Evolutionary trajectory of TRPM2 channel activation by adenosine diphosphate ribose and calcium.

Ion channel activation upon ligand gating triggers a myriad of biological events and, therefore, evolution of ligand gating mechanism is of fundamental importance. TRPM2, a typical ancient ion channel, is activated by adenosine diphosphate ribose (ADPR) and calcium and its activation has evolved from a simple mode in invertebrates to a more complex one in vertebrates, but the evolutionary process is still unknown. Molecular evolutionary analysis of TRPM2s from more than 280 different animal species has revealed that, the C-terminal NUDT9-H domain has evolved from an enzyme to a ligand binding site for activation, while the N-terminal MHR domain maintains a conserved ligand binding site. Calcium gating pattern has also evolved, from one Ca2+-binding site as in sea anemones to three sites as in human. Importantly, we identified a new group represented by olTRPM2, which has a novel gating mode and fills the missing link of the channel gating evolution. We conclude that the TRPM2 ligand binding or activation mode evolved through at least three identifiable stages in the past billion years from simple to complicated and coordinated. Such findings benefit the evolutionary investigations of other channels and proteins.

Synthesis and Catalytic Performance of Mo2C/MoS2 Composite Heterojunction Catalysts.

Hydrogen, as a clean, safe, and efficient energy carrier, is one of the hot energy sources that have attracted much attention. Mo2C, due to the introduction of C atoms, makes the atomic spacing of the Mo lattice decrease and changes the width of the d-band, which makes the electronic properties of Mo2C similar to that of Pt noble metals, exhibiting excellent electrochemical hydrogen precipitation performance. MoS2, due to its special crystal structure and tunable electronic structure, has been widely studied. In this paper, Mo2C nanoparticles were prepared by high-temperature carbonization, and then two-dimensional layered MoS2 were be loaded on Mo2C nanoparticles by the hydrothermal method to synthesize Mo2C/MoS2 composite catalysts. Their electrochemical hydrogen precipitation (HER) performance under acidic conditions was tested. The above catalysts were also characterized by modern material testing methods such as XRD, SEM, TEM, and XPS. The results showed that the composite catalysts exhibited the most excellent electrochemical hydrogen precipitation performance at Mo2C/MoS2-3, with the lowest overpotential at a current density of 10 mA cm-2, Tafel slope, and electrochemical impedance. At the same time, the electrochemically active area was dramatically enhanced, with good stability under prolonged testing. The catalytic activity was significantly improved compared with that of Mo2C and MoS2. The characterization and experimental results indicate that the heterogeneous structure of Mo2C and MoS2 formed a built-in electric field between the two, which accelerated the electron transfer efficiency and provided more active sites. The Mo2C/MoS2 composite catalyst is a low-cost, easy-to-prepare, and high-efficiency electrochemical hydrogen precipitation catalyst, providing a new idea for developing green and clean energy.

Region-Aware Color Smudging.

Color smudge operations from digital painting software enable users to create natural shading effects in high-fidelity paintings by interactively mixing colors. To precisely control results in traditional painting software, users tend to organize flat-filled color regions in multiple layers and smudge them to generate different color gradients. However, the requirement to carefully deal with regions makes the smudging process time-consuming and laborious, especially for non-professional users. This motivates us to investigate how to infer user-desired smudging effects when users smudge over regions in a single layer. To investigate improving color smudge performance, we first conduct a formative study. Following the findings of this study, we design SmartSmudge, a novel smudge tool that offers users dynamical smudge brushes and real-time region selection for easily generating natural and efficient shading effects. We demonstrate the efficiency and effectiveness of the proposed tool via a user study and quantitative analysis.

The scaffold of neutrophil extracellular traps promotes CCA progression and modulates angiogenesis via ITGAV/NFκB.

