MSTNet (85.1% (74.5%-92.0%) and 87.6% (78.0%-93.6%)) were better than those of three sonographers in assessing ≥F2. CONCLUSIONS: The proposed MSTNet is a promising ultrasound image-based method for the non-invasive grading of liver fibrosis in patients with chronic HBV infection.
Subject(s)
Elasticity Imaging Techniques , Liver Diseases , Aspartate Aminotransferases , Biomarkers , Biopsy , Hepatitis B virus , Humans , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/pathology , Liver Diseases/pathology , ROC CurveABSTRACT
BACKGROUND: Serum chitinase-3-like protein 1 (CHI3L1) is a potential biomarker for fibrosis assessment. We aimed to evaluate serum CHI3L1 as a noninvasive diagnostic marker for chronic hepatitis B virus-related fibrosis. METHODS: Serum CHI3L1 levels were measured by ELISA in 134 chronic hepatitis B (CHB) patients. Significant fibrosis was defined as a liver stiffness >â¯9.7 kPa. The performance of CHI3L1 was assessed and compared to that of other noninvasive tests by receiver operating characteristic (ROC) analysis. RESULTS: Serum CHI3L1 levels were significantly higher in CHB patients with significant hepatic fibrosis (≥â¯F2, 81.9 ng/mL) than in those without significant hepatic fibrosis (<â¯F2, 56.5 ng/mL) (Pâ¯<â¯0.001). In CHB patients, the specificity and sensitivity of CHI3L1 for predicting significant fibrosis were 75.6% and 59.1%, respectively, with a cut-off of 76.0 ng/mL and an area under the ROC curve of 0.728 (95% CI: 0.637-0.820). CONCLUSIONS: Serum CHI3L1 levels could be an effective new serological biomarker for the diagnosis of liver. Moreover, CHI3L1 is feasible in monitoring disease progression.
Subject(s)
Chitinase-3-Like Protein 1/blood , Hepatitis B, Chronic/blood , Liver Cirrhosis/blood , Adult , Biomarkers/blood , China , Disease Progression , Female , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/diagnosis , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/etiology , Male , Middle Aged , Severity of Illness IndexABSTRACT
BACKGROUND: Patients with hepatitis B-related acute-on-chronic liver failure (HB-ACLF) may have an increased circulating microbial burden. This study aimed to assess circulating microbial load and composition and to explore the association between the circulating microbiome and both systemic inflammation (SI) and clinical outcome in HB-ACLF. METHODS: Plasma from 50 HB-ACLF patients, 23 healthy controls and 25 patients with compensated liver cirrhosis (C-LC) was analysed for chemokines/cytokines and bacterial DNA and further analysed by 16S rDNApyrosequencing. Linear discriminant analysis effect size (LEfSe) and inferred metagenomics analyses were performed. RESULTS: The circulating bacterial DNA was significantly increased in HB-ACLF patients compared to that in the control groups. The overall microbial diversity was significantly decreased in HB-ACLF patients. HB-ACLF patients were enriched with Moraxellaceae, Sulfurovum, Comamonas and Burkholderiaceae but were depleted in Actinobacteria, Deinococcus-Thermus, Alphaproteobacteria, Xanthomonadaceae and Enterobacteriaceae compared to controls. Network analysis revealed a direct positive correlation between Burkholderiaceae and chemokine IP-10 in HB-ACLF patients. The relative abundance of Prevotellaceae independently predicted 28-day mortality. Inferred functional metagenomics predicted an enrichment of bacteria with genes related to methane, alanine, aspartate, glutamate, pyrimidine, purine and energy metabolism. CONCLUSIONS: HB-ACLF patients display increased circulating microbial burden, altered microbiome composition and a shift in microbiome functionality. The alteration in circulating microbiota is associated with SI and clinical outcome in HB-ACLF.
