User-Guided Deep Human Image Matting Using Arbitrary Trimaps.

Image matting is widely studied for accurate foreground extraction. Most algorithms, including deep-learning based solutions, require a carefully edited trimap. Recent works attempt to combine the segmentation stage and matting stage in one CNN model, but errors occurring at the segmentation stage lead to unsatisfactory matte. We propose a user-guided approach for practical human matting. More precisely, we provide a good automatic initial matting and a natural way of interaction that reduces the workload of drawing trimaps and allows users to guide the matting in ambiguous situation. We also combine the segmentation and matting stage in an end-to-end CNN architecture and introduce a residual-learning module to support convenient stroke-based interaction. The proposed model learns to propagate the input trimap and modify the deep image features, which can efficiently correct the segmentation errors. Our model supports arbitrary forms of trimaps from carefully edited to totally unknown maps. Our model also allows users to choose from different foreground estimations according to their preference. We collected a large human matting dataset consisting of 12K real-world human images with complex background and human-object relations. The proposed model is trained on the new dataset with a novel trimap generation strategy that enables the model to tackle different test situations and highly improves the interaction efficiency. Our method outperforms other state-of-the-art automatic methods and achieve competitive accuracy when high-quality trimaps are provided. Experiments indicate that our interactive matting strategy is superior to separately estimating the trimap and alpha matte using two models.

Relation of Mitral Leaflet Elongation to Nonsustained Ventricular Tachycardia in Patients with Obstructive Hypertrophic Cardiomyopathy.

The impact of mitral valve abnormality on the occurrence of non-sustained ventricular tachycardia (NSVT) in patients with hypertrophic cardiomyopathy (HC) has not been well determined. We sought to demonstrate the relation of mitral valve abnormalities with NSVT in patients with obstructive HC. Three hundred and sixteen adult patients with obstructive HC with at least 1 Holter electrocardiographic monitoring and cardiac magnetic resonance (CMR) from 2014 to 2018 were enrolled. CMR images and Holter electrocardiography were analyzed in all patients. NSVT occurred in 50 patients (16%). Compared with those without NSVT, anterior mitral leaflet and posterior mitral leaflet lengths was significantly increased in patients with NSVT (AML 32.0 ± 5.0mm vs. 26.1±4.8mm, p<0.001; PML 17.7±3.7mm vs. 15.2±2.7mm, p<0.001, respectively). Multivariate logistic regression analysis indicated that elongated AML and PML were significantly independent predictors of NSVT (AML: OR 1.261, 95%CI 1.156-1.375, p<0.001; PML: OR 1.126, 95%CI 1.001-1.265, p=0.047). Furthermore, the area under the receiver operating characteristic curve for AML was 0.812. At a cutoff valve of 27.5mm, AML length had a sensitivity of 86% and specificity of 65%. Elongated mitral leaflets independently correlated with NSVT in patients with obstructive HC. Furthermore, the morphological abnormalities of mitral valve could serve as a useful marker for improving risk stratification of SCD and may play a role in optimizing surgical strategy for patients with obstructive HC.

Prominent Structures for Video Analysis and Editing.

We present prominent structures in video, a representation of visually strong, spatially sparse and temporally stable structural units, for use in video analysis and editing. With a novel quality measurement of prominent structures in video, we develop a general framework for prominent structure computation, and an efficient hierarchical structure alignment algorithm between a pair of videos. The prominent structural unit map is proposed to encode both binary prominence guidance and numerical strength and geometry details for each video frame. Even though the detailed appearance of videos could be visually different, the proposed alignment algorithm can find matched prominent structure sub-volumes. Prominent structures in video support a wide range of video analysis and editing applications including graphic match-cut between successive videos, instant cut editing, finding transition portals from a video collection, structure-aware video re-ranking, visualizing human action differences, etc.

Expression profile of Toll­like receptors in human breast cancer.

