Thus, whereas the type I IFN receptor is ubiquitous, the type III IFN receptor is relatively restricted to epithelial cells, including hepatocytes. Importantly, it is only weakly (if at all) expressed by hemopoietic cells. Despite these differences,

the expression of types I and III IFN is elicited by similar stimuli (e.g. via stimulation of Toll-like receptors [TLR] responsive to viral products). Further, the types I and III IFN receptors share common downstream signaling pathways (Janus kinase—signal transducer and activator of transcription) to induce IFN-stimulated gene expression.60 Type III IFN inhibit HCV replication in vitro,60,61 as well as in vivo. This is thought to occur via the upregulation of key IFN-stimulated genes (ISG), including ISG15, MX1 (myxovirus resistance-1), and OAS (2′,5′-oligoadenylate synthetase-like http://www.selleckchem.com/products/PLX-4032.html gene), which interrupt HCV replication through processes that include the suppression of viral replication and protein synthesis.60–63

Type III IFN have also been shown to augment natural killer (NK) cell immunity and antigen-specific CD8+ T-cell cytotoxicity.64,65 Recently, increased NK cell inhibitory receptor expression has been associated with the poor-response IL28B genotype and treatment response.66 The role of IFN-λ, and specifically, IL28B, in HCV pathogenesis remains unclear. Furthermore, the biological click here consequence(s) of IL28B polymorphism is/are not known. There are two key questions: what is the causal variant, and what does it do? This is a fertile area for research, and the field is in its infancy. The functional variant responsible for the IL28B haplotype

association remains selleck screening library unclear. It is unlikely that any of the association tag SNPs are causal, and none are a good functional candidate. Potentially-functional polymorphisms have been identified that are in linkage with the discovery SNP. By sequencing the IL28B region in 96 patients, Ge et al. identified two candidate causal variants.3 One variant was a G > C transition, 37 base pairs upstream from the translation initiation codon (rs28416813), and the other was a non-synonymous SNP encoding an amino-acid substitution in exon 2 (rs8103142, Lys70Arg), which might potentially affect receptor binding or protein stability. These SNPs have also been identified on a common haplotype with rs12979860 in a second study by Di Iulio and colleagues.47 In both studies, the linkage disequilibrium between these SNPs and the discovery tag SNP was so strong that it was not possible for association testing to statistically differentiate which was more strongly associated with SVR. For this reason, it is likely that functional studies will be necessary. A number of studies have considered the relationship between the IL28B genotype and IFN-λ-3 mRNA expression.

As shown in Fig. 4, TRIM35 was observed to not only arrest the cell cycle at G2/M phase but also to promote cell apoptosis of HCC cells overexpressing TRIM35, indicating that one mechanism by which TRIM35 inhibits HCC cell Tyrosine Kinase Inhibitor Library price proliferation is through impeding the cell cycle progression or inducing apoptotic cell death. To further determine the clinicopathologic significance of TRIM35 in HCC, we performed immunohistochemical (IHC) analysis of TRIM35 in a tissue array that included an independent set of 207 paired

HCC and adjacent noncancerous tissues as well as 10 normal liver and 16 cirrhosis tissues. As shown in Fig. 5A,B, not only was the protein level of TRIM35 sharply decreased in HCC tissues compared with matched noncancerous Alectinib tissues, normal liver samples or cirrhosis tissues, but the proportion of HCC specimens with TRIM35 underexpression was also predominant, which is consistent with our genomic and transcriptional results (Fig. 5C,D). Importantly, the expression level of TRIM35 was negatively correlated with tumor grade, tumor size, and serum alpha-fetoprotein (AFP) level (Table 2). However, the down-regulation of TRIM35 expression has no significant correlation with overall survival of HCC patients (data not shown). Taken together, these results suggested that loss of TRIM35 expression is

a critical event in the development and progression of HCC. Copy number alterations represent a substantial category of genetic variations. During carcinogenesis, cancer genomes often acquire somatic copy number changes, which can alter the dosage of oncogenes and tumor suppressors.1 Although several previous selleck chemicals llc studies have applied copy number analyses for HCC,12-14 in the present study we mainly focused on identifying CNAs and their associated oncogenes and tumor suppressors in HCC genomes using high-resolution SNP 6.0 arrays, which can provide high sensitivity and specificity in detecting subtle CNAs. In

addition, we used 58 paired tumor and adjacent nontumor tissues from the same individuals, which allowed us to identify highly recurrent CNAs other than accidental CNAs in HCC. Chromosomal instability, including copy number gains or losses in genomic DNA, is commonly observed in HCC, and several aberrant chromosomal loci have been frequently reported in association with this disease.32 For example, a gain at 1q is one of the most frequently detected alterations in HCC (58%-86%) and has been suggested as an early genomic event in the process of HCC development, whereas a loss at 8p is well documented in HCC, with a frequency of 29% to 77%.14 However, there is little doubt that additional CNAs and targeted genes within these loci exist in HCC. In this study we identified a total of 1,241 significant regions of CNAs.