Neutrophil extracellular traps (NETs) have garnered attention for their dual role in host defense and tumor promotion. With their involvement documented across a spectrum of tumors, their influence on the progression of cholangiocarcinoma (CCA) is of paramount interest. We employed immunohistochemistry and immunofluorescence to detect NET deposition in CCA tissues. Through in vitro and in vivo investigation, including CCA organoid and transposon-based models in PAD4 KO mice, we explored the effects of NETs on cell proliferation and metastasis. Molecular insights were gained through RNA sequencing, enzyme linked immunosorbent assay, and chromatin immunoprecipitation. Elevated intratumoral NET deposition within CCA tissues was associated with poor survival. The influence of NETs on CCA proliferation, migration and invasion was primarily mediated by NET-DNA. RNA sequencing unveiled the activation of the NFκB signaling pathway due to NET-DNA stimulation. NET-DNA pull-down assay coupled with mass spectrometry revealed the interaction between NET-DNA and αV integrin (ITGAV), culmination in the activation of the NFκB pathway. Furthermore, NET-DNA directly upregulated the expression of VEGF-A in cancer cells. The study unequivocally establishes NETs as facilitators of CCA progression, orchestrating proliferation, metastasis, and angiogenesis through ITGAV/NFκB pathway activation. This novel insight positions NETs as prospective therapeutic targets for managing CCA patients. By implementing a variety of methodologies and drawing intricate connections between NETs, DNA interactions, and signaling pathways, this research expands our comprehension of the complex interplay between the immune system and cancer progression, offering promising avenues for intervention.

TRPM2 as a conserved gatekeeper determines the vulnerability of DA neurons by mediating ROS sensing and calcium dyshomeostasis.

Different dopaminergic (DA) neuronal subgroups exhibit distinct vulnerability to stress, while the underlying mechanisms are elusive. Here we report that the transient receptor potential melastatin 2 (TRPM2) channel is preferentially expressed in vulnerable DA neuronal subgroups, which correlates positively with aging in Parkinson's Disease (PD) patients. Overexpression of human TRPM2 in the DA neurons of C. elegans resulted in selective death of ADE but not CEP neurons in aged worms. Mechanistically, TRPM2 activation mediates FZO-1/CED-9-dependent mitochondrial hyperfusion and mitochondrial permeability transition (MPT), leading to ADE death. In mice, TRPM2 knockout reduced vulnerable substantia nigra pars compacta (SNc) DA neuronal death induced by stress. Moreover, the TRPM2-mediated vulnerable DA neuronal death pathway is conserved from C. elegans to toxin-treated mice model and PD patient iPSC-derived DA neurons. The vulnerable SNc DA neuronal loss is the major symptom and cause of PD, and therefore the TRPM2-mediated pathway serves as a promising therapeutic target against PD.

Effects of Building Directions on Microstructure, Impurity Elements and Mechanical Properties of NiTi Alloys Fabricated by Laser Powder Bed Fusion.

For NiTi alloys prepared by the Laser Powder Bed Fusion (LPBF), changes in the building directions will directly change the preferred orientation and thus directly affect the smart properties, such as superelasticity, as well as change the distribution state of defects and impurity elements to affect the phase transformation behaviour, which in turn affects the smart properties at different temperatures. In this study, the relationship between impurity elements, the building directions, and functional properties; the effects of building directions on the crystallographic anisotropy; phase composition; superelastic properties; microhardness; geometrically necessary dislocation (GND) density; and impurity element content of NiTi SMAs fabricated by LPBF were systematically studied. Three building directions measured from the substrate, namely, 0°, 45° and 90°, were selected, and three sets of cylindrical samples were fabricated with the same process parameters. Along the building direction, a strong <100>//vertical direction (VD) texture was formed for all the samples. Because of the difference in transformation temperature, when tested at 15 °C, the sample with the 45° orientation possessed the highest strain recovery of 3.2%. When tested at the austenite phase transformation finish temperature (Af)+10 °C, the 90° sample had the highest strain recovery of 5.83% and a strain recovery rate of 83.3%. The sample with the 90° orientation presented the highest microhardness, which was attributed to its high dislocation density. Meanwhile, different building directions had an effect on the contents of O, C, and N impurity elements, which affected the transformation temperature by changing the Ni/Ti ratio. This study innovatively studied the impurity element content and GND densities of compressive samples with three building directions, providing theoretical guidance for LPBFed NiTi SMA structural parts.