Toll­like receptors (TLRs) are the most widely studied pattern recognition receptors. Mounting evidence suggests an important association between TLRs and the occurrence and development of breast cancer. Thus, targeting these receptors may be a potential strategy for breast cancer treatment. The current study analyzed the data of 1,215 patients with breast cancer obtained from The Cancer Genome Atlas (TCGA) database. It was observed that, in addition to TLR6, TLR7 and TLR8, the expression of the remaining TLRs in breast cancer tissues was lower than that in normal tissues. In addition, TLR3 and TLR9 displayed significantly different expression levels in ER­/PR­negative breast cancer compared with the control tissues, while TLR5 expression was significantly reduced in HER2­enriched breast cancer. Furthermore, TLR10 exhibited lower expression levels in advanced stages of the disease as compared with that observed in earlier stages. Survival analysis revealed that the expression of TLR4 and TLR7 had a significant impact on survival, and higher expression levels suggested worse prognosis. Finally, the expression levels of TLR1, TLR2, TLR4, TLR5, TLR6 and TLR10 were correlated with those of the inflammatory cytokines interleukin­1ß and tumor necrosis factor­α, while the expression levels of TLR3, TLR7, TLR8 and TLR9 were correlated with those of interferon­ß and C­X­C motif chemokine ligand 10. Taken together, the current study results suggest that TLR expression may serve as a biomarker of cancer pathogenesis and progression, and may provide new insights for the treatment of breast cancer through the regulation and targeting of TLRs.

Tunable magnetic and half-metallic properties of the two-dimensional electron gas in LaAlO3/SrTiO3(111) heterostructures.

Half-metallic materials have gained a lot of attention because of their unique properties and applications in spintronic devices. Despite the fact that these materials have been studied by several research groups there are very limited studies on their heterostructure (HS) systems. In the current study we have investigated the electronic and magnetic properties of (LaAlO3)6.5/(SrTiO3)2.5(111) HS using density functional theory (DFT) calculations. We demonstrate that the system exhibits a 100% spin-polarized two-dimensional electron gas (2DEG) which is extremely confined to the Ti 3d orbitals of the SrTiO3 layers. In particular, this system can keep its half-metallic properties under different in-plane strains from -3 to 2%. This property proves that this material has relatively stable half-metallic properties. In addition, the conducting and magnetic ground states of the system can also be tailored by changing in-plane strain and interfacial cation intermixing of La and Sr (Sr ⇔ La intermixing). By increasing the in-plane lattice parameters, this system has the ability to evolve from a nonmagnetic to a ferromagnetic metal and then to a half-metal and by further increasing the in-plane lattice parameter it becomes a ferromagnetic insulator. Sr ⇔ La intermixing can destroy the original half-metallic properties and the system exhibits an AFM Mott-type insulator phase. Our results demonstrate that the system has high potential for application in the field of spintronics, and opens the prospect of using LaAlO3/SrTiO3(111) HSs to explore quantum phase transitions.

Plasma big endothelin-1 predicts new-onset atrial fibrillation after surgical septal myectomy in patients with hypertrophic cardiomyopathy.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication in patients with obstructive hypertrophic cardiomyopathy (HOCM) who undergo surgical myectomy. POAF is associated with poor outcome. The role of plasma big endothelin-1 level in predicting atrial fibrillation after surgical septal myectomy in HOCM patients has not well been studied. METHODS: A total of 118 patients with HOCM who underwent surgical septal myectomy were recruited in this study. Plasma big endothelin-1 level was measured. The heart rhythm was continuously monitored during hospital stay. Preoperative, intraoperative, and postoperative variables were collected. RESULTS: POAF developed among 26 of the 118 patients (22%) in this study. Compared with those without POAF, patients with POAF were significantly older (53.5 ± 10.6 vs. 47.3 ± 13.6 years, P = 0.033), more likely to undergo mitral valve surgery (38.5% vs. 18.5%, P = 0.032), and had higher plasma big endothelin-1 levels (0.41 ± 0.19 vs. 0.27 ± 0.14 pmol/l, P = 0.001), longer hospital stay (9.1 ± 3.7 vs. 7.5 ± 2.8 days, P = 0.022), larger preoperative left atria (48.0 ± 5.2 vs. 44.1 ± 5.9 mm; P = 0.003). In the receiver operating characteristic curve analysis, the area under the curve for big endothelin-1 was 0.734 (95% CI, 0.634 to 0.834, P<0.001). In multivariate logistic regression analysis, preoperative big endothelin-1 level (OR 100.7, 95%CI: 5.0-2020.0, P = 0.003) and left atrial diameter (OR 1.106, 95%CI: 1.015-1.205, P = 0.022) were independent predictors of POAF. CONCLUSION: Elevated preoperative plasma big endothelin-1 level is an independent predictor of POAF in HOCM patients undergoing surgical septal myectomy.

