The force-dependent filamin A-G3BP1 interaction regulates phase-separated stress granule formation.

Filamin A (FLNA) is an actin crosslinking protein that mediates mechanotransduction. External and internal mechanical forces, through the actin cytoskeleton, can induce conformational changes of the FLNA molecule to expose cryptic binding sites for its binding partners. Here, we identified Ras GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) as a new FLNA mechanobinding partner. Unlike other FLNA binding partners to the mechanosensing domain repeat 21 (R21), G3BP1 requires an additional neighboring repeat R22 to interact. We demonstrated that their interaction occurs in the cytosol of living cells in an actin polymerization-dependent manner. We also mapped the FLNA-binding site on G3BP1 and found that a F360A point mutation in the RNA recognition motif disrupts the interaction. RNA interfered with the FLNA-G3BP1 interaction, and FLNA did not localize in RNA-rich stress granules (SGs). Disruption of the interaction was sufficient to promote phase-separated SG formation, and arsenite treatment further stimulated the formation of SGs. Taken together, these data identify G3BP1 as a new mechanobinding protein that interacts with the FLNA mechanosensing domain R21 and suggest that SG formation is partially regulated by mechanical force.

SARS-CoV-2 Nsp8 suppresses MDA5 antiviral immune responses by impairing TRIM4-mediated K63-linked polyubiquitination.

Melanoma differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates antiviral innate immune responses to infection by RNA viruses. Upon recognition of viral dsRNA, MDA5 is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS and activation of TBK1 and IKKα/ß, subsequently leading to IRF3 and NF-κB phosphorylation. However, the specific E3 ubiquitin ligase for MDA5 K63-polyubiquitination has not been well characterized. Great numbers of symptomatic and severe infections of SARS-CoV-2 are spreading worldwide, and the poor efficacy of treatment with type I interferon and antiviral immune agents indicates that SARS-CoV-2 escapes from antiviral immune responses via several unknown mechanisms. Here, we report that SARS-CoV-2 nonstructural protein 8 (nsp8) acts as a suppressor of antiviral innate immune and inflammatory responses to promote infection of SARS-CoV-2. It downregulates the expression of type I interferon, IFN-stimulated genes and proinflammatory cytokines by binding to MDA5 and TRIM4 and impairing TRIM4-mediated MDA5 K63-linked polyubiquitination. Our findings reveal that nsp8 mediates innate immune evasion during SARS-CoV-2 infection and may serve as a potential target for future therapeutics for SARS-CoV-2 infectious diseases.

Additive-free Absorbable Keratin Sponge With Procoagulant Activity for Noncompressible Hemostasis.

The development of a natural, additive-free, absorbable sponge with procoagulant activity for noncompressible hemostasis remains a challenging task. In this study, we extracted high molecular weight keratin (HK) from human hair and transformed it into a hemostatic sponge with a well-interconnected pore structure using a foaming technique, freeze-drying, and oxidation cross-linking. By controlling the cross-linking degree, the resulting sponge demonstrated excellent liquid absorption ability, shape recovery characteristics, and robust mechanical properties. The HK10 sponge exhibited rapid liquid absorption, expanding up to 600% within 5 s. Moreover, the HK sponge showed superior platelet activation and blood cell adhesion capabilities. In SD rat liver defect models, the sponges demonstrated excellent hemostatic performance by sealing the wound and expediting coagulation, reducing the hemostatic time from 825 to 297 s. Furthermore, HK sponges have excellent biosafety, positioning them as a promising absorbable sponge with the potential for the treatment of noncompressible hemostasis.

Sleep Staging Framework with Physiologically Harmonized Sub-Networks.

Sleep screening is an important tool for both healthcare and neuroscientific research. Automatic sleep scoring is an alternative to the time-consuming gold-standard manual scoring procedure. Recently there have seen promising results on automatic stage scoring by extracting spatio-temporal features via deep neural networks from electroencephalogram (EEG). However, such methods fail to consistently yield good performance due to a missing piece in data representation: the medical criterion of the sleep scoring task on top of EEG features. We argue that capturing stage-specific features that satisfy the criterion of sleep medicine is non-trivial for automatic sleep scoring. This paper considers two criteria: Transient stage marker and Overall profile of EEG features, then we propose a physiologically meaningful framework for sleep stage scoring via mixed deep neural networks. The framework consists of two sub-networks: feature extraction networks, constructed in consideration of the physiological characteristics of sleep, and an attention-based scoring decision network. Moreover, we quantize the framework for potential use under an IoT setting. For proof-of-concept, the performance of the proposed framework is demonstrated by introducing multiple sleep datasets with the largest comprising 42,560 h recorded from 5,793 subjects. From the experiment results, the proposed method achieves a competitive stage scoring performance, especially for Wake, N2, and N3, with higher F1 scores of 0.92, 0.86, and 0.88, respectively. Moreover, the feasibility analysis of framework quantization provides a potential for future implementation in the edge computing field and clinical settings.