Three-dimensional assessment of facial asymmetry in class III subjects, part 2: evaluating asymmetry index and asymmetry scores.

OBJECTIVES: To evaluate the outcomes of corrective surgical treatment for craniofacial asymmetry using four different methods with the aim of developing the best technique for craniofacial asymmetry assessment. MATERIALS AND METHODS: CBCT images of twenty-one class III subjects with surgically corrected craniofacial asymmetry and twenty-one matched controls were analyzed. Twenty-seven hard tissue landmarks were used to quantify asymmetry using the following methodologies: the asymmetry index (AI), asymmetry scores based on the clinically derived midline (CM), Procrustes analysis (PA), and modified Procrustes analysis (MPA). RESULTS: Modified Procrustes analysis successfully identified pre-operative asymmetry and revealed severe asymmetry at the mandibular regions compared to controls, which was comparable to the asymmetry index and clinically derived midline methods, while Procrustes analysis masked the asymmetric characteristics. Likewise, when comparing the post-surgical outcomes, modified Procrustes analysis not only efficiently determined the changes evidencing decrease in facial asymmetry but also revealed significant residual asymmetry in the mandible, which was congruent with the asymmetry index and clinically derived midline methods but contradictory to the results shown by Procrustes analysis. CONCLUSIONS: In terms of quantifying cranio-facial asymmetry, modified Procrustes analysis has evidenced to produce promising results that were comparable to the asymmetry index and the clinically derived midline, making it a more viable option for craniofacial asymmetry assessment. CLINICAL RELEVANCE: Modified Procrustes analysis is proficient in evaluating cranio-facial asymmetry with more valid clinical representation and has potential applications in assessing asymmetry in a wide spectrum of patients, including syndromic patients.

CreatureShop: Interactive 3D Character Modeling and Texturing From a Single Color Drawing.

Creating 3D shapes from 2D drawings is an important problem with applications in content creation for computer animation and virtual reality. We introduce a new sketch-based system, CreatureShop, that enables amateurs to create high-quality textured 3D character models from 2D drawings with ease and efficiency. CreatureShop takes an input bitmap drawing of a character (such as an animal or other creature), depicted from an arbitrary descriptive pose and viewpoint, and creates a 3D shape with plausible geometric details and textures from a small number of user annotations on the 2D drawing. Our key contributions are a novel oblique view modeling method, a set of systematic approaches for producing plausible textures on the invisible or occluded parts of the 3D character (as viewed from the direction of the input drawing), and a user-friendly interactive system. We validate our system and methods by creating numerous 3D characters from various drawings, and compare our results with related works to show the advantages of our method. We perform a user study to evaluate the usability of our system, which demonstrates that our system is a practical and efficient approach to create fully-textured 3D character models for novice users.

Nanomicelles for GLUT1-targeting hepatocellular carcinoma therapy based on NADPH depletion.

Hepatocellular carcinoma (HCC) is a malignant tumor leading cancer-associated high mortality worldwide. Unfortunately, the most commonly used drug therapeutics not only lack of target ability and efficiency, but also exhibit severe systemic toxicity to normal tissues. Thus, effective and targeted nanodrug of HCC therapy is emerging as a more important issue. Here, we design and develop the novel nanomicelles, namely Mannose-polyethylene glycol 600-Nitroimidazole (Man-NIT). This micelle compound with high purity comprise two parts, which can self-assemble into nanoscale micelle. The outer shell is selected mannose as hydrophilic moiety, while the inner core is nitroimidazole as hydrophobic moiety. In the cell experiment, Man-NIT was more cellular uptake by HCCLM3 cells due to the mannose modification. Mannose as a kind of glucose transporter 1 (GLUT1) substrate, can specifically recognize and bind to over-expressed GLUT1 on carcinoma cytomembrane. The nitroimidazole moiety of Man-NIT was reduced by the over-expressed nitroreductase with reduced nicotinamide adenine dinucleotide phosphate (NADPH) as the cofactor, resulting in transient deletion of NADPH and glutathione (GSH). The increase of reactive oxygen species (ROS) in HCCLM3 cells disturbed the balance of redox, and finally caused the death of tumor cells. Additional in vivo experiment was conducted using twenty-four male BALB/c nude mice to build the tumor model. The results showed that nanomicelles were accumulated in the liver of mice. The tumor size and pathological features were obviously improved after nanomicelles treatment. It indicates that namomicelles have a tumor inhibition effect, especially Man-NIT, which may be a potential nanodrug of chemotherapeutics for HCC therapy.