Preoperative NT-proBNP Predicts Midterm Outcome After Septal Myectomy.

Background The prognostic value of N-terminal pro-brain natriuretic peptide ( NT -pro BNP ) in patients with hypertrophic cardiomyopathy who underwent septal myectomy has not been well studied. Methods and Results We retrospectively evaluated NT -pro BNP levels in 758 patients (46.1±13.8 years; median follow-up, 936 days) who underwent septal myectomy in our center between March 2011 and April 2018. The median NT -pro BNP level was 1450.5 (interquartile range 682.6-2649.5) pg/mL. Overall, 22 (2.9%) patients died during follow-up; of these, 86.4% were cardiovascular deaths. The 3-year survival free from all-cause mortality by tertile was 95.2% (95% CI 91.1% to 97.4%; NT -pro BNP >2080 pg/mL), 98.3% (95% CI 94.6% to 99.5%; NT -pro BNP , 947-2080 pg/mL), and 99.2% (95% CI , 94.4% to 99.9%; NT -pro BNP <947 pg/mL). The 3-year survival rate free from cardiovascular mortality by tertiles was 95.2% in the highest tertile, 98.8% in the middle tertile, and 99.2% in the lowest tertile. Cox regression analysis indicated that Ln( NT -pro BNP ) was a significantly independent predictor of all-cause mortality (hazard ratio 2.380, 95% CI 1.356-4.178, P=0.003) and cardiovascular mortality (hazard ratio 2.788, 95% CI 1.450-5.362, P=0.002). In addition, concomitant coronary artery bypass grafting for coronary artery disease was also an independent predictor of cardiovascular mortality (hazard ratio 5.178, 95% CI 1.597-16.789, P=0.006). Conclusions Increased preoperative NT -pro BNP level is a strong predictor of midterm mortality in patients undergoing septal myectomy.

Comparison of Outcomes of Mitral Valve Repair for Leaflet Prolapse with Advanced versus Mild/Moderate Myxomatous Degeneration.

There is limited information on long-term outcomes of mitral valve repair for mitral regurgitation (MR) caused by different degrees of myxomatous degeneration. The aim of this study was to compare the surgical results of patients with advanced and mild/moderate myxomatous mitral valve degeneration (MVD). We identified 130 patients (25 advanced and 105 mild/moderate MVD patients) who underwent mitral valve repair for MR and were pathologically diagnosed as myxomatous degeneration. Follow-up was 100% complete (mean length, 5.1 ± 1.8 years). Survival differed significantly between the advanced and mild/moderate MVD groups (76.0 ± 9.7% versus 95.0 ± 5.4% at 8 years, P < 0.001). The univariate predictors of mortality were advanced myxomatous degeneration, recurrent MR, and early series (surgeries before 2011). The mild/moderate MVD group had higher freedom from a moderate or severe MR rate compared with the advanced MVD group (77.4 ± 4.5% versus 50.5 ± 10.2% at 7 years, P = 0.003). Multivariable Cox analysis revealed advanced myxomatous degeneration and residual MR as independent predictors of recurrent moderate or severe MR. A total of 25 patients (19.2%) had persistent atrial fibrillation (AF) after repair. In multivariate analysis, advanced myxomatous degeneration was found to be an independent predictor of postoperative persistent AF.In conclusion, the long-term outcomes of mitral valve repair in patients with advanced MVD are poorer than in those with mild/moderate MVD. Advanced myxomatous degeneration is an independent predictor of recurrent moderate or severe MR and postoperative persistent AF in MVD patients performing repair, which deserves more attention before and after surgery.

Prognostic Significance and Risk of Atrial Fibrillation of Wolff-Parkinson-White Syndrome in Patients With Hypertrophic Cardiomyopathy.