Subject(s)
Acute-On-Chronic Liver Failure/blood , Hepatitis B, Chronic/blood , Liver Cirrhosis/blood , Microbiota , Acute-On-Chronic Liver Failure/microbiology , Acute-On-Chronic Liver Failure/mortality , Adult , Biomarkers/blood , Case-Control Studies , Cytokines/blood , DNA, Bacterial/blood , Female , Hepatitis B, Chronic/microbiology , Humans , Inflammation Mediators/blood , Liver Cirrhosis/microbiology , Male , Middle Aged , Predictive Value of TestsABSTRACT
AIM: Flare-ups of chronic hepatitis B can sometimes be severe and even progress to acute-on-chronic liver failure (ACLF), with high short-term mortality. A timely estimation of the risk of death should be initiated early. The aim of the present study was to determine whether novel biomarkers add prognostic information beyond current clinical scoring systems. METHODS: Patients with hepatitis B-associated ACLF were prospectively enrolled from five hospitals in China between August 2017 and March 2018. Their plasma was screened for soluble CD163 (sCD163), neutrophil gelatinase-associated lipocalin (NGAL), and copeptin. The association between these biomarkers and mortality was analyzed. The performance of the Model for End-stage Liver Disease, Asian-Pacific Association for the Study of the Liver-ACLF Research Consortium score, and the Chronic Liver Failure Consortium ACLF score, with or without biomarkers, were compared. RESULTS: One hundred fifty one patients were enrolled. Advanced ACLF patients had significantly higher levels than early ACLF individuals of plasma biomarkers sCD163 (P = 0.001), NGAL (P = 0.006), and copeptin (P = 0.049). Thirty-four deaths occurred during the 28-day follow-up period (22.5%). Both sCD163 and NGAL showed a strong independent association with 28-day mortality, whereas copeptin did not. Scoring systems incorporating sCD163 and NGAL had better discrimination and calibration, as measured by area under the receiver operating characteristic curves, the Akaike information criteria, integrated discrimination improvement, and net reclassification improvement. CONCLUSIONS: Soluble CD163 and NGAL are independently associated with short-term mortality in hepatitis B-associated ACLF. Use of a combination of sCD163 and NGAL improves prognostication.
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Overexpression of lysine specific demethylase 1 (LSD1) has been found in many cancers. New anticancer drugs targeting LSD1 have been designed. The research on irreversible LSD1 inhibitors has entered the clinical stage, while the research on reversible LSD1 inhibitors has progressed slowly so far. In this study, 41 stilbene derivatives were studied as reversible inhibitors by three-dimensional quantitative structure-activity relationship (3D-QSAR). Comparative molecular field analysis (CoMFA q 2 = 0.623, r 2 = 0.987, r pred 2 = 0.857) and comparative molecular similarity indices analysis (CoMSIA q 2 = 0.728, r 2 = 0.960, r pred 2 = 0.899) were used to establish the model, and the structure-activity relationship of the compounds was explained by the contour maps. The binding site was predicted by two different kinds of software, and the binding modes of the compounds were further explored. A series of key amino acids Val288, Ser289, Gly314, Thr624, Lys661 were found to play a key role in the activity of the compounds. Molecular dynamics (MD) simulations were carried out for compounds 04, 17, 21, and 35, which had different activities. The reasons for the activity differences were explained by the interaction between compounds and LSD1. The binding free energy was calculated by molecular mechanics generalized Born surface area (MM/GBSA). We hope that this research will provide valuable information for the design of new reversible LSD1 inhibitors in the future.