Histone hyperacetylation is associated with transcriptional activation. In addition, trimethylation of lysine 4 of histone 3 (H3K4me3) is a hallmark of actively transcribed genes, whereas H3K9 dimethylation (H3K9me2) is typically found in heterochromatin AZD5363 and silenced genes. Remarkably, we found that BAF60a expression led to a robust increase in histone H3 acetylation and H3K4me3 levels with a corresponding

reduction in H3K9me2 levels on the proximal Bmal1 promoter. These results indicate that BAF60a activates Bmal1 transcription by altering the local chromatin environment from a repressive to an active state. Finally, to exclude the possibility that the SWI/SNF Osimertinib manufacturer complex in HepG2 or HEK293 cells we used in our experiments might not include BAF60a as the major component and the effects of BAF60a we observed here were actually exaggerated by the strong exogenous expression, we compared the endogenous expression levels of BAF60a, BAF60b, and BAF60c in these cell types. Semiquantitative RT-PCR revealed that the mRNA abundance of BAF60a was quite similar to that of

BAF60b, but significantly higher than that of BAF60c (Supporting Fig. 4). RORα has been reported to regulate G6Pase transcription through binding to the RORE element on the G6Pase promoter.28 Therefore, we hypothesized that RORα may serve as a partner for BAF60a to regulate metabolic genes including G6Pase. Indeed, BAF60a and RORα robustly increased the transcriptional activity of G6Pase promoter and endogenous G6Pase gene expression (Fig. 5A,B). Similar to the observations in Bmal1 transcription, the RORE region in G6Pase promoter was essential for the synergistic activation of BAF60a and RORα, which could be negatively regulated by Rev-erb orphan receptors (Fig. 5C). In addition, BAF60a could also lose the compact structure of chromatin in which the proximal G6Pase promoter locates (Fig. 5D; Supporting

Fig. selleck products 5). Finally and functionally, BAF60a increased the glucose production rate in mouse primary hepatocytes (Fig. 5E). We monitored BAF60a mRNA levels throughout a day in long-period ClockΔ19 and Over-time mice and in short-period Per2 knockout mice. As shown in Fig. 6, the rhythmic expression pattern of BAF60a mRNA was disrupted in all these animals, indicating that BAF60a is conversely subjected to the circadian feedback control. The SWI/SNF complexes have been implicated in the regulation of key cellular processes, including embryogenesis, cell cycle, differentiation, and tumorigenesis.29-31 In this report, we identify one member, BAF60a, of this family as a circadian clock transcriptional output in mammalian liver. BAF60a was initially identified as a determinant of the transactivation potential of Fos/Jun dimers to induce the endogenous AP-1-regulated genes such as collagenase and c-met.

The patient also requires consistent access to the care in real time. It is also important that there is an appropriate and regular forum to discuss patient care plans with input Belnacasan from the team members especially when a management plan is complex, has different alternatives and/or when the approach is controversial. To ensure functionality and success of the multidisciplinary care programme, the delivery of care must operate through reliable and dependable means of communication and clear documentary procedure. Finally, any such clinic requires solid administrative support and requires constant re-evaluation of its ability to deliver sound and secure care for women with IBD to ensure

its success over time. The role of the nurse coordinator in the multidisciplinary care of women with IBD is pivotal. The nurse, who is likely to be working

at an advanced practice level or with significant experience in the specialist area, is often the first point of contact for women who may be experiencing ongoing menorrhagia or other gynaecological symptoms, not resolved by visits to her general practitioner, GSK2118436 or for those who are planning pregnancy or are newly pregnant and seeking advice about their obstetric care. The multidisciplinary approach to managing these women may involve many health care professionals as already described, and the haemophilia nurse is best placed to coordinate appropriate hospital visits and to facilitate the woman to attend as few visits as possible. For those presenting with menorrhagia or other gynaecological symptoms, haemophilia