To assess the mid-term mortality and risk of atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HC) and Wolff-Parkinson-White (WPW) syndrome, 40 patients with HC and WPW were enrolled in our center between 2010 and 2017. An age- and gender-matched comparison cohort of patients with HC without WPW (n = 160) was generated from the same center. The clinical profile and outcomes were assessed. Of 40 patients with WPW, 28 underwent accessory pathway (AP) elimination. Two patients (7%) had failed in AP elimination. During mid-term follow-up, 1 patient had an implantable cardioverter-defibrillator intervention. Fourteen patients had AF. A previous history of AF (hazard ratio [HR]: 4.69; 95% confidence interval [CI] 1.51 to 14.63) and left atrial dimension (HR: 1.12; 95% CI 1.03 to 1.23) at baseline were risk factors for AF occurrence during follow-up. The AP elimination significantly reduced risk for the incidence of AF (HR: 0.22; 95% CI 0.06 to 0.83). Compared with the control group, the prevalence of syncope and AF were significantly higher in the WPW group. During follow-up, no difference was identified in outcome measures consisting of all-cause death, cardiac transplantation, and implantable cardioverter-defibrillator intervention. A previous history of AF (HR: 5.20; 95% CI 2.63 to 10.30, p <0.001) and persistent existing WPW (HR: 3.64; 95% CI 1.63 to 8.11, p = 0.002) were independent risk factors for AF occurrence during follow-up in the entire cohort. In conclusion, although WPW was uncommon and might not be correlated with mid-term mortality in HC patients, WPW might increase the risk of AF occurrence. Additionally, AP elimination may reduce the risk of AF occurrence.

Comprehensive analysis of competitive endogenous RNAs network associated with head and neck squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) can regulate gene expression directly or indirectly through interacting with microRNAs (miRNAs). However, the role of differentially expressed mRNAs, lncRNAs and miRNAs, and especially their related competitive endogenous RNAs (ceRNA) network in head and neck squamous cell carcinoma (HNSCC), is not fully comprehended. In this paper, the lncRNA, miRNA, and mRNA expression profiles of 546 HNSCC patients, including 502 tumor and 44 adjacent non-tumor tissues, from The Cancer Genome Atlas (TCGA) were analyzed. 82 miRNAs, 1197 mRNAs and 1041 lncRNAs were found to be differentially expressed in HNSCC samples (fold change ≥ 2; P < 0.01). Further bioinformatics analysis was performed to construct a lncRNA-miRNA-mRNA ceRNA network of HNSCC, which includes 8 miRNAs, 71 lncRNAs and 16 mRNAs. Through survival analysis based on the expression profiles of RNAs in the ceRNA network, we detected 1 mRNA, 1 miRNA and 13 lncRNA to have a significant impact on the overall survival of HNSCC patients (P < 0.05). Finally, some lncRNAs, which are more important for survival, were also predicted. Our research provides data to further understand the molecular mechanisms implicated in HNSCC.

Hepatitis C virus and its protein NS4B activate the cancer-related STAT3 pathway via the endoplasmic reticulum overload response.

Oxidative stress induces the activation of signal transducer and activator of transcription 3 (STAT3), which plays an important role in hepatocellular carcinoma (HCC). We have previously reported that hepatitis C virus (HCV) and its protein NS4B induce the production of reactive oxygen species (ROS) via the endoplasmic reticulum overload response (EOR) in human hepatocytes. Here, we found that NS4B and HCV induce STAT3 activation and stimulate the expression of cancer-related STAT3 target genes, including VEGF, c-myc, MMP-9 and Mcl-1, by EOR in human hepatocytes. Moreover, the cancer-related STAT3 pathway activated by NS4B and HCV via EOR were found to promote human hepatocyte viability. Taken together, these findings revealed that HCV NS4B might contribute to HCC by activating the EOR-mediated cancer-related STAT3 pathway, and this could provide novel insights into HCV-induced HCC.

Oleanolic acid and ursolic acid: novel hepatitis C virus antivirals that inhibit NS5B activity.

Hepatitis C virus (HCV) infects up to 170 million people worldwide and causes significant morbidity and mortality. Unfortunately, current therapy is only curative in approximately 50% of HCV patients and has adverse side effects, which warrants the need to develop novel and effective antivirals against HCV. We have previously reported that the Chinese herb Fructus Ligustri Lucidi (FLL) directly inhibited HCV NS5B RNA-dependent RNA polymerase (RdRp) activity (Kong et al., 2007). In this study, we found that the FLL aqueous extract strongly suppressed HCV replication. Further high-performance liquid chromatography (HPLC) analysis combined with inhibitory assays indicates that oleanolic acid and ursolic acid are two antiviral components within FLL aqueous extract that significantly suppressed the replication of HCV genotype 1b replicon and HCV genotype 2a JFH1 virus. Moreover, oleanolic acid and ursolic acid exhibited anti-HCV activity at least partly through suppressing HCV NS5B RdRp activity as noncompetitive inhibitors. Therefore, our results for the first time demonstrated that natural products oleanolic acid and ursolic acid could be used as potential HCV antivirals that can be applied to clinic trials either as monotherapy or in combination with other HCV antivirals.