Targeting uridine-cytidine kinase 2 induced cell cycle arrest through dual mechanism and could improve the immune response of hepatocellular carcinoma.

BACKGROUND: Pyrimidine metabolism is critical for tumour progression. Uridine-cytidine kinase 2 (UCK2), a key regulator of pyrimidine metabolism, is elevated during hepatocellular carcinoma (HCC) development and exhibits carcinogenic effects. However, the key mechanism of UCK2 promoting HCC and the therapeutic value of UCK2 are still undefined. The aim of this study is to investigate the potential of UCK2 as a therapeutic target for HCC. METHODS: Gene expression matrices were obtained from public databases. RNA-seq, co-immunoprecipitation and RNA-binding protein immunoprecipitation were used to determine the mechanism of UCK2 promoting HCC. Immune cell infiltration level and immune-related functional scores were evaluated to assess the link between tumour microenvironment and UCK2. RESULTS: In HCC, the expression of UCK2 was upregulated in part by TGFß1 stimulation. UCK2 promoted cell cycle progression of HCC by preventing the degradation of mTOR protein and maintaining the stability of PDPK1 mRNA. We also identified UCK2 as a novel RNA-binding protein. Downregulation of UCK2 induced cell cycle arrest and activated the TNFα/NFκB signalling pathway-related senescence-associated secretory phenotype to modify the tumour microenvironment. Additionally, UCK2 was a biomarker of the immunosuppressive microenvironment. Downregulated UCK2 induced a secretory phenotype, which could improve the microenvironment, and decreased UCK2 remodelling metabolism could lower the resistance of tumour cells to T-cell-mediated killing. CONCLUSIONS: Targeting UCK2 inhibits HCC progression and could improve the response to immunotherapy in patients with HCC. Our study suggests that UCK2 could be an ideal target for HCC.

Microstructure Transformation in Laser Additive Manufactured NiTi Alloy with Quasi-In-Situ Compression.

For NiTi alloys, different additive manufacturing processes may have different compressive recovery capabilities. In particular, there are relatively few studies on the compressive recovery ability of NiTi alloys by the laser-directed energy deposition (LDED) process. In this paper, the compression recovery properties of NiTi alloys with the LDED process were investigated quasi-in-situ by means of transmission electron microscopy, an electron backscatter diffractometer, and focused ion beam-fixed-point sample preparation. The results showed that the material can be completely recovered under 4% deformation and the B19' martensite phase content and dislocation density are basically unchanged. However, the recovery rate was only 90% and the unrecoverable strain was 0.86% at 8% deformation. Meanwhile, the B19' martensite phase content and dislocation density of the material increased. Furthermore, with the increase in deformation, the relative dislocation pinning effect of the Ti2Ni precipitated phase in the alloy was enhanced, which reduced the compressive strain recovery to a certain extent.

Impact of Job Satisfaction and Social Support on Job Performance Among Primary Care Providers in Northeast China: A Cross-Sectional Study.