nurses should check details have the skills and knowledge to take a gynaecological history, to assess the main symptoms and to order the appropriate investigations, including blood tests and a pelvic ultrasound scan, in advance of the woman’s appointment in the multidisciplinary clinic. Teaching a woman to use the pictorial blood assessment chart (PBAC) [8] and to bring the completed chart to her clinic appointment offers a guide to the extent of menorrhagia. This coupled with the results of the investigations ensures that decision-making regarding treatment options, including medical management or the need for surgical investigations or interventions can take place at the first visit to the clinic [9]. The haemophilia nurse is able to offer regular monitoring of the outcomes of interventions in an ongoing relationship with the woman [10]. This does not necessarily have to involve visits to the haemophilia centre. Continued encouragement and education of affected women regarding evaluation of any medical/surgical interventions using the PBAC can be continued by telephone or mail. Lack of improvement in symptoms needs to be explored, as compliance with prescribed treatments is vital for the best possible outcomes.

And DES might be a cause of the symptom in FH patients. Key Word(s): 1. motility disorders; 2. functional heartburn; 3. weakly acid NERD; 4. HRM; Group % WAR (a) AR (b) FH (c) P value N = 36 N = 46 N = 21 (chi-square test) 52 ± 12 yr 52 ± 15 yr 51 ± 11 yr   Weak peristalsis 61.1 (22/36) 37.0 (17/46) 23.8 (5/21) a/b, p = 0.045; a/c, p = 0.028 Large breaks 36.1 (13/36) 23.9 (11/46) 19.4 (4/21) NS Small breaks 25 (9/36) 13.4 (6/46) 4.8 (1/21) a/b, p = 0.018; a/c, p = 0.010 Normal 36.1 (13/36) 45.7 (21/46) 38.1 (8/21) NS Rapid contractions 2.8 (1/36)

4.3 (2/46) 14.3 (3/21) NS Distal esophagea lspasm (DES) 0 6.5(3/46) 14.3 (3/21) a/c, p = 0.045 EGJ outflow obstruction 0 4.3(2/46) 9.5 (2/21) NS Jackhammer PD0325901 nmr 0 2.2(1/46) 0 NS Presenting Author: PEYMAN ADIBI Additional Authors: HAMID REZA MARATEB, MARJAN MANSOURIAN, HAMED DAGHAGHZADEH, AMMAR HASSANZADEH KESHTELI, NIKOLAOS ANDRIKOS, SOBHAN GOUDARZI Corresponding Author: HAMID REZA MARATEB Affiliations: University of Isfahan; Isfahan University of Medical Sciences; Isfahan University of Medical Sciences; University of Alberta; Politecnico di Torino Objective: Functional gastrointestinal disorders (FGIDs) are widespread cause of considerable social

and economic burden. One of the aims of the SEPAHAN project was to assess the prevalence of different FGIDs within an Iranian population of GDC-0449 in vivo 6239 adults find more in a cross-sectional study. Accurate data interpretation requires diagnosis and classification of FGIDs that implies clustering the rank-data

questionnaires. Methods: The aim of clinical clustering is to assign objects into groups with similar disorders. In SEPAHAN project, each cluster could be related to an FGID whose inputs are four-item rating scales of 37 selected head-questions. Methods such as (fuzzy) k-mode, hamming distance (HD) vectors, clustering categorical data via maximal K-partite cliques (CLICK), robust hierarchical clustering (ROCK), median fuzzy c-means were not successful either because of the sensitivity to some tuning parameters and (or) unreliable clinical validity assessment. However, our proposed method which is an ordinal to interval data conversion, following a modified OPTICS (ordering points to identify the clustering structure) showed acceptable results. Results: The output clustering structure is shown in Figure 1. Each plateau could be considered as a candidate FGID, whose representative shows the corresponding dominant symptoms. A total of 25 clusters were detected. The minimum number of subjects in each category was set to (n_min = 50). Conclusion: We have proposed a clustering of the SEPAHAN project which, unlike other clustering methods, is very fast (single-pass), ordinal, and only requires one tuning parameter (n_min).