A critical role of perinuclear filamentous actin in spatial repositioning and mutually exclusive expression of virulence genes in malaria parasites.

Many microbial pathogens, including the malaria parasite Plasmodium falciparum, vary surface protein expression to evade host immune responses. P. falciparium antigenic variation is linked to var gene family-encoded clonally variant surface protein expression. Mututally exclusive var gene expression is partially controlled by spatial positioning; silent genes are retained at distinct perinuclear sites and relocated to transcriptionally active locations for monoallelic expression. We show that var introns can control this process and that var intron addition relocalizes episomes from a random to a perinuclear position. This var intron-regulated nuclear tethering and repositioning is linked to an 18 bp nuclear protein-binding element that recruits an actin protein complex. Pharmacologically induced F-actin formation, which is restricted to the nuclear periphery, repositions intron-carrying episomes and var genes and disrupts mutually exclusive var gene expression. Thus, actin polymerization relocates var genes from a repressive to an active perinuclear compartment, which is crucial for P. falciparium phenotypic variation and pathogenesis.

[Var gene family and antigen variation in Plasmodium falciparum].

An immunovariant adhesion protein family in Plasmodium falciparum named erythrocyte membrane protein 1 (PfEMP1), encoded by var genes, is responsible for both antigenic variation and cytoadhesion of infected erythrocytes at microvasculature sites throughout the body. The article summarizes antigen variation and pathogenicity, variation molecules expressed on infected erythrocytes, structure of var gene family, PfEMP1 adhesion properties, and regulation of variation in Plasmodium falciparum var gene family.

The membrane protein of SARS-CoV suppresses NF-kappaB activation.

Severe acute respiratory syndrome coronavirus (SARS-CoV) infects many organs, such as lung, liver, and immune organs and causes life-threatening atypical pneumonia, SARS causes high morbidity and mortality rates. The molecular mechanism of SARS pathogenesis remains elusive. Inflammatory stimuli can activate IkappaB kinase (IKK) signalsome and subsequently the nuclear factor kappa B (NF-kappaB), which influences gene expression of cyclooxygenase-2 (Cox-2) along with other transcription factors. In this work, we found that the membrane (M) protein of SARS-CoV physically interacted with IKKbeta using a co-immunoprecipitation assay (IPA). Expression of M suppressed tumor necrosis factor alpha (TNF-alpha) induced NF-kappaB activation using a luciferase reporter assay. Further investigation showed M protein suppressed Cox-2 expression using a luciferase reporter gene assay, RT-PCR and Western blot analysis. The carboxyl terminal of M protein was sufficient for the M protein function. Together, these results indicate that SARS-CoV M suppresses NF-kappaB activity probably through a direct interaction with IKKbeta, resulting in lower Cox-2 expression. Suppression of NF-kappaB activity and Cox-2 expression may contribute to SARS pathogenesis.

Torque teno virus (SANBAN isolate) ORF2 protein suppresses NF-kappaB pathways via interaction with IkappaB kinases.

Since the first discovery of Torque teno virus (TTV) in 1997, many researchers focused on its epidemiology and transcriptional regulation, but the function of TTV-encoded proteins remained unknown. The function of the TTV open reading frame (ORF) in the nuclear factor kappaB (NF-kappaB) pathway has not yet been established. In this study, we found for the first time that the TTV ORF2 protein could suppress NF-kappaB activity in a dose-dependent manner in the canonical NF-kappaB pathway. By Western blot analysis, we proved that the TTV ORF2 protein did not alter the level of NF-kappaB expression but prevented the p50 and p65 subunits from entering the nucleus due to the inhibition of IkappaBalpha protein degradation. Further immunoprecipitation assays showed that the TTV ORF2 protein could physically interact with IKKbeta as well as IKKalpha, but not IKKgamma. Luciferase assays and Western blot experiments showed that the TTV ORF2 protein could also suppress NF-kappaB activity in the noncanonical NF-kappaB pathway and block the activation and translocation of p52. Finally, we found that the TTV ORF2 protein inhibited the transcription of NF-kappaB-mediated downstream genes (interleukin 6 [IL-6], IL-8, and COX-2) through down-regulation of NF-kappaB. Together, these data indicate that the TTV ORF2 protein suppresses the canonical and noncanonical NF-kappaB pathways, suggesting that the TTV ORF2 protein may be involved in regulating the innate and adaptive immunity of organisms, contributing to TTV pathogenesis, and even be related to some diseases.