First Report of Meloidogyne enterolobii Infecting Yellow pitaya (Selenicereus megalanthus) in China.

Yellow pitaya, Selenicereus megalanthus, is a night-blooming, climbing cacti of tropical origin, which has received increasing attention for its potential as a new exotic fruit crop (Lichtenzveig et al. 2000). The crop is grown extensively in Hainan Province, China (3000 ha). In October 2021, a survey was conducted on a farm located in Changjiang (19°21'4″N, 108°47'2″S), Hainan Province, China. Some yellow pitaya plants were found that were stunted and chlorotic, with abnormally thin stems (Fig. 1B), and no symptoms on healthy plants (Fig. 1A). Dead plants were also observed. Many galls and females with egg masses were observed on roots (Figs. 1C & 1D). This is typical of root-knot nematode (RKN) infections, and the incidence of infection was 36.7%. Meloidogyne sp. females and egg masses were dissected from roots of the infected plants. The perineal pattern of females (n= 5) was round to oval-shaped with a high dorsal arch (Figs. 1I & 1J). Second-stage juveniles (J2s) had truncated lips (Figs. 1E & 1F) and long-conical tails with bluntly rounded tips (Figs. 1G & 1H). The J2s body length (n= 24) averaged 416.79 µm (349.21 to 472.76 µm) with a mean width of 15.36 µm (12.47 to 17.52 µm); mean stylet length was 11.16 µm (10.10 to 13.23 µm); tail length averaged 53.73 µm (43.46 to 65.90 µm). The morphological characteristics matched the original description of M. enterolobii (Yang and Eisenback 1983). Males were not found. Genomic DNA was extracted from eight single J2s, and the mitochondrial (mtDNA) region between COII and 16S rRNA gene was amplified with primers C2F3/1108 (Powers and Harris 1993). A 652-bp DNA fragment was obtained, for which the sequence (GenBank accession no. OP122499) was 100% identical to the sequences of M. enterolobii isolates from China（MN269947）and the USA (MN809527). Furthermore, species identification was also confirmed using M. enterolobii specific primers Me-F/Me-R. An amplicon size of ∼230 bp was obtained, which is consistent with those previously reported for M. enterolobii (Fig. 2) (Long et al. 2006). Therefore, this population was identified as M. enterolobii based on morphological and molecular characteristics. Pathogenicity tests were performed in the greenhouse at 26℃ and 80% relative humidity with a 14-h/10-h light/dark photoperiod. Ten RKN-free S. megalanthus seedlings were transplanted into pots containing sterilized soil. After 3 weeks, the roots of 5 plants were inoculated with 3,000 eggs and J2s of M. enterolobii per plant. Five uninoculated plants were used as control plants. After 2 months, no galling or symptoms were observed on the control plants. All inoculated plants had galled roots similar to those observed in the field. Females and egg masses were obtained by dissecting galls. The nematode reproduction factor (RF= final population/initial population) was 1.9. Adult females (n= 5) dissected from inoculated plants were identified as M. enterolobii with sequence-specific primers Me-F/Me-R, thus confirming pathogenicity. The pathogenicity test was carried out twice with similar results. M. enterolobii is one of the most damaging species of RKN, due to its wide host range, high level of pathogenicity, and ability to develop and reproduce on several crops with resistance genes to other RKN (Castagnone-Sereno 2012). To our knowledge, this is the first report of S. megalanthus (yellow pitaya) as a host of M. enterolobii in China. Further studies are needed to develop and evaluate integrated management strategies.

Multifunctional Metasurface Tuning by Liquid Crystals in Three Dimensions.