And DES might be a cause of the symptom in FH patients. Key Word(s): 1. motility disorders; 2. functional heartburn; 3. weakly acid NERD; 4. HRM; Group % WAR (a) AR (b) FH (c) P value N = 36 N = 46 N = 21 (chi-square test) 52 ± 12 yr 52 ± 15 yr 51 ± 11 yr   Weak peristalsis 61.1 (22/36) 37.0 (17/46) 23.8 (5/21) a/b, p = 0.045; a/c, p = 0.028 Large breaks 36.1 (13/36) 23.9 (11/46) 19.4 (4/21) NS Small breaks 25 (9/36) 13.4 (6/46) 4.8 (1/21) a/b, p = 0.018; a/c, p = 0.010 Normal 36.1 (13/36) 45.7 (21/46) 38.1 (8/21) NS Rapid contractions 2.8 (1/36)

4.3 (2/46) 14.3 (3/21) NS Distal esophagea lspasm (DES) 0 6.5(3/46) 14.3 (3/21) a/c, p = 0.045 EGJ outflow obstruction 0 4.3(2/46) 9.5 (2/21) NS Jackhammer selleck screening library 0 2.2(1/46) 0 NS Presenting Author: PEYMAN ADIBI Additional Authors: HAMID REZA MARATEB, MARJAN MANSOURIAN, HAMED DAGHAGHZADEH, AMMAR HASSANZADEH KESHTELI, NIKOLAOS ANDRIKOS, SOBHAN GOUDARZI Corresponding Author: HAMID REZA MARATEB Affiliations: University of Isfahan; Isfahan University of Medical Sciences; Isfahan University of Medical Sciences; University of Alberta; Politecnico di Torino Objective: Functional gastrointestinal disorders (FGIDs) are widespread cause of considerable social

and economic burden. One of the aims of the SEPAHAN project was to assess the prevalence of different FGIDs within an Iranian population of 17-AAG in vivo 6239 adults click here in a cross-sectional study. Accurate data interpretation requires diagnosis and classification of FGIDs that implies clustering the rank-data

questionnaires. Methods: The aim of clinical clustering is to assign objects into groups with similar disorders. In SEPAHAN project, each cluster could be related to an FGID whose inputs are four-item rating scales of 37 selected head-questions. Methods such as (fuzzy) k-mode, hamming distance (HD) vectors, clustering categorical data via maximal K-partite cliques (CLICK), robust hierarchical clustering (ROCK), median fuzzy c-means were not successful either because of the sensitivity to some tuning parameters and (or) unreliable clinical validity assessment. However, our proposed method which is an ordinal to interval data conversion, following a modified OPTICS (ordering points to identify the clustering structure) showed acceptable results. Results: The output clustering structure is shown in Figure 1. Each plateau could be considered as a candidate FGID, whose representative shows the corresponding dominant symptoms. A total of 25 clusters were detected. The minimum number of subjects in each category was set to (n_min = 50). Conclusion: We have proposed a clustering of the SEPAHAN project which, unlike other clustering methods, is very fast (single-pass), ordinal, and only requires one tuning parameter (n_min).

And DES might be a cause of the symptom in FH patients. Key Word(s): 1. motility disorders; 2. functional heartburn; 3. weakly acid NERD; 4. HRM; Group % WAR (a) AR (b) FH (c) P value N = 36 N = 46 N = 21 (chi-square test) 52 ± 12 yr 52 ± 15 yr 51 ± 11 yr   Weak peristalsis 61.1 (22/36) 37.0 (17/46) 23.8 (5/21) a/b, p = 0.045; a/c, p = 0.028 Large breaks 36.1 (13/36) 23.9 (11/46) 19.4 (4/21) NS Small breaks 25 (9/36) 13.4 (6/46) 4.8 (1/21) a/b, p = 0.018; a/c, p = 0.010 Normal 36.1 (13/36) 45.7 (21/46) 38.1 (8/21) NS Rapid contractions 2.8 (1/36)