Subject(s)
Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Histone Demethylases/antagonists & inhibitors , Stilbenes/chemistry , Binding Sites , Molecular Dynamics Simulation , Protein Binding , Quantitative Structure-Activity RelationshipABSTRACT
OBJECTIVE: The definition of acute-on-chronic liver failure (ACLF) based on cirrhosis, irrespective of aetiology, remains controversial. This study aimed to clarify the clinicopathological characteristics of patients with hepatitis B virus-related ACLF (HBV-ACLF) in a prospective study and develop new diagnostic criteria and a prognostic score for such patients. DESIGN: The clinical data from 1322 hospitalised patients with acute decompensation of cirrhosis or severe liver injury due to chronic hepatitis B (CHB) at 13 liver centres in China were used to develop new diagnostic and prognostic criteria. RESULTS: Of the patients assessed using the Chronic Liver Failure Consortium criteria with the exception of cirrhosis, 391 patients with ACLF were identified: 92 with non-cirrhotic HBV-ACLF, 271 with cirrhotic HBV-ACLF and 28 with ACLF with cirrhosis caused by non-HBV aetiologies (non-HBV-ACLF). The short-term (28/90 days) mortality of the patients with HBV-ACLF were significantly higher than those of the patients with non-HBV-ACLF. Total bilirubin (TB) ≥12 mg/dL and an international normalised ratio (INR) ≥1.5 was proposed as an additional diagnostic indicator of HBV-ACLF, and 19.3% of patients with an HBV aetiology were additionally diagnosed with ACLF. The new prognostic score (0.741×INR+0.523×HBV-SOFA+0.026×age+0.003×TB) for short-term mortality was superior to five other scores based on both discovery and external validation studies. CONCLUSIONS: Regardless of the presence of cirrhosis, patients with CHB, TB ≥12 mg/dL and INR ≥1.5 should be diagnosed with ACLF. The new criteria diagnosed nearly 20% more patients with an HBV aetiology with ACLF, thus increasing their opportunity to receive timely intensive management.
Subject(s)
Acute-On-Chronic Liver Failure/diagnosis , Hepatitis B, Chronic/diagnosis , Acute-On-Chronic Liver Failure/etiology , Acute-On-Chronic Liver Failure/microbiology , Acute-On-Chronic Liver Failure/mortality , Adult , Bilirubin/blood , Biomarkers/blood , China/epidemiology , Female , Hepatitis B, Chronic/mortality , Humans , International Normalized Ratio , Liver Cirrhosis/complications , Liver Cirrhosis/mortality , Male , Middle Aged , Prognosis , Prospective Studies , Severity of Illness IndexABSTRACT
OBJECTIVE: Stem cell transplantation provides a promising alternative for the treatment of fulminant hepatic failure (FHF). However, it lacks fundamental understanding of stem cells' activities. Our objective was to clarify stem cell-recipient interactions for overcoming barriers to clinical application. DESIGN: We used an in-house large-animal (pig) model of FHF rescue by human bone marrow mesenchymal stem cells (hBMSCs) and profiled the cells' activities. The control and transplantation groups of pigs (n=15 per group) both received a D-galactosamine (D-Gal) injection (1.5â g/kg). The transplantation group received hBMSCs via intraportal vein infusion (3×106 cells/kg) immediately after D-Gal administration. The stem cell-recipient interactions were quantitatively evaluated by biochemical function, cytokine array, metabolite profiling, transcriptome sequencing and immunohistochemistry. RESULTS: All pigs in the control group died within an average of 3.22â days, whereas 13/15 pigs in the transplantation group lived >14â days. The cytokine array and metabolite profiling analyses revealed that hBMSC transplantation suppressed D-Gal-induced life-threatening cytokine storms and stabilised FHF within 7â days, while human-derived hepatocytes constituted only â¼4.5% of the pig hepatocytes. The functional synergy analysis of the observed profile changes indicated that the implanted hBMSCs altered the pigs' cytokine responses to damage through paracrine effects. Delta-like ligand 4 was validated to assist liver restoration in both pig and rat FHF models. CONCLUSIONS: Our results delineated an integrated model of the multifaceted interactions between stem cells and recipients, which may open a new avenue to the discovery of single molecule-based therapeutics that simulate stem cell actions.