Optical metasurfaces present remarkable opportunities for manipulating wave propagation in unconventional ways, surpassing the capabilities of traditional optical devices. In this work, we introduce and demonstrate a multifunctional dynamic tuning of dielectric metasurfaces containing liquid crystals (LCs) through an effective three-dimensional (3D) control of the molecular orientation. We theoretically and experimentally study the spectral tuning of the electric and magnetic resonances of dielectric metasurfaces, which was enabled by rotating an external magnetic field in 3D. Our approach allows for the independent control of the electric and magnetic resonances of a metasurface, enabling multifunctional operation. The magnetic field tuning approach eliminates the need for the pre-alignment of LCs and is not limited by a finite set of directions in which the LC molecules can be oriented. Our results open new pathways for realizing dynamically reconfigurable metadevices and observing novel physical effects without the usual limitations imposed by the boundary conditions of LC cells and the external voltage.

The Piezocatalytic Degradation of Sulfadiazine by Lanthanum-Doped Barium Titanate.

Piezocatalysis, a heterogeneous catalytic technique, leverages the periodic electric field changes generated by piezoelectric materials under external forces to drive carriers for the advanced oxidation of organic pollutants. Antibiotics, as emerging trace organic pollutants in water sources, pose a potential threat to animals and drinking water safety. Thus, piezoelectric catalysis can be used to degrade trace organic pollutants in water. In this work, BaTiO3 and La-doped BaTiO3 were synthesized using an improved sol-gel-hydrothermal method and used as piezocatalytic materials to degrade sulfadiazine (SDZ) with ultrasound activation. High-crystallinity products with nano cubic and spherical morphologies were successfully synthesized. An initial concentration of SDZ ranging from 1 to 10 mg/L, a catalysis dosage range from 1 to 2.5 mg/mL, pH, and the background ions in the water were considered as influencing factors and tested. The reaction rate constant was 0.0378 min-1 under the optimum working conditions, and the degradation efficiency achieved was 89.06% in 60 min. La-doped BaTiO3 had a better degradation efficiency, at 14.98% on average, compared to undoped BaTiO3. Further investigations into scavengers revealed a partially piezocatalytic process for the degradation of SDZ. In summary, our work provides an idea for green environmental protection in dealing with new types of environmental pollution.

Latent profile analysis of empathy ability and its relationship with professional quality of life among hospice nurses in China.

BACKGROUND: Empathy is important in hospice nursing clinics and may influence nurses' professional quality of life (ProQOL). However, present studies ignoring each empathic dimension, and few researches have explored the correlation between empathy and ProQOL in hospice nurses in Asia. To better understand hospice nurses' empathy abilities in China and its relationship with ProQOL, the aim of this study was to identify the latent profiles and its influencing factors of hospice nurses' empathy ability, as well as differences in ProQOL across each latent profile. METHODS: A cross-sectional study was conducted from October 2021 to September 2022, and a total of 725 hospice nurses were recruited from different geographic regions in China. Participants completed the Empathy Ability Scale for Hospice Nurses and the Brief Professional Quality of Life Scale. Latent profile analysis (LPA) was employed to identify latent profiles of empathy ability among hospice nurses in China. The predictors of hospice nurses' empathy ability in different latent profiles were assessed using multinomial logistic regression analysis. One-way ANOVA test and the Kruskal-Wallis test were used to compare the ProQOL scores in each latent profile of nurses' empathy ability. RESULTS: This study identified three latent profiles of hospice nurses' empathy ability, and those profiles labelled "poor empathy ability-high surface empathy expression" (n = 216, 29.8%), "moderate empathy ability" (n = 359, 49.5%) and "high empathy ability-high deep empathy expression" (n = 150, 20.7%). Multinomial logistic regression analysis suggested that age, hospital level, whether income meets expectations, interests in hospice care work, hospice work experience, and receiving psychological counselling were predictors of hospice nurses' profile membership of empathy ability. The scores of compassion satisfaction (CS) and burnout (BO) in ProQOL were significantly different across each profile (P < 0.001), while scores of secondary traumatic stress (STS) in ProQOL were not different across each profile (P = 0.294). CONCLUSIONS: Hospice nurses' empathy ability was divided into three latent profiles, and enhancing empathy ability may be conducive to improving hospice nurses' CS, while reducing BO, thus fostering their overall quality of life. Nursing managers should identify hospice nurses at higher risk of BO and implement targeted interventions focused on enhancing nurse's empathy abilities.

Identification of Filamin A Mechanobinding Partner III: SAV1 Specifically Interacts with Filamin A Mechanosensitive Domain 21.