Background: Primary health care institutions face major challenges in maintaining the accessibility and affordability of health services. This requires primary care providers to change and improve their performance. Therefore, Study on the job performance is conducive to improve the quality of primary health care services and the sense of access of primary care providers.To understand the current status of job performance among primary care providers in Heilongjiang Province, China, and explore the impact of job satisfaction and social support on job performance, further to improve the job performance of primary care providers and ensure the stable development of primary health services. Methods: A stratified sampling method was adopted to select 1,500 primary care providers from seven cities in Heilongjiang Province, China, using the gross domestic product development level of each city as a basis. A questionnaire survey was conducted (effective response rate was 85.8%) by using sociodemographic factors, job satisfaction scale, social support scale and job performance scale. One-way ANOVA or independent sample t-test was used to analyze the differences of demographic factors on job performance. Pearson correlation analysis was used to measure relationship between job satisfaction, social support and job performance. Hierarchical linear regression was used to analyze the relevant influencing factors associated with job performance among primary care providers. Results: Among the primary care providers who participated in this survey, the mean job performance score was 22.189 (SD = 7.695). The job performance of primary care providers was positively correlated with job satisfaction (r=0.574, p < 0.001), and was also positively correlated with social support (r = 0.534, p < 0.001). Model 3 showed that job satisfaction (ß = 0.299, p < 0.001) and social support (ß = 0.149, p <0.001) are positive predictors of job performance, respectively. Moreover, the regression relationship explained that 37.6% for the variation of the dependent variable. Conclusions: The job performance of primary care providers in Heilongjiang province is relatively low. Job satisfaction and social support are the relevant factors affecting the job performance of primary care providers. It is necessary to provide assistance to primary care providers in terms of family, organization, society, policy, etc., to improve their job performance, and to better provide high-quality health services to the grassroots.

The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System.

Drug delivery system (DDS) realizes the drug delivery process through the drug carrier. As an important part of DDS, the selection of the drug carrier material is extremely critical, which requires the carrier material to possess excellent biocompatibility and targeting and not affect the pharmacological action of the drug. As one of the endogenous extracellular vesicles, exosomes are 30-100 nm in diameter, which are considered a new generation of a natural nanoscale delivery system. Exosomes secreted by different types of cells carry signaling molecules (such as proteins and nucleic acid) playing an important role in cell behaviors. Owing to their ability to specialize in intercellular communication, exosomes provide a distinctive method to deliver therapeutic drugs to target cells. In this concept, exosomes as the natural liposomes carry endogenous biomolecules, have excellent biocompatibility, and could be loaded with cargo both in vivo and in vitro. In addition, modifications by genetic and/or chemical engineering to part of the exosome surface or complement the desired natural effect may enhance the targeting with drug loading capability. Notably, exosomes weakly react with serum proteins prolonging cargo half-life. Overall, exosomes as natural carriers integrate the superiority of synthetic nanocarriers and cellular communication while precluding their limitations, which provides novel and reliable methods for drug delivery and treatment. Our review focuses on the therapeutic potentials and clinical values of exosomes as a carrier of drug delivery system in multiple diseases, including cancer, nervous, immune, and skeletal system diseases.

Clinical Efficacy and Safety Study of Mifepristone with Misoprostol Treatment in Patients with Missed Abortion.

Currently, medication abortion is widely used in clinical practice in China. The aim of this study was to investigate the effect of mifepristone with misoprostol treatment on the efficacy of patients with missed abortion (MA) and the safety of this drug regimen. 95 patients with MA treated in our hospital from February 2019 to April 2021 were collected as the subjects of this study, and the patients were divided into the control and the research groups according to different treatment modalities. Among them, 46 cases in the control group were treated by diethylstilbestrol combined with oxytocin and 49 cases in the research group were treated by mifepristone combined with misoprostol, and both groups underwent curettage after medication. The rates of complete abortion, time of embryo expulsion, time of operation, intraoperative bleeding, time of postoperative vaginal bleeding, amount of vaginal bleeding, rate of one-time curettage, the levels of serum estradiol (E2), progesterone (P), ß-chorionic gonadotropin (ß-hCG), and interleukin-18 (IL-18), and the incidence of adverse effects in the two groups were examined and compared. Alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (Scr) were used as indicators to evaluate the safety of the drug. The results showed that the rates of complete abortion and one-time curettage were significantly higher in the study group than in the control group, while the time of embryo expulsion, operation time, intraoperative bleeding, postoperative vaginal bleeding time, and vaginal bleeding were significantly lower than in the control group. The serum E2, P, and ß-hCG levels before curettage in both groups were significantly higher, and IL-18 levels were significantly lower than those at the time of admission, with E2, P, and ß-hCG levels increasing more and IL-18 levels decreasing more in the research group. After drug treatment, no abnormal changes in liver and kidney functions were observed in both groups, and the incidence of adverse reactions was at a similar and lower level in both groups. This shows that mifepristone with misoprostol is a safer and more effective drug regimen for the treatment of MA, which can regulate the levels of serum sex hormones and inflammatory factors in the body, promote the shedding of placental tissue, and create conditions for improving the rate of curettage.