Subject(s)
Bone Marrow Transplantation , Cytokines/blood , Intracellular Signaling Peptides and Proteins/metabolism , Liver Failure, Acute/metabolism , Liver Failure, Acute/therapy , Membrane Proteins/metabolism , Mesenchymal Stem Cell Transplantation , Animals , Disease Models, Animal , Galactosamine/pharmacology , Hepatocytes , Humans , Liver/pathology , Liver Failure, Acute/pathology , Male , Paracrine Communication , Rats , Rats, Sprague-Dawley , Survival Rate , SwineABSTRACT
BACKGROUND The complete blood count (CBC) is the most common examination used to monitor overall health in clinical practice. Whether there is a relationship between CBC indexes and alanine transaminase (ALT) and aspartate aminotransferase (AST) has been unclear. MATERIAL AND METHODS In this study, 572 normal-weight and 346 overweight Chinese subjects were recruited. The relationship between CBC indexes with ALT and AST were analyzed by Pearson and Spearman correlations according to their sex, then we conducted colinearity diagnostics and multiple linear regression (MLR) analysis. A prediction model was developed by a back-propagation artificial neural network (BP-ANN). RESULTS ALT was related to 4 CBC indexes in the male normal-weight group and 3 CBC indexes in the female group. In the overweight group, ALT had a similar relationship with the normal group, but there was only 1 index related with AST in the normal-weight group and male overweight groups. The ALT regression models were developed in normal-weight and overweight people, which had better correlation coefficient (R>0.3). After training 1000 epochs, the BP-ANN models of ALT achieved higher correlations than MLR models in normal-weight and overweight people. CONCLUSIONS ALT is a more suitable index than AST for developing a regression model. ALT can be predicted by CBC indexes in normal-weight and overweight individuals based on a BP-ANN model, which was better than MLR analysis.
Subject(s)
Alanine Transaminase/blood , Asian People , Aspartate Aminotransferases/blood , Neural Networks, Computer , Adult , Blood Cell Count , Female , Humans , Male , Overweight/blood , Overweight/enzymology , Regression AnalysisABSTRACT
BACKGROUND: Serum quantitative hepatitis B surface antigen (HBsAg) levels may be an important predictor of hepatitis B e antigen (HBeAg) seroconversion (SC) in HBeAg-positive chronic hepatitis B (CHB) patients during antiviral treatment. The pattern of HBsAg variation in CHB patients either with or without SC following tenofovir disoproxil fumarate (TDF) treatment is not clearly understood. METHODS: Twenty patients with full experimental data were enrolled, and liver biochemistry, serum HBV DNA, and circulating CD4+CD25+ regulatory T cell (Treg) levels were determined at baseline and every 12 weeks after the initiation of TDF treatment (for a total of 96 weeks). In addition, the relationship between HBsAg or HBeAg and alanine aminotransferase (ALT), HBV DNA and Treg levels in SC and non-SC patients was analyzed. RESULTS: In all, 9 patients had undergone HBeAg seroconversion by week 72 of TDF treatment, and biochemical and virological indexes and Treg percentages declined to normal levels. Furthermore, the positive correlation between HBsAg and ALT, HBV DNA and Treg levels was significant for SC patients, but not for non-SC patients. However, for HBeAg, significant positive correlations were or not observed for both SC and non-SC patients. CONCLUSIONS: The quantitation of HBsAg is a more useful indicator than HBeAg for distinguishing SC and non-SC patients during TDF treatment. Moreover, HBsAg may be related to immune regulatory property of CHB patients during antiviral treatment.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/drug therapy , Adult , DNA, Viral/blood , Female , Hepatitis B virus/genetics , Hepatitis B, Chronic/immunology , Humans , MaleABSTRACT
For the sluggish reaction kinetics due to a four-electron transfer process, water oxidation is always a major obstacle to solar splitting of water to hydrogen. It remains a tough challenge to develop efficient nonnoble-metal photocatalysts for water oxidation. Herein, we decorate the host photocatalyst of Bi11VO19 nanotubes with the coatalyst of subnanometer MoOx clusters (denoted as Bi11VO19/MoOx hetero-nanotubes) via a one-step cation-exchange solvothermal reaction using Na2V6O16 nanowires as the hard template. It is observed that the morphology and microstructure of Bi11VO19/MoOx hetero-nanotubes vary with the dosage of Mo source and polyvinylpyrrolidone, as well as with the solvent composition. The optimized Bi11VO19/MoOx hetero-nanotubes significantly enhance the photooxidation of water to oxygen with visible light, delivering an oxygen production rate of 790â µmol g-1 h-1, which is 12â times that of bare Bi11VO19 nanotubes. In situ X-ray photoelectron spectroscopy and (photo)electrochemical characterization suggest that the enhanced photoactivity may be caused by the decorated cocatalyst of MoOx clusters, which extracts electrons from Bi11VO19 nanotubes, leaving an abundance of holes for water photooxidation. This work demonstrates a potential strategy to develop photocatalysts for energy conversion by constructing Bi11VO19-based nanostructures.