Up-regulation of IL-6 and TNF-alpha induced by SARS-coronavirus spike protein in murine macrophages via NF-kappaB pathway.

The clinical picture of severe acute respiratory syndrome (SARS) is characterized by an over-exuberant immune response with lung lymphomononuclear cells infilteration and proliferation that may account for tissue damage more than the direct effect of viral replication. To understand how cells response in the early stage of virus-host cell interaction, in this study, a purified recombinant S protein was studied for stimulating murine macrophages (RAW264.7) to produce proinflammatory cytokines (IL-6 and TNF-alpha) and chemokine IL-8. We found that direct induction of IL-6 and TNF-alpha release in the supernatant in a dose-, time-dependent manner and highly spike protein-specific, but no induction of IL-8 was detected. Further experiments showed that IL-6 and TNF-alpha production were dependent on NF-kappaB, which was activated through I-kappaBalpha degradation. These results suggest that SARS-CoV spike protein may play an important role in the pathogenesis of SARS, especially in inflammation and high fever.

Inhibition of HCV RNA-dependent RNA polymerase activity by aqueous extract from Fructus Ligustri Lucidi.

The development of effective antiviral drugs against hepatitis C virus (HCV) continues to be needed, since neither vaccines nor broadly effective therapeutic agents are available. HCV RNA-dependent RNA polymerase (NS5B) is strictly required for viral replication and thus represents an attractive target. Here, aqueous extracts from five traditional Chinese medicines were tested for their ability to inhibit NS5B activity by reporter assays using cell-based NS5B activity detecting systems. Among them, aqueous extract from Fructus Ligustri Lucidi exhibited a promising result, dose-dependent inhibition of the luciferase activity, an indicator of intracellular NS5B activity (p<0.001), in the absence of cytotoxicity. Further Quantitative RT-PCR assays and Western blot analysis showed aqueous extract from Fructus Ligustri Lucidi inhibited intracellular NS5B-catalyzed RNA synthesis dose-dependently (p<0.001) without affecting intracellular NS5B expression. Subsequent in vitro NS5B assays revealed that this extract could directly inhibit NS5B activity. Taken together, these results indicated that Fructus Ligustri Lucidi might offer a promising source of antiviral drugs against HCV NS5B. Purification of the active compound(s) and antiviral effect are clearly required in the future.

Hepatitis B virus X protein (HBx) activates ATF6 and IRE1-XBP1 pathways of unfolded protein response.

Numerous viruses including hepatitis B virus (HBV) induce endoplasmic reticulum (ER) stress, which interrupts protein folding causing accumulation of unfolded or misfolded proteins in ER. To alleviate the stress placed on ER, these proteins must be refolded or degraded by activating a specific cellular response known as ER stress response or unfolded protein response (UPR). Two UPR-specific signaling pathways involving transmembrane proteins ATF6 and XBP1 generate critical transcription factors that activate UPR-responsive genes. In this study, the role of the multifunctional regulatory protein of HBV (HBx protein) in activation of UPR was investigated. In Hep3B cells with transit or stable expression of HBx, XBP1 expression and ATF6 cleavage was observed, suggesting that the ATF6 and IRE1-XBP1 pathways were activated. Furthermore, these two pathways were also activated in HepG2.2.15 cells that constitutively replicate the intact HBV genome, and blocked at least partly by cotransfection with small interfering RNA (siRNA) expression plasmid that knocked down HBx expression. Our results clearly establish HBx as an inducer of UPR and the activator of the ATF6 and IRE1-XBP1 pathways of UPR. HBx-mediated activation of these pathways of UPR probably promote HBV replication and expression in liver cells, and contribute to liver pathogenesis, perhaps even to hepatocellular carcinoma (HCC) development.