Anthropometric accuracy of three-dimensional average faces compared to conventional facial measurements.

This study aimed to evaluate and compare the accuracy of average faces constructed by different methods. Original three-dimensional facial images of 26 adults in Chinese ethnicity were imported into Di3DView and MorphAnalyser for image processing. Six average faces (Ave_D15, Ave_D24, Ave_MG15, Ave_MG24, Ave_MO15, Ave_MO24) were constructed using "surface-based registration" method with different number of landmarks and template meshes. Topographic analysis was performed, and the accuracy of six average faces was assessed by linear and angular parameters in correspondence with arithmetic means calculated from individual original images. Among the six average faces constructed by the two systems, Ave_MG15 had the highest accuracy in comparison with the conventional method, while Ave_D15 had the least accuracy. Other average faces were comparable regarding the number of discrepant parameters with clinical significance. However, marginal and non-registered areas were the most inaccurate regions using Di3DView. For MorphAnalyser, the type of template mesh had an effect on the accuracy of the final 3D average face, but additional landmarks did not improve the accuracy. This study highlights the importance of validating software packages and determining the degree of accuracy, as well as the variables which may affect the result.

A novel mitochondrial amidoxime reducing component 2 is a favorable indicator of cancer and suppresses the progression of hepatocellular carcinoma by regulating the expression of p27.

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality in the United States. Exploring the mechanism of HCC and identifying ideal targets is critical. In the present study, we demonstrated metabolism dysfunction might be a key diver for the development of HCC. The mitochondrial amidoxime reducing component 2 (MARC2) as a newly discovered molybdenum enzyme was downregulated in human HCC tissues and HCC cells. Downregulated MARC2 was significantly associated with clinicopathological characteristics of HCC, such as tumor size, AFP levels, and tumor grade and was an independent risk factor of poor prognosis. Both in vitro and in vivo studies suggested that MARC2 suppressed the progression of HCC by regulating the protein expression level of p27. The Hippo signaling pathway and RNF123 were required for this process. Moreover, MARC2 regulated expression of HNF4A via the Hippo signaling pathway. HNF4A was recruited to the promoter of MARC2 forming a feedback loop. MARC2 levels were downregulated by methylation. We demonstrated the prognostic value of MARC2 in HCC and determined the mechanism by which MARC2 suppressed the progression of HCC in this study. These findings may lead to new therapeutic targets for HCC.

ABCA8 is regulated by miR-374b-5p and inhibits proliferation and metastasis of hepatocellular carcinoma through the ERK/ZEB1 pathway.

BACKGROUND: ATP binding cassette subfamily A member 8 (ABCA8) belongs to the ATP binding cassette (ABC) transporter superfamily. ABCA8 is a transmembrane transporter responsible for the transport of organics, such as cholesterol, and drug efflux. Some members of the ABC subfamily, such as ABCA1, may inhibit cancer development. However, the mechanism of ABCA8 in the process of cancer activation is still ambiguous. METHODS: The expression of ABCA8 in human hepatocellular carcinoma (HCC) tissues and cell lines was examined using qPCR, immunoblotting, and immunohistochemical staining. The effects of ABCA8 on the proliferation and metastasis of HCC were examined using in vitro and in vivo functional tests. A luciferase reporter assay was performed to explore the binding between microRNA-374b-5p (miR-374b-5p) and the ABCA8 3'-untranslated region (UTR). RESULTS: ABCA8 was frequently down-regulated in HCC and this down-regulation was negatively correlated with prognosis. The overexpression of ABCA8 inhibited growth and metastasis in HCC, whereas the knockdown of ABCA8 exerted the antithetical effects both in vivo and in vitro. ABCA8 was down-regulated by miR-374b-5p; this down-regulation can induce epithelial transformation to mesenchyme via the ERK/ZEB1 signaling pathway and promote HCC progression. CONCLUSION: We exposed the prognostic value of ABCA8 in HCC, and illuminated a novel pathway in ABCA8-regulated inhibition of HCC tumorigenesis and metastasis. These findings may lead to a new targeted therapy for HCC through the regulation of ABCA8, and miR-374b-5p.