ABSTRACT
UNLABELLED: The effectiveness of human bone marrow mesenchymal stem cell (hBMSC) transplantation to treat acute and chronic liver injury has been demonstrated in animal models and in a few nonrandomized clinical trials. However, no studies have investigated hBMSC transplantation in the treatment of fulminant hepatic failure (FHF), especially in large animal (pig) models. The aim of this study was to demonstrate the safety, effectiveness, and underlying mechanism of hBMSC transplantation for treating FHF in pigs through the intraportal route. Human BMSCs (3 × 10(7) ) were transplanted into pigs with FHF via the intraportal route or peripheral vein immediately after D-galactosamine injection, and a sham group underwent intraportal transplantation (IPT) without cells (IPT, peripheral vein transplantation [PVT], and control groups, respectively, n = 15 per group). All of the animals in the PVT and control groups died of FHF within 96 hours. In contrast, 13 of 15 animals in the IPT group achieved long-term survival (>6 months). Immunohistochemistry demonstrated that transplanted hBMSC-derived hepatocytes in surviving animals were widely distributed in the hepatic lobules and the liver parenchyma from weeks 2 to 10. Thirty percent of the hepatocytes were hBMSC-derived. However, the number of transplanted cells decreased significantly at week 15. Only a few single cells were scattered in the regenerated liver lobules at week 20, and the liver tissues exhibited a nearly normal structure. CONCLUSION: Immediate IPT of hBMSCs is a safe and effective treatment for FHF. The transplanted hBMSCs may quickly participate in liver regeneration via proliferation and transdifferentiation into hepatocytes during the initial stage of FHF. This method can possibly be used in future clinical therapy.
Subject(s)
Liver Failure, Acute/mortality , Liver Failure, Acute/surgery , Mesenchymal Stem Cell Transplantation/methods , Animals , Humans , Male , Swine , Swine, MiniatureABSTRACT
Background: It is lacking that markers could predict the prognosis of chronic hepatitis B (CHB) subjects during antiviral treatment, and the related cellular immune mechanism is not fully evaluated. Aim: To explore the comprehensive profile of T cell receptor ß-chain (TRBV) and CD4+CD25+ regulatory T cell (Treg) in peripheral blood of CHB patients with HBeAg seroconverting (SC) during tenofovir disoproxil fumarate (TDF) treatment. Methods: The frequency of CD4+CD25high+ Treg and number of skewed TRBV in 20 HBeAg positive patients were determined at baseline and following every 12 weeks during 96-week TDF treatment. The relationship among serum alanine aminotransferase (ALT) level, HBV DNA load, Treg frequency, and the number of skewed TRBV, respectively, was analyzed for CHB patients. Receiver operative characteristic curve was applied to analyze their diagnostic value for HBeAg SC. Results: The number of skewed TRBV at week 48, Treg frequency at week 72, and ALT level at baseline could predict the HBeAg SC or non-SC in CHB patients during 96-week TDF treatment. Moreover, the positive correlation between ALT or HBV DNA and Treg levels or skewed TRBVs was significant in the SC group, but not in non-SC. Conclusions: The predictive cutoff value of ALT for HBeAg SC was 178 U/L at baseline. Moreover, the ALT, Treg, and TRBV families would be associated with the prognosis and pathogenesis of CHB patients during TDF treatment.