Filamin A (FLNA) cross-links actin filaments and mediates mechanotransduction by force-induced conformational changes of its domains. FLNA's mechanosensitive immunoglobulin-like repeats (R) interact with each other to create cryptic binding sites, which can be exposed by physiologically relevant mechanical forces. Using the FLNA mechanosensing domains as an affinity ligand followed by stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics, we recently identified smoothelin and fimbacin as FLNA mechanobinding proteins. Here, using the mechanosensing domain as an affinity ligand and two labeled amino acids, we identify salvador homologue 1 (SAV1), a component of the Hippo pathway kinase cascade, as a new FLNA mechanobinding partner. We demonstrate that SAV1 specifically interacts with the cryptic C-D cleft of FLNA R21 and map the FLNA-binding site on SAV1. We show that point mutations on the R21 C strand block the SAV1 interaction and find that SAV1 contains a FLNA-binding motif in the central region (116Phe-124Val). Point mutations F116A and T118A (FT/AA) disrupt the interaction. A proximity ligation assay reveals that their interaction occurs in the cytosol in an actin polymerization-dependent manner. Although SAV1 is typically found in the cytosol, disrupting the interaction between SAV1 and FLNA causes SAV1 to diffuse to the nucleus and YAP1 to diffuse to the cytosol in an inverse relationship. These results suggest that FLNA mediates regulation of the Hippo pathway through actin polymerization-dependent interaction with SAV1.

Serpina3c deficiency induced necroptosis promotes non-alcoholic fatty liver disease through ß-catenin/Foxo1/TLR4 signaling.

Non-alcoholic fatty liver disease (NAFLD) is a public health challenge and an increasing cause of chronic liver disease worldwide. However, the underlying molecular mechanism remains unclear. The aim of this study was to determine the precise role of serpina3c in the process of NAFLD. Male Apoe-/- /serpina3c-/- double knockout (DKO) and Apoe-/- mice were fed a high-fat diet (HFD) for 12 weeks. Several markers of steatosis and inflammation were evaluated. In vitro cell models induced by palmitic acid (PA) treatment were used to evaluate the beneficial effect of serpina3c on necroptosis and the underlying molecular mechanism. Compared with Apoe-/- mice, DKO mice exhibited a significantly exacerbated hepatic steatosis, increased hepatic triglyceride content and expression of genes involved in lipid metabolism (SREBP1c and SCD1), promoted hepatic inflammation and fibrosis, promoted necroptosis by increasing expression of receptor-interacting protein 3 (RIP3), phosphorylated mixed lineage kinase domain-like (MLKL) and high mobility group box 1 (HMGB1). Notably, serpina3c deficiency increased ß-catenin, Foxo1, and Toll-like receptor 4 (TLR4) protein expression. In vitro , serpina3c knockdown promoted necroptosis and lipid droplet formation under condition of lipotoxicity. However, these phenomena were reversed by the overexpression of serpina3c. Mechanistically, downregulation of serpina3c expression promoted Foxo1 and ß-catenin colocalized in the nucleus under condition of lipotoxicity, consequently upregulating the expression of TLR4. Conversely, disruption of Foxo1-ß/catenin by Foxo1 and ß-catenin inhibitors decreased TLR4 expression and ameliorated hepatic necroptosis in vitro. This study highlights a novel mechanism that serpina3c modulates NAFLD development by inhibiting necroptosis via ß-catenin/Foxo1/TLR4.

BRLF1 suppresses RNA Pol III-mediated RIG-I inflammasome activation in the early EBV lytic lifecycle.

Latent infection with herpesviruses constitutively activates inflammasomes, while lytic replication suppresses their activation through distinct mechanisms. However, how Epstein-Barr virus (EBV) lytic replication inhibits the activation of inflammasomes remains unknown. Here, we reveal that the EBV immediate-early protein BRLF1 inhibits inflammasome activation, and BRLF1 deficiency significantly increases the activation of inflammasomes and pyroptosis during early lytic lifecycle. BRLF1 interacts with RNA polymerase III subunits to suppress immunostimulatory small RNA transcription, RIG-I inflammasome activation, and antiviral responses. Consequently, BRLF1-deficient EBV primary infection induces robust T-cell and NK cell activation and killing through IL-1ß and IL-18. A BRLF1-derived peptide that inhibits inflammasome activation is sufficient to suppress T-cell and NK cell responses during BRLF1-deficient EBV primary infection in lymphocytes. These results reveal a novel mechanism involved in the evasion of inflammasome activation and antiviral responses during EBV early lytic infection and provide a promising approach for the manipulation of inflammasomes against infection of oncogenic herpesviruses.