DGaze: CNN-Based Gaze Prediction in Dynamic Scenes.

We conduct novel analyses of users' gaze behaviors in dynamic virtual scenes and, based on our analyses, we present a novel CNN-based model called DGaze for gaze prediction in HMD-based applications. We first collect 43 users' eye tracking data in 5 dynamic scenes under free-viewing conditions. Next, we perform statistical analysis of our data and observe that dynamic object positions, head rotation velocities, and salient regions are correlated with users' gaze positions. Based on our analysis, we present a CNN-based model (DGaze) that combines object position sequence, head velocity sequence, and saliency features to predict users' gaze positions. Our model can be applied to predict not only realtime gaze positions but also gaze positions in the near future and can achieve better performance than prior method. In terms of realtime prediction, DGaze achieves a 22.0% improvement over prior method in dynamic scenes and obtains an improvement of 9.5% in static scenes, based on using the angular distance as the evaluation metric. We also propose a variant of our model called DGaze_ET that can be used to predict future gaze positions with higher precision by combining accurate past gaze data gathered using an eye tracker. We further analyze our CNN architecture and verify the effectiveness of each component in our model. We apply DGaze to gaze-contingent rendering and a game, and also present the evaluation results from a user study.

NCAPG2 overexpression promotes hepatocellular carcinoma proliferation and metastasis through activating the STAT3 and NF-κB/miR-188-3p pathways.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly fatal malignant cancer worldwide. Elucidating the underlying molecular mechanism of HCC progression is critical for the identification of new therapeutic targets for HCC. This study aimed to determine the role of Non-SMC condensin II complex subunit G2 (NCAPG2) in HCC proliferation and metastasis. METHODS: We detected NCAPG2 expression in tissues using immunohistochemistry, western blotting and real-time PCR. The effects of NCAPG2 on cell proliferation and metastasis were evaluated both in vitro and in vivo. Immunocytochemistry, enzyme linked immunosorbent assay, co-immunoprecipitation and luciferase reporter assay were performed to uncover the underlying mechanisms. FINDINGS: We found that NCAPG2 is frequently upregulated in HCC tumour tissues and predicts a poor prognosis. NCAPG2 overexpression promotes HCC proliferation, migration, and invasion through activating STAT3 and NF-κB signalling pathways. Moreover, NCAPG2 is a direct target of miR-188-3p. We demonstrated the existence of a positive feedback loop between NCAPG2 and p-STAT3 and a negative feedback loop between NCAPG2 and miR-188-3p. INTERPRETATION: Our study indicates that NCAPG2 overexpression could drive HCC proliferation and metastasis through activation of the STAT3 and NF-κB/miR-188-3p pathways. These findings may contribute to the identification of novel biomarkers and therapeutic targets for HCC. FUND: National Key Program for Science and Technology Research and Development (Grant No. 2016YFC0905902); the National Natural Scientific Foundation of China (Nos. 81772588, 81602058, 81773194); University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province (Grant No. UNPYSCT-2016200); the Innovative Research Program for Graduate of Harbin Medical University (Grant Nos. YJSCX2017-38HYD, YJSCX2016-18HYD).

SGaze: A Data-Driven Eye-Head Coordination Model for Realtime Gaze Prediction.

We present a novel, data-driven eye-head coordination model that can be used for realtime gaze prediction for immersive HMD-based applications without any external hardware or eye tracker. Our model (SGaze) is computed by generating a large dataset that corresponds to different users navigating in virtual worlds with different lighting conditions. We perform statistical analysis on the recorded data and observe a linear correlation between gaze positions and head rotation angular velocities. We also find that there exists a latency between eye movements and head movements. SGaze can work as a software-based realtime gaze predictor and we formulate a time related function between head movement and eye movement and use that for realtime gaze position prediction. We demonstrate the benefits of SGaze for gaze-contingent rendering and evaluate the results with a user study.