Subject(s)
Hepatitis B e Antigens , Hepatitis B, Chronic , Humans , Tenofovir/therapeutic use , Hepatitis B e Antigens/therapeutic use , DNA, Viral , T-Lymphocytes, Regulatory , Hepatitis B, Chronic/drug therapy , Antiviral Agents/therapeutic use , Viral Load , Treatment Outcome , Hepatitis B virus/geneticsABSTRACT
Histone deacetylases (HDACs) and lysine-specific demethylase 1 (LSD1) are attractive targets for epigenetic cancer therapy. There is an intimate interplay between the two enzymes. HDACs inhibitors have shown synergistic anticancer effects in combination with LSD1 inhibitors in several types of cancer. Herein, we describe the discovery of compound 5e, a highly potent HDACs inhibitor (HDAC1/2/6/8; IC50 = 2.07/4.71/2.40/107 nM) with anti-LSD1 potency (IC50 = 1.34 µM). Compound 5e exhibited marked antiproliferative activity in several cancer cell lines. 5e effectively induced mitochondrial apoptosis with G2/M phase arrest, inhibiting cell migration and invasion in MGC-803 and HCT-116 cancer cells. It also showed good liver microsomal stability and acceptable pharmacokinetic parameters in SD rats. More importantly, orally administered compound 5e demonstrated higher in vivo antitumor efficacy than SAHA in the MGC-803 (TGI = 71.5%) and HCT-116 (TGI = 57.6%) xenograft tumor models accompanied by good tolerability. This study provides a novel lead compound with dual inhibitory activity against HDACs and LSD1 to further develop epigenetic drugs for solid tumor therapy. Further optimization is needed to improve the LSD1 activity to achieve dual inhibitors with balanced potency on LSD1 and HDACs.
Subject(s)
Antineoplastic Agents , Histone Deacetylase Inhibitors , Humans , Rats , Animals , Histone Deacetylase Inhibitors/pharmacology , Cell Line, Tumor , Rats, Sprague-Dawley , Cell Proliferation , Apoptosis , Histone Demethylases , Antineoplastic Agents/pharmacology , Enzyme Inhibitors/pharmacology , Structure-Activity RelationshipABSTRACT
In this paper, the effect of different crystal forms of Al2O3 on fluoride removal was studied. All crystal forms of Al2O3 were based on the same boehmite precursor and were obtained using a hydrothermal and calcination method. γ-Al2O3 had higher fluoride removal performance (52.15â mg/g) compared with θ-Al2O3 and α-Al2O3. Density functional theory (DFT) calculations confirmed that fluoride removal was greatest for γ-Al2O3, followed by θ-Al2O3 and α-Al2O3, and γ-Al2O3 possessed the strongest fluoride binding energy (-3.93â eV). The typical adsorption behaviour was consistent with the Langmuir model and pseudo-second-order model, indicating chemical and monolayer adsorption. Different metal ions were used to modify γ-Al2O3, and lanthanum had the best effect. Lanthanum oxide was shown to play an important role in fluoride removal. The best La/Al doping ratio was 20â At%. The adsorption process of the composite was also consistent with chemical and monolayer adsorption. When the La/Al doping rate was 20%, the adsorption capacity reached 94.64â mg/g. Compared with γ-Al2O3 (1.39 × 10-7â m/s), the adsorption rate of 20La-Al2O3 was 3.93 × 10-7â m/s according to the mass transfer model. Furthermore, DFT was used to provide insight into the adsorption mechanism, which was mainly driven by electrostatic attraction and ion exchange.
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Heavy metal pollution is a serious threat to human health and the ecological environment, but adsorption technology based on nano adsorbents can effectively treat the crisis. However, due to the nanoscale effect, nano adsorbents have some crucial shortcomings, such as recycling difficulty and the loss of nanoparticles, which seriously limit their application. The feasible assembly of nano adsorbents is an accessible technology in urgent need of a breakthrough. In this study, three-dimensional (3D) adsorbent (MF/Ti3C2Tx/PmPD) with excellent performance and favorable recyclability was prepared by interfacial polymerization with melamine foam (MF) as the framework, two-dimensional (2D) titanium carbide (Ti3C2Tx) as the bridge and Poly (m-Phenylenediamine) (PmPD) as the active nano component. The morphology, structure, mechanical property of MF/Ti3C2Tx/PmPD and reference MF/PmPD were investigated through a scanning electron microscope (SEM), Fourier transformed infrared spectra (FT-IR), Raman scattering spectra and a pressure-stress test, respectively. Owning to the regulation of Ti3C2Tx on the morphology and structure of PmPD, MF/Ti3C2Tx/PmPD showed excellent adsorption capacity (352.15 mg/g) and favorable cycling performance. R-P and pseudo-second-order kinetics models could well describe the adsorption phenomenon, indicating that the adsorption process involved a composite process of single-layer and multi-layer adsorption and was dominated by chemical adsorption. In this research, the preparation mechanism of MF/Ti3C2Tx/PmPD and the adsorption process of Cr(VI) were systematically investigated, which provided a feasible approach for the feasible assembly and application of nano adsorbents in the environmental field.