Anomalous Klein tunneling in two-dimensional black phosphorus heterojunctions.

We investigate the role of heterojunctions of few-layer black phosphorus (BP) with band gap inversion in governing the quantum transport behaviors. Numerical results show that in the armchair junction, electron tunneling probability occurs under approximately normal incidence with its magnitude T > 0.5. More interestingly, when different band gaps are taken into account on two sides of this junction, the maximum transmission appears away from the center of the valley, leading to the occurrence of anomalous Klein tunneling. Such a result tends to be independent of the width and height of the potential barrier. On the other hand, in the zigzag junction, electron transmission arises in a larger range of angles, and perfect electron transmission (T = 1.0) or reflection appears under specific band gap configurations. These findings provide a new understanding for the study of Klein tunneling and anomalous Klein tunneling based on tunable band gap BP or other two-dimensional Dirac semimetals.

Delivery of Mir-196c-3p with NIR-II light-triggered gel attenuates cardiomyocyte ferroptosis in cardiac ischemia-reperfusion injury.

Ferroptosis plays an important role in ischemia-reperfusion (I/R)-induced cardiac injury and there are many defects in current targeted delivery of miRNAs for the treatment of ferroptosis. We herein report a unique hydrogel (Gel) that can be triggered by a near-infrared-II (NIR-II) light with deep tissue penetration and biocompatible maximum permissible exposure (MPE) value for in situ treatment after I/R. The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Using 1064 nm light irradiation, local microenvironment photothermal-triggered on-demand noninvasive controllable delivery of miRNA was achieved, aiming to inhibit I/R-induced ferroptosis. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in I/R model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and LOX expression.

Cancer drug resistance related microRNAs: recent advances in detection methods.

Drug resistance is a significant factor that hinders the success of cancer chemotherapy. The widely recognized mechanisms of drug resistance include changes to cell proliferation, cycle/apoptosis, drug metabolism/transport, DNA damage and the epithelial to mesenchymal transition. MicroRNAs (miRNAs), short non-coding RNAs with lengths of approximately 19-25 nucleotides, are related to cancer drug resistance, which is regulated by the aforementioned mechanisms. Based on the importance of miRNAs in regulating drug resistance, it is also necessary to take appropriate miRNA detection methods into consideration. To date, a number of advanced miRNA detection methods with high specificity and sensitivity have been developed, such as isothermal amplification-based methods, nanomaterial-based methods, chromatography-based methods, mass spectrometry-based methods and so on. Herein, biogenesis of miRNAs, the relationship between miRNAs and cancer drug resistance, and miRNA detection methods are introduced and discussed to facilitate the development of non-invasive diagnosis and inhibition of cancer drug resistance.

A qualitative exploration of "empathic labor" in Chinese hospice nurses.

BACKGROUND: Hospice nurses may devote more emotional labor during the empathy process with patients, and this empathy can be used as a form of psychological behavior of emotional labor in the hospice care model. The aim of this study was to analyze hospice nurses' empathy characteristics in the context of emotional labor theory, and explore the impact of empathy on patient care. METHODS: We conducted semi-participant observations from three hospitals and multicenter in-depth interviews with n = 26 hospice nurses from eight cities. Interviews were transcribed, and directed content analysis was applied. RESULTS: Two categories with four sub-categories were extracted from the data analysis. Category 1 described the "empathic labor" process which covers cognitive empathy (including empathic imagination, empathic consideration, and empathic perception) and affective empathy (including natural empathy, surface empathy, and deep empathy). The second category concerns the outcome of nurses' "empathic labor" which incorporates both positive and negative effects. CONCLUSIONS: The findings indicated that hospice nurses' empathy process should be understood as emotional labor. Nursing managers should pay more attention to raising the ability of deep empathy with hospice nurses, and explore more sufficient active empowerment strategies to alleviate the negative impact of empathy on nurses and to strengthen nurses' deep empathy with terminal ill patients.

BRLF1-dependent viral and cellular transcriptomes and transcriptional regulation during EBV primary infection in B lymphoma cells.