4.3 (2/46) 14.3 (3/21) NS Distal esophagea lspasm (DES) 0 6.5(3/46) 14.3 (3/21) a/c, p = 0.045 EGJ outflow obstruction 0 4.3(2/46) 9.5 (2/21) NS Jackhammer Selleckchem Doxorubicin 0 2.2(1/46) 0 NS Presenting Author: PEYMAN ADIBI Additional Authors: HAMID REZA MARATEB, MARJAN MANSOURIAN, HAMED DAGHAGHZADEH, AMMAR HASSANZADEH KESHTELI, NIKOLAOS ANDRIKOS, SOBHAN GOUDARZI Corresponding Author: HAMID REZA MARATEB Affiliations: University of Isfahan; Isfahan University of Medical Sciences; Isfahan University of Medical Sciences; University of Alberta; Politecnico di Torino Objective: Functional gastrointestinal disorders (FGIDs) are widespread cause of considerable social

and economic burden. One of the aims of the SEPAHAN project was to assess the prevalence of different FGIDs within an Iranian population of Angiogenesis antagonist 6239 adults learn more in a cross-sectional study. Accurate data interpretation requires diagnosis and classification of FGIDs that implies clustering the rank-data

questionnaires. Methods: The aim of clinical clustering is to assign objects into groups with similar disorders. In SEPAHAN project, each cluster could be related to an FGID whose inputs are four-item rating scales of 37 selected head-questions. Methods such as (fuzzy) k-mode, hamming distance (HD) vectors, clustering categorical data via maximal K-partite cliques (CLICK), robust hierarchical clustering (ROCK), median fuzzy c-means were not successful either because of the sensitivity to some tuning parameters and (or) unreliable clinical validity assessment. However, our proposed method which is an ordinal to interval data conversion, following a modified OPTICS (ordering points to identify the clustering structure) showed acceptable results. Results: The output clustering structure is shown in Figure 1. Each plateau could be considered as a candidate FGID, whose representative shows the corresponding dominant symptoms. A total of 25 clusters were detected. The minimum number of subjects in each category was set to (n_min = 50). Conclusion: We have proposed a clustering of the SEPAHAN project which, unlike other clustering methods, is very fast (single-pass), ordinal, and only requires one tuning parameter (n_min).

Due to the sample sizes and similar results found in initial analyses, the SVR, relapse, and breakthrough categories were combined to form the responder group in some analyses. Undetectable HCV RNA levels were defined as HCV RNA <28 IU/mL in one study (Roche High Pure System/COBAS TaqMan HCV Monitor

Test)8 and <50 IU/mL in three studies (Roche Amplicor polymerase chain reaction assay).1, 2, 7 Analyses were performed using the intent-to-treat population MLN0128 nmr that received at least one dose of study medication. Linear regression analysis was performed to test the null hypothesis that the mean maximum decrease was the same across virologic response categories. The maximum decrease was the dependent variable. Cirrhosis, an independent predictor of non-SVR, was included in the model if Gemcitabine in vitro it was significant (P

< 0.05). To account for the impact of drug exposure, total PEG-IFN received over the whole treatment duration and total ribavirin received per kilogram of baseline weight were included in the model. Per protocol, ribavirin dose was based on baseline weight and was not modified due to changes in weight during treatment. With the virologic response category forced into the model regardless of significance, the backward selection method was used to eliminate the covariates (cirrhosis and PEG-IFN and ribavirin exposures) that were not

significant (P > 0.05). Adjusted mean maximum decreases for SVR, relapse, breakthrough, and nonresponder were calculated using the least square means from the final models. A sensitivity analysis including only treatment completers was performed to take into consideration the duration of therapy. In addition, separate models were conducted using the same procedures with changes in pharmacodynamic parameters from baseline to weeks 4, 12, and 24 as dependent variables. In these models, the total dose received up to the corresponding selleck screening library time point was used in the analysis. The same procedures were also used to assess the effects of race/ethnicity on hematologic parameters and weight. The association between hemoglobin decline and SVR was assessed with and without adjustment for drug exposure using logistic regression models with SVR/non-SVR as the dependent variable. Table 1 presents the baseline demographic and clinical characteristics of 1,778 patients infected with HCV genotypes 1, 4, 5, or 6 from four randomized clinical trials of 24 or 48 weeks of treatment with PEG-IFN alfa-2a and ribavirin.