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Capacitive deionization (CDI) is an emerging eco-friendly desalination technology with mild operation conditions. However, the energy consumption of CDI has not yet been comprehensively summarized, which is closely related to the economic cost. Hence, this study aims to review the energy consumption performances and mechanisms in the literature of CDI, and to reveal a future direction for optimizing the consumed energy. The energy consumption of CDI could be influenced by a variety of internal and external factors. Ion-exchange membrane incorporation, flow-by configuration, constant current charging mode, lower electric field intensity and flowrate, electrode material with a semi-selective surface or high wettability, and redox electrolyte are the preferred elements for low energy consumption. In addition, the consumed energy in CDI could be reduced to be even lower by energy regeneration. By combining the favorable factors, the optimization of energy consumption (down to 0.0089 Wh·gNaCl-1) could be achieved. As redox flow desalination has the benefits of a high energy efficiency and long lifespan (~20,000 cycles), together with the incorporation of energy recovery (over 80%), a robust future tendency of energy-efficient CDI desalination is expected.
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Electrochemical deionization (EDI) is hopefully the next generation of water treatment technology. Bismuth (Bi) is a promising anode material for EDI, due to its high capacity and selectivity toward Cl-, but the large volume expansion and severe pulverization aggressively attenuated the EDI cycling performance of Bi electrodes. Herein, carbon-layer-encapsulated nano-Bi composites (Bi@C) were prepared by a simple pyrolysis method using a Bi-based metal-organic framework as a precursor. Bi nanoparticles are uniformly coated within the carbon layer, in which the Bi-O-C bond enhances the interaction between Bi and C. Such a structure effectively relieves the stress caused by volume expansion by the encapsulation effect of the carbon layer. Moreover, the introduction of a carbon skeleton provides a conductive network. As a consequence, the Bi@C composite delivered excellent electrochemical performance with a capacity of 537.6 F g-1 at 1 mV s-1. The Cl- removal capacity was up to 133.5 mg g-1 at 20 mA g-1 in 500 mg L-1 NaCl solution. After 100 cycles, the Bi@C electrode still maintains 71.8% of its initial capacity, which is much higher than the 26.3% of the pure Bi electrode. This study provides a promising strategy for improving EDI electrode materials.
ABSTRACT
Bauxite is a widely available Al-O-rich mineral with great potential for abating fluoride. However, low adsorption capacity, a narrow workable pH range, and a lack of clarity on the best removal mechanism hinder its application. In this work, a highly efficient bauxite nanocomposite (Bx-Ce-La@500) was synthesized via doping and pyrolysis, and its fluoride adsorption in industrial wastewater was examined. Doping Ce/La synergistically improved the fluoride adsorption affinity of the composite (from pHPZC 8.0 ~ 10.0) and enhanced the â¢OH. The materials were characterized by SEM-EDS, BET, XRD, and TGA while XPS, FTIR, and DFT were used to investigate the mechanism of fluoride sorption. Results show that Bx-Ce-La@â¯500 has a positive zeta potential of 26.3-23.1â¯mV from pH 1~ 10. The Langmuir model was the best fit with a maximum adsorption capacity of 88.13â¯mg/g and removal efficiency up to 100% in 50â¯ppmâ¯F- solution. The high F- removal was attributed to the enhanced surface affinity and the formation of adequate â¢OH on the material. Except for carbonate and phosphate ions, other ions exhibited negligible effects and the selective removal of F- in real wastewater was high. The main mechanism of adsorption was the ligand/ion exchange and electrostatic attraction.