The immediate-early protein BRLF1 plays important roles in lytic infection of Epstein-Barr virus (EBV), in which it activates lytic viral transcription and replication. However, knowledge of the influence of BRLF1 on cellular gene expression and transcriptional reprogramming during the early lytic cycle remains limited. In the present study, deep RNA-sequencing analysis identified all differentially expressed genes (DEGs) and alternative splicing in B lymphoma cells subjected to wild-type and BRLF1-deficient EBV primary infection. The BRLF1-dependent cellular DEGs were annotated, and major differentially enriched pathways were related to DNA replication and transcription, immune and inflammatory responses, cytokine-receptor interactions and chemokine signaling and metabolic processes. Furthermore, analysis of BRLF1-binding proteins by mass spectrometry shows that BRLF1 binds to and cooperates with several transcription factors and components of the spliceosome and then influences both RNA polymerase II-dependent transcription and pre-mRNA splicing. The RTA-binding RRE motifs or specific motifs of unique cooperative transcription factors in viral and cellular DEG promoter regions indicate that BRLF1 employs different strategies for regulating viral and cellular transcription. Thus, our study characterized BRLF1-dependent cellular and viral transcriptional profile during primary infection and then revealed the comprehensive virus-cell interaction and alterations of transcription during EBV primary infection and lytic replication.

The microRNA476a-RFL module regulates adventitious root formation through a mitochondria-dependent pathway in Populus.

For woody plants, clonal propagation efficiency is largely determined by adventitious root (AR) formation at the bases of stem cuttings. However, our understanding of the molecular mechanisms contributing to AR morphogenesis in trees remains limited, despite the importance of vegetative propagation, currently the most common practice for tree breeding and commercialization. Here, we identified Populus-specific miR476a as a regulator of wound-induced adventitious rooting that acts by orchestrating mitochondrial homeostasis. MiR476a exhibited inducible expression during AR formation and directly targeted several Restorer of Fertility like (RFL) genes encoding mitochondrion-localized pentatricopeptide repeat proteins. Genetic modification of miR476a-RFL expression revealed that miR476a/RFL-mediated dynamic regulation of mitochondrial homeostasis influences AR formation in poplar. Mitochondrial perturbation via exogenous application of a chemical inhibitor indicated that miR476a/RFL-directed AR formation depends on mitochondrial regulation that acts via auxin signaling. Our results thus establish a microRNA-directed mitochondrion-auxin signaling cascade required for AR development, providing insights into the role of mitochondrial regulation in the developmental plasticity of plants.

Reduced amino acid Schiff base containing ruthenium(III) complexes: Synthesis, characterization, DNA interaction, and in vitro cytotoxicity.

A number of reduced amino Schiff base ligands and corresponding ruthenium(III) complexes were designed and prepared based on the fact that amino acids not only possess multiple coordinate atoms but also improve the solubility of drugs in the body. The interaction of the complexes with calf thymus DNA was analyzed with spectroscopic methods of ultraviolet-visible absorption spectra, DNA competitive binding with ethidium bromide, circular dichroism spectra, and DNA melting experiments, and DNA viscosity measurements, indicating that the complexes bind to DNA primarily in the grooving mode. With respect to the ligands, the cytotoxicity in vitro of the complexes against Hela, A549, and MCF-7 cells was much enhanced, with most of the IC50 values less than 50 µM or even comparable with those of cisplatin.

The function of targeted host genes determines the oncogenicity of HBV integration in hepatocellular carcinoma.

BACKGROUND & AIMS: Although hepatitis B virus (HBV) integration into the human genome has been considered as one of the major causative factors to hepatocarcinogenesis, the underlying mechanism(s) was still elusive. Here we investigate the essential difference(s) of HBV integration between HCC tumor and adjacent non-tumor tissues and explore the factor(s) that determine the oncogenicity of HBV integration. METHODS: 1115 HBV integration sites were collected from four recent studies. Functional annotation analysis of integration targeted host genes (ITGs) was performed using DAVID based on Gene Ontology and KEGG pathway databases. Array-based expression profiles, real-time qPCR and western blot were used to detect the expression of recurrent integration targeted genes (RTGs). The biological consequences of the overexpression of UBXN8 in 8 HCC cell lines were studied in vitro. RESULTS: HBV is prone to integrate in genic regions (exons, introns, and promoters) and gene-dense regions. Functional annotation analysis reveals that, compared to those in adjacent non-tumor tissues, ITGs in HCC tumor tissues were significantly enriched in functional terms related to negative regulation of cell death, transcription regulation, development and differentiation, and cancer related pathways. 32% of the 75 RTGs identified in this analysis expressed abnormally in HCC tissues. UBXN8, one of the RTGs, was identified as a new tumor suppressor candidate which functions in a TP53 dependent manner. CONCLUSIONS: The oncogenicity of HBV integration was determined, to some extend by the function of HBV integration targeted host genes in HCC.