Due to the sample sizes and similar results found in initial analyses, the SVR, relapse, and breakthrough categories were combined to form the responder group in some analyses. Undetectable HCV RNA levels were defined as HCV RNA <28 IU/mL in one study (Roche High Pure System/COBAS TaqMan HCV Monitor

Test)8 and <50 IU/mL in three studies (Roche Amplicor polymerase chain reaction assay).1, 2, 7 Analyses were performed using the intent-to-treat population Nutlin 3a that received at least one dose of study medication. Linear regression analysis was performed to test the null hypothesis that the mean maximum decrease was the same across virologic response categories. The maximum decrease was the dependent variable. Cirrhosis, an independent predictor of non-SVR, was included in the model if PS-341 in vivo it was significant (P

< 0.05). To account for the impact of drug exposure, total PEG-IFN received over the whole treatment duration and total ribavirin received per kilogram of baseline weight were included in the model. Per protocol, ribavirin dose was based on baseline weight and was not modified due to changes in weight during treatment. With the virologic response category forced into the model regardless of significance, the backward selection method was used to eliminate the covariates (cirrhosis and PEG-IFN and ribavirin exposures) that were not

significant (P > 0.05). Adjusted mean maximum decreases for SVR, relapse, breakthrough, and nonresponder were calculated using the least square means from the final models. A sensitivity analysis including only treatment completers was performed to take into consideration the duration of therapy. In addition, separate models were conducted using the same procedures with changes in pharmacodynamic parameters from baseline to weeks 4, 12, and 24 as dependent variables. In these models, the total dose received up to the corresponding learn more time point was used in the analysis. The same procedures were also used to assess the effects of race/ethnicity on hematologic parameters and weight. The association between hemoglobin decline and SVR was assessed with and without adjustment for drug exposure using logistic regression models with SVR/non-SVR as the dependent variable. Table 1 presents the baseline demographic and clinical characteristics of 1,778 patients infected with HCV genotypes 1, 4, 5, or 6 from four randomized clinical trials of 24 or 48 weeks of treatment with PEG-IFN alfa-2a and ribavirin.

1C). These data thus suggested that HBx may promote expansion of HPCs in DDC-treated mice. It has been shown that the EpCAM+ cells isolated from DDC liver have adult progenitor potential that possess the capacity for unlimited proliferation and bidirectional differentiation.18 Flow cytometric analysis of

nonparenchymal cells prepared from the liver of HBx mice fed with DDC for 1 month showed a higher percentage of EpCAM+CD45− HPCs (Fig. 1D). When cultured at low density, EpCAM+CD45− HPCs isolated from HBx mice were able to form more and larger colonies than EpCAM+CD45− PF-02341066 molecular weight cells from WT mice (Fig. 2A), suggesting that these cells may have a stronger stem-like property. To further determine the characteristics of HPCs, the gene expression profile of magnetic sorted primary EpCAM+CD45− cells (Supporting Figs. S1, S2) was examined by quantitative reverse-transcription polymerase chain reaction (RT-PCR). As shown in Fig. 2B, HPCs from HBx mice demonstrated stronger expression of stem/progenitor cell markers (EpCAM, CD133, CD90, ABCG2, AFP, and CK19) than those from WT controls. However,

there were no significant differences in the expression of the oncogenes (K-ras, N-ras) between HPCs from HBx and control WT mice at 1 and 2 months DDC treatment (Fig. 2B; Fig. S3). To evaluate the self-renewal ability of HPCs, we performed a sphere formation assay. Compared with WT control, more spheres were observed 3-deazaneplanocin A clinical trial in EpCAM+CD45− HPCs isolated from HBx mice (Fig. 2C). Recent evidence shows that DDC not only causes liver damage along with the proliferation

find more of HPCs, but also facilitates some oncogene-induced tumorigenesis in the adult liver.19 After consecutive administration of 0.1% DDC for 4 months, both HBx and WT mice showed an increase in liver size and toughness on the liver surface compared with livers from mice treated with DDC for 1 month (Fig. S4A,B). Histological and flow cytometric analysis revealed persistent HPC expansion in both groups, but more robust in HBx mice (Fig. 1C,D). HPCs from HBx mice also showed increased expression of stem/progenitor cell markers and stronger sphere formation ability compared with those from WT mice (Fig. 2B,C). Furthermore, the expression of the oncogenes (K-ras, N-ras) was up-regulated in HPCs from HBx mice (Fig. 2B), suggesting that HBx may also promote the HPCs to obtain transformed characteristics after long-term DDC treatment. To further observe whether long-term exposure to a DDC diet could induce tumors, HBx and WT mice were continuously fed a DDC diet for 5-7 months. As the results in Fig. 3A show, all HBx mice (n = 15) developed liver tumors after 7 months, whereas none of WT mice (n = 15) had any liver tumors. Interestingly, after 5 months DDC treatment, although some HBx did not develop liver tumors, GSTpi and GPC3-positive dysplastic nodules were detectable in their liver tissues (Fig. S4C,D).